Heather Boerner

More than half of people living with HIV and suppressed viral loads nonetheless had imaging-confirmed coronary artery disease – and despite longtime use of HIV drugs that have been associated with cardiovascular trouble, none of those drugs were implicated in disease risk in this study.

“Traditional risk factors and duration of HIV infection were associated with severe coronary artery disease,” said Andreas Knudsen, MD, PhD, an infectious disease provider at Copenhagen University Hospital, Hvidovre, Denmark, during his presentation at the 18th European AIDS Conference. “When we adjusted for time since diagnosis of HIV, none of the drugs remained associated with the severity of coronary artery disease.”

Notably, that included abacavir, which was found in another EACS presentation and in past research to be associated with increased rates of heart attacks. Abacavir is sold individually as a generic as well as a component of Epzicom (abacavir/lamivudine) and the single-drug regimen Triumeq (dolutegravir/abacavir/lamivudine).

The Copenhagen Comorbidity in HIV Infection (COCOMO) study enrolled 1,099 people living with HIV in the Danish capital beginning in 2015, and 705 of them had angiographies via CT available to include in the results. The participants were almost all male (89%), at a healthy weight (BMI of 25), and 96% had undetectable viral loads.

Large minorities of participants also had traditional risk factors for coronary artery disease. More than one in four smoked, one in five had high cholesterol, and 42% had high blood pressure. In addition, many had used drugs that have been associated with cardiovascular trouble, including abacavir, which 26% of participants had used; indinavir, used by 17% of participants; zidovudine/AZT, used by 47%; and didanosine, which 14% used. (While abacavir is still in use, the other three drugs are considered legacy drugs and are not in current use.)

In addition, nearly one in three (29%) were currently using a protease inhibitor, which has been associated with heart failure.

When the investigators looked at participants’ CTs, they found that, by the Coronary Artery Disease-Reporting and Data Systems (CAD-RAMS) scoring system, close to half (46%) had clear arteries with no signs of coronary artery disease. But that also meant that 54% had some blockage or stiffening of the arteries. The good news is that 27% of those people had minimal or mild coronary artery disease.

But a full 17% had confirmed obstructive coronary artery disease, and another 1 in 10 participants had the highest level of blockages. When they broke the data down by traditional and HIV medication–related risk factors for coronary artery disease, they found something interesting. Although obesity was associated with the presence of atherosclerosis, it wasn’t associated with severe disease. But diabetes was the reverse of that: It wasn’t associated with the presence of the disease, but it was associated with more severe disease.

And when they looked at abacavir, they found no relationship between the drug and atherosclerosis. “Abacavir was not associated with the presence of atherosclerosis and was also not associated with severity of disease,” said Dr. Knudsen.

Although past use of AZT, indinavir, and didanosine were associated with severity of atherosclerosis, that association went away when Dr. Knudsen and team adjusted the findings for time since diagnosis. What was associated atherosclerosis was length of time living with HIV itself. For every 5 years a person lived with HIV, the study found the risk of having any atherosclerosis increased 20% and severity increased 23%. In addition, being a man was associated with a nearly 2.5-times increased risk of having any atherosclerosis and a 96% increased chance of having more severe atherosclerosis. Having diabetes was associated with a nearly threefold increased risk of atherosclerosis, as was every additional decade of life for a person who was living with HIV.

The findings confirm the baseline data of the REPRIEVE trial, which recently released data showing similarly high rates of atherosclerotic plaque in people living with HIV who didn’t register as “at risk” for cardiovascular disease using traditional scoring methods.

“It’s important in that it’s a huge study that’s confirmatory [of] what we know, which is that there are high levels of subclinical coronary artery disease in people living with HIV,” said Steven Grinspoon, MD, professor at Harvard Medical School in Boston, Massachusetts, and principal investigator of REPRIEVE.

As for the lack of association between abacavir and cardiovascular risk, he said he’s taking the findings with a grain of salt.

“It’s hard to make a lot out of that,” he said. “It’s hard to know in a cross-sectional study. People put people on different things.”

In Spain, where Jose Ignacio Bernardino, MD, treats people living with HIV at La Paz University Hospital in Madrid, abacavir is mostly a moot point, as clinicians have long since moved away from maintaining people living with HIV on any abacavir-containing regimens. What’s more important in the study, he told this news organization, is that “worrisome” high level of risk. REPRIEVE will test whether statins can reduce heart disease events in people living with HIV. But in the meantime, he said the take-away for clinicians from the study is the primary importance of traditional cardiovascular risk factors.

“We have to acknowledge that the major cardiovascular risk factor is age,” he said. “When patients are approaching their 50s, I usually try to stress a lot about cardiovascular risk factors in general. I stress healthy lifestyle – get physical exercise, hypertension, glucose, lipids – in every single patient.”

Dr. Knudsen and Dr. Bernardino have disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

More than half of people living with HIV and suppressed viral loads nonetheless had imaging-confirmed coronary artery disease – and despite longtime use of HIV drugs that have been associated with cardiovascular trouble, none of those drugs were implicated in disease risk in this study.

“Traditional risk factors and duration of HIV infection were associated with severe coronary artery disease,” said Andreas Knudsen, MD, PhD, an infectious disease provider at Copenhagen University Hospital, Hvidovre, Denmark, during his presentation at the 18th European AIDS Conference. “When we adjusted for time since diagnosis of HIV, none of the drugs remained associated with the severity of coronary artery disease.”

Notably, that included abacavir, which was found in another EACS presentation and in past research to be associated with increased rates of heart attacks. Abacavir is sold individually as a generic as well as a component of Epzicom (abacavir/lamivudine) and the single-drug regimen Triumeq (dolutegravir/abacavir/lamivudine).

The Copenhagen Comorbidity in HIV Infection (COCOMO) study enrolled 1,099 people living with HIV in the Danish capital beginning in 2015, and 705 of them had angiographies via CT available to include in the results. The participants were almost all male (89%), at a healthy weight (BMI of 25), and 96% had undetectable viral loads.

Large minorities of participants also had traditional risk factors for coronary artery disease. More than one in four smoked, one in five had high cholesterol, and 42% had high blood pressure. In addition, many had used drugs that have been associated with cardiovascular trouble, including abacavir, which 26% of participants had used; indinavir, used by 17% of participants; zidovudine/AZT, used by 47%; and didanosine, which 14% used. (While abacavir is still in use, the other three drugs are considered legacy drugs and are not in current use.)

In addition, nearly one in three (29%) were currently using a protease inhibitor, which has been associated with heart failure.

When the investigators looked at participants’ CTs, they found that, by the Coronary Artery Disease-Reporting and Data Systems (CAD-RAMS) scoring system, close to half (46%) had clear arteries with no signs of coronary artery disease. But that also meant that 54% had some blockage or stiffening of the arteries. The good news is that 27% of those people had minimal or mild coronary artery disease.

But a full 17% had confirmed obstructive coronary artery disease, and another 1 in 10 participants had the highest level of blockages. When they broke the data down by traditional and HIV medication–related risk factors for coronary artery disease, they found something interesting. Although obesity was associated with the presence of atherosclerosis, it wasn’t associated with severe disease. But diabetes was the reverse of that: It wasn’t associated with the presence of the disease, but it was associated with more severe disease.

And when they looked at abacavir, they found no relationship between the drug and atherosclerosis. “Abacavir was not associated with the presence of atherosclerosis and was also not associated with severity of disease,” said Dr. Knudsen.

Although past use of AZT, indinavir, and didanosine were associated with severity of atherosclerosis, that association went away when Dr. Knudsen and team adjusted the findings for time since diagnosis. What was associated atherosclerosis was length of time living with HIV itself. For every 5 years a person lived with HIV, the study found the risk of having any atherosclerosis increased 20% and severity increased 23%. In addition, being a man was associated with a nearly 2.5-times increased risk of having any atherosclerosis and a 96% increased chance of having more severe atherosclerosis. Having diabetes was associated with a nearly threefold increased risk of atherosclerosis, as was every additional decade of life for a person who was living with HIV.

The findings confirm the baseline data of the REPRIEVE trial, which recently released data showing similarly high rates of atherosclerotic plaque in people living with HIV who didn’t register as “at risk” for cardiovascular disease using traditional scoring methods.

“It’s important in that it’s a huge study that’s confirmatory [of] what we know, which is that there are high levels of subclinical coronary artery disease in people living with HIV,” said Steven Grinspoon, MD, professor at Harvard Medical School in Boston, Massachusetts, and principal investigator of REPRIEVE.

As for the lack of association between abacavir and cardiovascular risk, he said he’s taking the findings with a grain of salt.

“It’s hard to make a lot out of that,” he said. “It’s hard to know in a cross-sectional study. People put people on different things.”

In Spain, where Jose Ignacio Bernardino, MD, treats people living with HIV at La Paz University Hospital in Madrid, abacavir is mostly a moot point, as clinicians have long since moved away from maintaining people living with HIV on any abacavir-containing regimens. What’s more important in the study, he told this news organization, is that “worrisome” high level of risk. REPRIEVE will test whether statins can reduce heart disease events in people living with HIV. But in the meantime, he said the take-away for clinicians from the study is the primary importance of traditional cardiovascular risk factors.

“We have to acknowledge that the major cardiovascular risk factor is age,” he said. “When patients are approaching their 50s, I usually try to stress a lot about cardiovascular risk factors in general. I stress healthy lifestyle – get physical exercise, hypertension, glucose, lipids – in every single patient.”

Dr. Knudsen and Dr. Bernardino have disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

More than half of people living with HIV and suppressed viral loads nonetheless had imaging-confirmed coronary artery disease – and despite longtime use of HIV drugs that have been associated with cardiovascular trouble, none of those drugs were implicated in disease risk in this study.

“Traditional risk factors and duration of HIV infection were associated with severe coronary artery disease,” said Andreas Knudsen, MD, PhD, an infectious disease provider at Copenhagen University Hospital, Hvidovre, Denmark, during his presentation at the 18th European AIDS Conference. “When we adjusted for time since diagnosis of HIV, none of the drugs remained associated with the severity of coronary artery disease.”

Notably, that included abacavir, which was found in another EACS presentation and in past research to be associated with increased rates of heart attacks. Abacavir is sold individually as a generic as well as a component of Epzicom (abacavir/lamivudine) and the single-drug regimen Triumeq (dolutegravir/abacavir/lamivudine).

The Copenhagen Comorbidity in HIV Infection (COCOMO) study enrolled 1,099 people living with HIV in the Danish capital beginning in 2015, and 705 of them had angiographies via CT available to include in the results. The participants were almost all male (89%), at a healthy weight (BMI of 25), and 96% had undetectable viral loads.

Large minorities of participants also had traditional risk factors for coronary artery disease. More than one in four smoked, one in five had high cholesterol, and 42% had high blood pressure. In addition, many had used drugs that have been associated with cardiovascular trouble, including abacavir, which 26% of participants had used; indinavir, used by 17% of participants; zidovudine/AZT, used by 47%; and didanosine, which 14% used. (While abacavir is still in use, the other three drugs are considered legacy drugs and are not in current use.)

In addition, nearly one in three (29%) were currently using a protease inhibitor, which has been associated with heart failure.

When the investigators looked at participants’ CTs, they found that, by the Coronary Artery Disease-Reporting and Data Systems (CAD-RAMS) scoring system, close to half (46%) had clear arteries with no signs of coronary artery disease. But that also meant that 54% had some blockage or stiffening of the arteries. The good news is that 27% of those people had minimal or mild coronary artery disease.

But a full 17% had confirmed obstructive coronary artery disease, and another 1 in 10 participants had the highest level of blockages. When they broke the data down by traditional and HIV medication–related risk factors for coronary artery disease, they found something interesting. Although obesity was associated with the presence of atherosclerosis, it wasn’t associated with severe disease. But diabetes was the reverse of that: It wasn’t associated with the presence of the disease, but it was associated with more severe disease.

And when they looked at abacavir, they found no relationship between the drug and atherosclerosis. “Abacavir was not associated with the presence of atherosclerosis and was also not associated with severity of disease,” said Dr. Knudsen.

Although past use of AZT, indinavir, and didanosine were associated with severity of atherosclerosis, that association went away when Dr. Knudsen and team adjusted the findings for time since diagnosis. What was associated atherosclerosis was length of time living with HIV itself. For every 5 years a person lived with HIV, the study found the risk of having any atherosclerosis increased 20% and severity increased 23%. In addition, being a man was associated with a nearly 2.5-times increased risk of having any atherosclerosis and a 96% increased chance of having more severe atherosclerosis. Having diabetes was associated with a nearly threefold increased risk of atherosclerosis, as was every additional decade of life for a person who was living with HIV.

The findings confirm the baseline data of the REPRIEVE trial, which recently released data showing similarly high rates of atherosclerotic plaque in people living with HIV who didn’t register as “at risk” for cardiovascular disease using traditional scoring methods.

“It’s important in that it’s a huge study that’s confirmatory [of] what we know, which is that there are high levels of subclinical coronary artery disease in people living with HIV,” said Steven Grinspoon, MD, professor at Harvard Medical School in Boston, Massachusetts, and principal investigator of REPRIEVE.

As for the lack of association between abacavir and cardiovascular risk, he said he’s taking the findings with a grain of salt.

“It’s hard to make a lot out of that,” he said. “It’s hard to know in a cross-sectional study. People put people on different things.”

In Spain, where Jose Ignacio Bernardino, MD, treats people living with HIV at La Paz University Hospital in Madrid, abacavir is mostly a moot point, as clinicians have long since moved away from maintaining people living with HIV on any abacavir-containing regimens. What’s more important in the study, he told this news organization, is that “worrisome” high level of risk. REPRIEVE will test whether statins can reduce heart disease events in people living with HIV. But in the meantime, he said the take-away for clinicians from the study is the primary importance of traditional cardiovascular risk factors.

“We have to acknowledge that the major cardiovascular risk factor is age,” he said. “When patients are approaching their 50s, I usually try to stress a lot about cardiovascular risk factors in general. I stress healthy lifestyle – get physical exercise, hypertension, glucose, lipids – in every single patient.”

Dr. Knudsen and Dr. Bernardino have disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

The MAVMET study, the first randomized controlled trial of maraviroc (Selzentry) with or without metformin, failed to reduce liver fat in people living with HIV and nonalcoholic fatty liver disease compared with placebo – and in some cases, prolonged use actually increased liver fat.

And that means clinicians like Yvonne Gilleece, MB BCh, who was not involved in the study but does run a liver clinic in England for people living with HIV, are returning to the one intervention proven to work. “As yet, the only thing that is proven to have a very positive effect that is published is weight loss,” said Dr. Gilleece, who runs the clinic at Brighton and Sussex University Hospital. “You don’t put someone on these particular drugs, particularly this combination, easily. MAVMET has really demonstrated that, actually, it’s not effective, and it’s not particularly beneficial to patients.”

The MAVMET trial data was presented at the 18th European AIDS Conference,

There was good reason to think maraviroc might work. A 2018 study in the journal Hepatology found that one of maraviroc’s molecular cousins, cenicriviroc, significantly reduced fibrosis in people with NAFLD. Dr. Gilleece is co-investigator of another study of maraviroc in NAFLD, the HEPMARC trial, which is wrapping up now. In addition to those studies, there are other potential treatments in ongoing trials, including semaglutide, which is being studied in the United States under the study name SLIM LIVER.

MAVMET enrolled 90 people living with HIV from six clinical sites in London who were 35 or older and who had at least one marker for NAFLD, such as abnormal liver lab results. But 70% qualified via imaging- and/or biopsy-confirmed NAFLD. Almost all participants (93%) were men and 81% were White. The trial excluded people who were pregnant or breastfeeding. The median age was 52, and the participants met the criteria for overweight but not obesity, with a median BMI of 28.

In other words, participants generally had fatty livers without the inflammation that characterizes the more aggressive nonalcoholic steatohepatitis (NASH). Clinicians can’t yet differentiate between those who will continue to have asymptomatic fatty liver and those who will progress to NASH and potentially need a liver transplant.

All people living with HIV in the trial had undetectable viral loads and were on HIV treatment. Nearly 1 in 5 (19%) were using a treatment regimen containing tenofovir alafenamide (TAF), which has been associated with weight gain. Nearly half were on integrase strand inhibitors.

Investigators divided the participants up into four groups: 24 people stayed on their HIV treatment and added nothing else; 23 people took maraviroc only; 21 took metformin only; and the final group took both maraviroc and metformin. Across groups, liver fat at baseline was 8.9%, and 78% had mild hepatic steatosis.

After taking the medications for 48 weeks, participants returned to clinic to be scanned via MRI proton density fat fraction (MRI-PDFF), which has been found to successfully measure liver fat. However, because of the COVID-19 pandemic, 20 of the 83 people who returned to the clinic came later than 48 weeks after the trial began.

When investigators looked at the results, they didn’t see what they hypothesized, said Sarah Pett, professor of infectious diseases at University College, London: The scatter plot graph of change in weight looked, well, scattershot: People who didn’t take any additional treatment sometimes lost more liver fat than those on treatment. In fact, the mean liver fat percentage rose by 2.2% in the maraviroc group, 1.3% in the metformin group, and 0.8% in the combination group. The control group saw an increase of 1.4% – meaning that there was no difference between the change in fat between those on treatment and those not.

What’s more, those who had delayed scans – and stayed on their treatment for a median of an additional 16 weeks – saw their liver fat increase even more.

In an interview, Dr. Pett called the results “disappointing.” “The numbers are quite small, but we still didn’t expect this,” she said. “It’s not explained by lockdown weight gain, although we still have to look in detail at how alcohol consumption could have contributed.”

There were also some limits to what the design of this particular trial could tell the researchers. For instance, nearly half of the participants in the maraviroc group, a third of the people in the metformin group, and 36% of those in the combination group had hepatic steatosis grades of 0, meaning that their livers were healthy. And MRI-PDFF becomes less reliable at that level.

“One of the regrets is that perhaps we should have done FibroScan [ultrasound], as well,” Dr. Pett said. The consequence is that the study may have undercounted the fat level by using MRI-PFDD.

“This suggests that the surrogate markers of NAFLD used in MAVMET were not very sensitive to those with a higher percentage of fat,” Dr. Pett said during her presentation. “We were really trying to be pragmatic and not require an MRI at screening.”

Whatever the case, she said that the failure of this particular treatment just highlights the growing need to look more seriously, and more collaboratively, at fat and liver health in people living with HIV.

“We need to really focus on setting up large cohorts of people living with HIV to look in a rigorous way at weight gain, changes in waist circumference, ectopic fat, capture fatty liver disease index scores, and cardiovascular risk, to acquire some longitudinal data,” she said. “And [we need to] join with our fellow researchers in overweight and obesity medicine and hepatology to make sure that people living with HIV are included in new treatments for NASH, as several large RCTs have excluded [people living with HIV].”

From Dr. Gilleece’s perspective, it also just speaks to how far the field has to go in identifying those with asymptomatic fatty livers from those who will progress to fibrosis and potentially need liver transplants.

“MAVMET shows the difficulty in managing NAFLD,” she said. “It seems quite an innocuous disease, because for the majority of people it’s not going to cause a problem in their lifetime. But the reality is, for some it will, and we don’t really know how to treat it.”

Dr. Gilleece has disclosed no relevant financial relationships. Dr. Pett reported receiving funding for trials from Gilead Sciences and Janssen-Cilag. ViiV Healthcare funded the MAVMET trial.

A version of this article first appeared on Medscape.com.

The MAVMET study, the first randomized controlled trial of maraviroc (Selzentry) with or without metformin, failed to reduce liver fat in people living with HIV and nonalcoholic fatty liver disease compared with placebo – and in some cases, prolonged use actually increased liver fat.

And that means clinicians like Yvonne Gilleece, MB BCh, who was not involved in the study but does run a liver clinic in England for people living with HIV, are returning to the one intervention proven to work. “As yet, the only thing that is proven to have a very positive effect that is published is weight loss,” said Dr. Gilleece, who runs the clinic at Brighton and Sussex University Hospital. “You don’t put someone on these particular drugs, particularly this combination, easily. MAVMET has really demonstrated that, actually, it’s not effective, and it’s not particularly beneficial to patients.”

The MAVMET trial data was presented at the 18th European AIDS Conference,

There was good reason to think maraviroc might work. A 2018 study in the journal Hepatology found that one of maraviroc’s molecular cousins, cenicriviroc, significantly reduced fibrosis in people with NAFLD. Dr. Gilleece is co-investigator of another study of maraviroc in NAFLD, the HEPMARC trial, which is wrapping up now. In addition to those studies, there are other potential treatments in ongoing trials, including semaglutide, which is being studied in the United States under the study name SLIM LIVER.

MAVMET enrolled 90 people living with HIV from six clinical sites in London who were 35 or older and who had at least one marker for NAFLD, such as abnormal liver lab results. But 70% qualified via imaging- and/or biopsy-confirmed NAFLD. Almost all participants (93%) were men and 81% were White. The trial excluded people who were pregnant or breastfeeding. The median age was 52, and the participants met the criteria for overweight but not obesity, with a median BMI of 28.

In other words, participants generally had fatty livers without the inflammation that characterizes the more aggressive nonalcoholic steatohepatitis (NASH). Clinicians can’t yet differentiate between those who will continue to have asymptomatic fatty liver and those who will progress to NASH and potentially need a liver transplant.

All people living with HIV in the trial had undetectable viral loads and were on HIV treatment. Nearly 1 in 5 (19%) were using a treatment regimen containing tenofovir alafenamide (TAF), which has been associated with weight gain. Nearly half were on integrase strand inhibitors.

Investigators divided the participants up into four groups: 24 people stayed on their HIV treatment and added nothing else; 23 people took maraviroc only; 21 took metformin only; and the final group took both maraviroc and metformin. Across groups, liver fat at baseline was 8.9%, and 78% had mild hepatic steatosis.

After taking the medications for 48 weeks, participants returned to clinic to be scanned via MRI proton density fat fraction (MRI-PDFF), which has been found to successfully measure liver fat. However, because of the COVID-19 pandemic, 20 of the 83 people who returned to the clinic came later than 48 weeks after the trial began.

When investigators looked at the results, they didn’t see what they hypothesized, said Sarah Pett, professor of infectious diseases at University College, London: The scatter plot graph of change in weight looked, well, scattershot: People who didn’t take any additional treatment sometimes lost more liver fat than those on treatment. In fact, the mean liver fat percentage rose by 2.2% in the maraviroc group, 1.3% in the metformin group, and 0.8% in the combination group. The control group saw an increase of 1.4% – meaning that there was no difference between the change in fat between those on treatment and those not.

What’s more, those who had delayed scans – and stayed on their treatment for a median of an additional 16 weeks – saw their liver fat increase even more.

In an interview, Dr. Pett called the results “disappointing.” “The numbers are quite small, but we still didn’t expect this,” she said. “It’s not explained by lockdown weight gain, although we still have to look in detail at how alcohol consumption could have contributed.”

There were also some limits to what the design of this particular trial could tell the researchers. For instance, nearly half of the participants in the maraviroc group, a third of the people in the metformin group, and 36% of those in the combination group had hepatic steatosis grades of 0, meaning that their livers were healthy. And MRI-PDFF becomes less reliable at that level.

“One of the regrets is that perhaps we should have done FibroScan [ultrasound], as well,” Dr. Pett said. The consequence is that the study may have undercounted the fat level by using MRI-PFDD.

“This suggests that the surrogate markers of NAFLD used in MAVMET were not very sensitive to those with a higher percentage of fat,” Dr. Pett said during her presentation. “We were really trying to be pragmatic and not require an MRI at screening.”

Whatever the case, she said that the failure of this particular treatment just highlights the growing need to look more seriously, and more collaboratively, at fat and liver health in people living with HIV.

“We need to really focus on setting up large cohorts of people living with HIV to look in a rigorous way at weight gain, changes in waist circumference, ectopic fat, capture fatty liver disease index scores, and cardiovascular risk, to acquire some longitudinal data,” she said. “And [we need to] join with our fellow researchers in overweight and obesity medicine and hepatology to make sure that people living with HIV are included in new treatments for NASH, as several large RCTs have excluded [people living with HIV].”

From Dr. Gilleece’s perspective, it also just speaks to how far the field has to go in identifying those with asymptomatic fatty livers from those who will progress to fibrosis and potentially need liver transplants.

“MAVMET shows the difficulty in managing NAFLD,” she said. “It seems quite an innocuous disease, because for the majority of people it’s not going to cause a problem in their lifetime. But the reality is, for some it will, and we don’t really know how to treat it.”

Dr. Gilleece has disclosed no relevant financial relationships. Dr. Pett reported receiving funding for trials from Gilead Sciences and Janssen-Cilag. ViiV Healthcare funded the MAVMET trial.

A version of this article first appeared on Medscape.com.

The MAVMET study, the first randomized controlled trial of maraviroc (Selzentry) with or without metformin, failed to reduce liver fat in people living with HIV and nonalcoholic fatty liver disease compared with placebo – and in some cases, prolonged use actually increased liver fat.

And that means clinicians like Yvonne Gilleece, MB BCh, who was not involved in the study but does run a liver clinic in England for people living with HIV, are returning to the one intervention proven to work. “As yet, the only thing that is proven to have a very positive effect that is published is weight loss,” said Dr. Gilleece, who runs the clinic at Brighton and Sussex University Hospital. “You don’t put someone on these particular drugs, particularly this combination, easily. MAVMET has really demonstrated that, actually, it’s not effective, and it’s not particularly beneficial to patients.”

The MAVMET trial data was presented at the 18th European AIDS Conference,

There was good reason to think maraviroc might work. A 2018 study in the journal Hepatology found that one of maraviroc’s molecular cousins, cenicriviroc, significantly reduced fibrosis in people with NAFLD. Dr. Gilleece is co-investigator of another study of maraviroc in NAFLD, the HEPMARC trial, which is wrapping up now. In addition to those studies, there are other potential treatments in ongoing trials, including semaglutide, which is being studied in the United States under the study name SLIM LIVER.

MAVMET enrolled 90 people living with HIV from six clinical sites in London who were 35 or older and who had at least one marker for NAFLD, such as abnormal liver lab results. But 70% qualified via imaging- and/or biopsy-confirmed NAFLD. Almost all participants (93%) were men and 81% were White. The trial excluded people who were pregnant or breastfeeding. The median age was 52, and the participants met the criteria for overweight but not obesity, with a median BMI of 28.

In other words, participants generally had fatty livers without the inflammation that characterizes the more aggressive nonalcoholic steatohepatitis (NASH). Clinicians can’t yet differentiate between those who will continue to have asymptomatic fatty liver and those who will progress to NASH and potentially need a liver transplant.

All people living with HIV in the trial had undetectable viral loads and were on HIV treatment. Nearly 1 in 5 (19%) were using a treatment regimen containing tenofovir alafenamide (TAF), which has been associated with weight gain. Nearly half were on integrase strand inhibitors.

Investigators divided the participants up into four groups: 24 people stayed on their HIV treatment and added nothing else; 23 people took maraviroc only; 21 took metformin only; and the final group took both maraviroc and metformin. Across groups, liver fat at baseline was 8.9%, and 78% had mild hepatic steatosis.

After taking the medications for 48 weeks, participants returned to clinic to be scanned via MRI proton density fat fraction (MRI-PDFF), which has been found to successfully measure liver fat. However, because of the COVID-19 pandemic, 20 of the 83 people who returned to the clinic came later than 48 weeks after the trial began.

When investigators looked at the results, they didn’t see what they hypothesized, said Sarah Pett, professor of infectious diseases at University College, London: The scatter plot graph of change in weight looked, well, scattershot: People who didn’t take any additional treatment sometimes lost more liver fat than those on treatment. In fact, the mean liver fat percentage rose by 2.2% in the maraviroc group, 1.3% in the metformin group, and 0.8% in the combination group. The control group saw an increase of 1.4% – meaning that there was no difference between the change in fat between those on treatment and those not.

What’s more, those who had delayed scans – and stayed on their treatment for a median of an additional 16 weeks – saw their liver fat increase even more.

In an interview, Dr. Pett called the results “disappointing.” “The numbers are quite small, but we still didn’t expect this,” she said. “It’s not explained by lockdown weight gain, although we still have to look in detail at how alcohol consumption could have contributed.”

There were also some limits to what the design of this particular trial could tell the researchers. For instance, nearly half of the participants in the maraviroc group, a third of the people in the metformin group, and 36% of those in the combination group had hepatic steatosis grades of 0, meaning that their livers were healthy. And MRI-PDFF becomes less reliable at that level.

“One of the regrets is that perhaps we should have done FibroScan [ultrasound], as well,” Dr. Pett said. The consequence is that the study may have undercounted the fat level by using MRI-PFDD.

“This suggests that the surrogate markers of NAFLD used in MAVMET were not very sensitive to those with a higher percentage of fat,” Dr. Pett said during her presentation. “We were really trying to be pragmatic and not require an MRI at screening.”

Whatever the case, she said that the failure of this particular treatment just highlights the growing need to look more seriously, and more collaboratively, at fat and liver health in people living with HIV.

“We need to really focus on setting up large cohorts of people living with HIV to look in a rigorous way at weight gain, changes in waist circumference, ectopic fat, capture fatty liver disease index scores, and cardiovascular risk, to acquire some longitudinal data,” she said. “And [we need to] join with our fellow researchers in overweight and obesity medicine and hepatology to make sure that people living with HIV are included in new treatments for NASH, as several large RCTs have excluded [people living with HIV].”

From Dr. Gilleece’s perspective, it also just speaks to how far the field has to go in identifying those with asymptomatic fatty livers from those who will progress to fibrosis and potentially need liver transplants.

“MAVMET shows the difficulty in managing NAFLD,” she said. “It seems quite an innocuous disease, because for the majority of people it’s not going to cause a problem in their lifetime. But the reality is, for some it will, and we don’t really know how to treat it.”

Dr. Gilleece has disclosed no relevant financial relationships. Dr. Pett reported receiving funding for trials from Gilead Sciences and Janssen-Cilag. ViiV Healthcare funded the MAVMET trial.

A version of this article first appeared on Medscape.com.

Nearly one in three gay and bisexual men who were diagnosed with HIV at U.K. sexual health clinics didn’t meet the criteria for “high risk” that would signal to a clinician that they would be good candidates for pre-exposure prophylaxis (PrEP).

And that means that people who appear lower risk may still be good candidates for the HIV prevention pills, said Ann Sullivan, MD, consulting physician at Chelsea and Westminster Hospital, London.

“If people are coming forward for PrEP, they have self-identified that they need PrEP, [and] we should be allowing them to take PrEP,” said Dr. Sullivan at the 18th European AIDS Society Conference (EACS 2021). “We just need to trust patients. People know their risk, and we just have to accept that they know what they need best.”

And while this trial was made up of 95% gay and bisexual men, that ethos applies to every other group that could benefit from PrEP, including cisgender and transgender women and other gender-diverse people, Latinos, and Black Americans. In the United States, these groups make up nearly half of those who could benefit from PrEP under older guidelines but account for just 8% of people currently taking PrEP.

The finding also reinforces growing calls from health care providers to reduce gatekeeping around PrEP. For instance, there’s a move underway by the U.S. Centers for Disease Control and Prevention, where drafts of updated PrEP guidelines call for clinicians to talk to any sexually active teenager and adult about PrEP.

For the PrEP Impact trial, gay and bisexual men who received sexual health care at UK National Health Service sexual health clinics were invited to enroll in the study based on national PrEP guidelines. Those guidelines included being a cisgender man who had had sex with men not currently living with HIV and reporting condomless anal sex in the last 3 months; having a male partner whose HIV status they don’t know or who doesn’t have an undetectable viral load and with whom they’ve had condomless anal sex; or someone who doesn’t reach those criteria but whom the clinician thinks would be a good candidate.

Between Oct. 2017 and Feb. 2020, a total of 17,770 gay and bisexual men and 503 transgender or nonbinary people enrolled in the trial and were paired with 97,098 gay and bisexual men who didn’t use PrEP. (Data from the transgender participants were reported in a separate presentation.) The median age was 27 years, with 14.4% of the cisgender gay men between the ages of 16 and 24. Three out of four cis men were White, most lived in London, and more than half came from very-low-income neighborhoods.

Participants and controls were assessed for whether they were at particularly high risk for acquiring HIV, such as having used PrEP, having had two or more HIV tests, having had a rectal bacterial sexually transmitted infection (STI), or having had contact with someone with HIV or syphilis.

At the end of Feb. 2020, 24 cisgender men on PrEP had acquired HIV compared with 670 in the control group – an 87% reduction in HIV acquisition. Only one of those 24 cis men had lab-confirmed high adherence to PrEP. However, because the hair samples used to judge drug concentration weren’t long enough, Dr. Sullivan and colleagues were unable to assess whether the person really was fully adherent to treatment for the length of the trial.

But when they looked at the assessed behavior of people who acquired HIV, the two groups diverged. While a full 92% of people using PrEP had had STI diagnoses and other markers of increased risk, that was true for only 71% of people not taking PrEP. That meant, Dr. Sullivan said in an interview, that screening guidelines for PrEP were missing 29% of people with low assessed risk for HIV who nevertheless acquired the virus.

The findings led Antonio Urbina, MD, who both prescribes PrEP and manages Mount Sinai Medical Center’s PrEP program in New York, to the same conclusion that Dr. Sullivan and her team came to: that no screener is going to account for everything, and that there may be things that patients don’t want to tell their clinicians about their risk, either because of their own internalized stigma or their calculation that they aren’t comfortable enough with their providers to be honest.

“It reinforces to me that I need to ask more open-ended questions regarding risk and then just talk more about PrEP,” said Dr. Urbina, professor of medicine at Icahn School of Medicine. “Risk is dynamic and changes. And the great thing about PrEP is that if the risk goes up or down, if you have PrEP on board, you maintain this protection against HIV.”

An accompanying presentation on the transgender and nonbinary participants in the Impact Trial found that just one of 503 PrEP users acquired HIV. But here, too, there were people who could have benefited from PrEP but didn’t take it: Of the 477 trans and nonbinary participants who acted as controls, 97 were eligible by current guidelines but didn’t take PrEP. One in four of those declined the offer to take PrEP; the rest weren’t able to take it because they lived outside the treatment area. That, combined with a significantly lower likelihood that Black trans and nonbinary people took PrEP, indicated that work needs to be done to address the needs of people geographically and ethnically.

The data on gay men also raised the “who’s left out” issue for Gina Simoncini, MD, medical director for the Philadelphia AIDS Healthcare Foundation Healthcare Center. Dr. Simoncini previously taught attending physicians at Temple University how to prescribe PrEP and has done many grand rounds for primary care providers on how to manage PrEP.

“My biggest issue with this data is: What about the people who aren’t going to sexual health clinics?” she said. “What about the kid who’s 16 and maybe just barely putting his feet into the waters of sex and doesn’t feel quite comfortable going to a sexual health clinic? What about the trans Indian girl who can’t get to sexual health clinics because of family stigma and cultural stigma? The more we move toward primary care, the more people need to get on board with this.”

Dr. Sullivan reports no relevant financial relationships. Dr. Simoncini is an employee of AIDS Healthcare Foundation and has received advisory board fees from ViiV Healthcare. Dr. Urbina sits on the scientific advisory councils for Gilead Sciences, ViiV Healthcare, and Merck.

A version of this article first appeared on Medscape.com.

Nearly one in three gay and bisexual men who were diagnosed with HIV at U.K. sexual health clinics didn’t meet the criteria for “high risk” that would signal to a clinician that they would be good candidates for pre-exposure prophylaxis (PrEP).

And that means that people who appear lower risk may still be good candidates for the HIV prevention pills, said Ann Sullivan, MD, consulting physician at Chelsea and Westminster Hospital, London.

“If people are coming forward for PrEP, they have self-identified that they need PrEP, [and] we should be allowing them to take PrEP,” said Dr. Sullivan at the 18th European AIDS Society Conference (EACS 2021). “We just need to trust patients. People know their risk, and we just have to accept that they know what they need best.”

And while this trial was made up of 95% gay and bisexual men, that ethos applies to every other group that could benefit from PrEP, including cisgender and transgender women and other gender-diverse people, Latinos, and Black Americans. In the United States, these groups make up nearly half of those who could benefit from PrEP under older guidelines but account for just 8% of people currently taking PrEP.

The finding also reinforces growing calls from health care providers to reduce gatekeeping around PrEP. For instance, there’s a move underway by the U.S. Centers for Disease Control and Prevention, where drafts of updated PrEP guidelines call for clinicians to talk to any sexually active teenager and adult about PrEP.

For the PrEP Impact trial, gay and bisexual men who received sexual health care at UK National Health Service sexual health clinics were invited to enroll in the study based on national PrEP guidelines. Those guidelines included being a cisgender man who had had sex with men not currently living with HIV and reporting condomless anal sex in the last 3 months; having a male partner whose HIV status they don’t know or who doesn’t have an undetectable viral load and with whom they’ve had condomless anal sex; or someone who doesn’t reach those criteria but whom the clinician thinks would be a good candidate.

Between Oct. 2017 and Feb. 2020, a total of 17,770 gay and bisexual men and 503 transgender or nonbinary people enrolled in the trial and were paired with 97,098 gay and bisexual men who didn’t use PrEP. (Data from the transgender participants were reported in a separate presentation.) The median age was 27 years, with 14.4% of the cisgender gay men between the ages of 16 and 24. Three out of four cis men were White, most lived in London, and more than half came from very-low-income neighborhoods.

Participants and controls were assessed for whether they were at particularly high risk for acquiring HIV, such as having used PrEP, having had two or more HIV tests, having had a rectal bacterial sexually transmitted infection (STI), or having had contact with someone with HIV or syphilis.

At the end of Feb. 2020, 24 cisgender men on PrEP had acquired HIV compared with 670 in the control group – an 87% reduction in HIV acquisition. Only one of those 24 cis men had lab-confirmed high adherence to PrEP. However, because the hair samples used to judge drug concentration weren’t long enough, Dr. Sullivan and colleagues were unable to assess whether the person really was fully adherent to treatment for the length of the trial.

But when they looked at the assessed behavior of people who acquired HIV, the two groups diverged. While a full 92% of people using PrEP had had STI diagnoses and other markers of increased risk, that was true for only 71% of people not taking PrEP. That meant, Dr. Sullivan said in an interview, that screening guidelines for PrEP were missing 29% of people with low assessed risk for HIV who nevertheless acquired the virus.

The findings led Antonio Urbina, MD, who both prescribes PrEP and manages Mount Sinai Medical Center’s PrEP program in New York, to the same conclusion that Dr. Sullivan and her team came to: that no screener is going to account for everything, and that there may be things that patients don’t want to tell their clinicians about their risk, either because of their own internalized stigma or their calculation that they aren’t comfortable enough with their providers to be honest.

“It reinforces to me that I need to ask more open-ended questions regarding risk and then just talk more about PrEP,” said Dr. Urbina, professor of medicine at Icahn School of Medicine. “Risk is dynamic and changes. And the great thing about PrEP is that if the risk goes up or down, if you have PrEP on board, you maintain this protection against HIV.”

An accompanying presentation on the transgender and nonbinary participants in the Impact Trial found that just one of 503 PrEP users acquired HIV. But here, too, there were people who could have benefited from PrEP but didn’t take it: Of the 477 trans and nonbinary participants who acted as controls, 97 were eligible by current guidelines but didn’t take PrEP. One in four of those declined the offer to take PrEP; the rest weren’t able to take it because they lived outside the treatment area. That, combined with a significantly lower likelihood that Black trans and nonbinary people took PrEP, indicated that work needs to be done to address the needs of people geographically and ethnically.

The data on gay men also raised the “who’s left out” issue for Gina Simoncini, MD, medical director for the Philadelphia AIDS Healthcare Foundation Healthcare Center. Dr. Simoncini previously taught attending physicians at Temple University how to prescribe PrEP and has done many grand rounds for primary care providers on how to manage PrEP.

“My biggest issue with this data is: What about the people who aren’t going to sexual health clinics?” she said. “What about the kid who’s 16 and maybe just barely putting his feet into the waters of sex and doesn’t feel quite comfortable going to a sexual health clinic? What about the trans Indian girl who can’t get to sexual health clinics because of family stigma and cultural stigma? The more we move toward primary care, the more people need to get on board with this.”

Dr. Sullivan reports no relevant financial relationships. Dr. Simoncini is an employee of AIDS Healthcare Foundation and has received advisory board fees from ViiV Healthcare. Dr. Urbina sits on the scientific advisory councils for Gilead Sciences, ViiV Healthcare, and Merck.

A version of this article first appeared on Medscape.com.

Nearly one in three gay and bisexual men who were diagnosed with HIV at U.K. sexual health clinics didn’t meet the criteria for “high risk” that would signal to a clinician that they would be good candidates for pre-exposure prophylaxis (PrEP).

And that means that people who appear lower risk may still be good candidates for the HIV prevention pills, said Ann Sullivan, MD, consulting physician at Chelsea and Westminster Hospital, London.

“If people are coming forward for PrEP, they have self-identified that they need PrEP, [and] we should be allowing them to take PrEP,” said Dr. Sullivan at the 18th European AIDS Society Conference (EACS 2021). “We just need to trust patients. People know their risk, and we just have to accept that they know what they need best.”

And while this trial was made up of 95% gay and bisexual men, that ethos applies to every other group that could benefit from PrEP, including cisgender and transgender women and other gender-diverse people, Latinos, and Black Americans. In the United States, these groups make up nearly half of those who could benefit from PrEP under older guidelines but account for just 8% of people currently taking PrEP.

The finding also reinforces growing calls from health care providers to reduce gatekeeping around PrEP. For instance, there’s a move underway by the U.S. Centers for Disease Control and Prevention, where drafts of updated PrEP guidelines call for clinicians to talk to any sexually active teenager and adult about PrEP.

For the PrEP Impact trial, gay and bisexual men who received sexual health care at UK National Health Service sexual health clinics were invited to enroll in the study based on national PrEP guidelines. Those guidelines included being a cisgender man who had had sex with men not currently living with HIV and reporting condomless anal sex in the last 3 months; having a male partner whose HIV status they don’t know or who doesn’t have an undetectable viral load and with whom they’ve had condomless anal sex; or someone who doesn’t reach those criteria but whom the clinician thinks would be a good candidate.

Between Oct. 2017 and Feb. 2020, a total of 17,770 gay and bisexual men and 503 transgender or nonbinary people enrolled in the trial and were paired with 97,098 gay and bisexual men who didn’t use PrEP. (Data from the transgender participants were reported in a separate presentation.) The median age was 27 years, with 14.4% of the cisgender gay men between the ages of 16 and 24. Three out of four cis men were White, most lived in London, and more than half came from very-low-income neighborhoods.

Participants and controls were assessed for whether they were at particularly high risk for acquiring HIV, such as having used PrEP, having had two or more HIV tests, having had a rectal bacterial sexually transmitted infection (STI), or having had contact with someone with HIV or syphilis.

At the end of Feb. 2020, 24 cisgender men on PrEP had acquired HIV compared with 670 in the control group – an 87% reduction in HIV acquisition. Only one of those 24 cis men had lab-confirmed high adherence to PrEP. However, because the hair samples used to judge drug concentration weren’t long enough, Dr. Sullivan and colleagues were unable to assess whether the person really was fully adherent to treatment for the length of the trial.

But when they looked at the assessed behavior of people who acquired HIV, the two groups diverged. While a full 92% of people using PrEP had had STI diagnoses and other markers of increased risk, that was true for only 71% of people not taking PrEP. That meant, Dr. Sullivan said in an interview, that screening guidelines for PrEP were missing 29% of people with low assessed risk for HIV who nevertheless acquired the virus.

The findings led Antonio Urbina, MD, who both prescribes PrEP and manages Mount Sinai Medical Center’s PrEP program in New York, to the same conclusion that Dr. Sullivan and her team came to: that no screener is going to account for everything, and that there may be things that patients don’t want to tell their clinicians about their risk, either because of their own internalized stigma or their calculation that they aren’t comfortable enough with their providers to be honest.

“It reinforces to me that I need to ask more open-ended questions regarding risk and then just talk more about PrEP,” said Dr. Urbina, professor of medicine at Icahn School of Medicine. “Risk is dynamic and changes. And the great thing about PrEP is that if the risk goes up or down, if you have PrEP on board, you maintain this protection against HIV.”

An accompanying presentation on the transgender and nonbinary participants in the Impact Trial found that just one of 503 PrEP users acquired HIV. But here, too, there were people who could have benefited from PrEP but didn’t take it: Of the 477 trans and nonbinary participants who acted as controls, 97 were eligible by current guidelines but didn’t take PrEP. One in four of those declined the offer to take PrEP; the rest weren’t able to take it because they lived outside the treatment area. That, combined with a significantly lower likelihood that Black trans and nonbinary people took PrEP, indicated that work needs to be done to address the needs of people geographically and ethnically.

The data on gay men also raised the “who’s left out” issue for Gina Simoncini, MD, medical director for the Philadelphia AIDS Healthcare Foundation Healthcare Center. Dr. Simoncini previously taught attending physicians at Temple University how to prescribe PrEP and has done many grand rounds for primary care providers on how to manage PrEP.

“My biggest issue with this data is: What about the people who aren’t going to sexual health clinics?” she said. “What about the kid who’s 16 and maybe just barely putting his feet into the waters of sex and doesn’t feel quite comfortable going to a sexual health clinic? What about the trans Indian girl who can’t get to sexual health clinics because of family stigma and cultural stigma? The more we move toward primary care, the more people need to get on board with this.”

Dr. Sullivan reports no relevant financial relationships. Dr. Simoncini is an employee of AIDS Healthcare Foundation and has received advisory board fees from ViiV Healthcare. Dr. Urbina sits on the scientific advisory councils for Gilead Sciences, ViiV Healthcare, and Merck.

A version of this article first appeared on Medscape.com.

One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the division of infectious diseases at the University of Ottawa, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”

These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.

“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Dr. Orkin, commenting during the discussion session of the European AIDS Clinical Society 2021 annual meeting. “We’re having to change our model, and it’s challenging.”

In the United States, the Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Dr. Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be noninferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M – which tested the every-other-month approach – and FLAIR trials.

Dr. Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.

Of the 21 people Dr. Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)

Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/mcL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Dr. Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.

Twenty patients switched from integrase-inhibitor regimens, and one had been receiving a nonnucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.

And although the drug has not been approved for shot initiation this way, two patients requested – and Dr. Angel agreed – to start them on the shots without first doing a month of daily pills to check for safety.

“This is my conclusion from these data: the oral lead-in period is not necessary,” Dr. Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”

That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.

At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Dr. Angel called “injection fatigue.”

“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.

Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Dr. Angel said may reduce the odds of injection fatigue.

Dr. Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht (the Netherlands), asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.

“These are not hypothetical conversations,” Dr. Angel said. “I’m having these conversations with patients now – temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”

For now, he said, the answer is, “We’ll figure it out.”

Meanwhile, there’s another big question when it comes to injectables, said Marta Vas ylyev, MD, from Lviv (Ukraine) Regional AIDS Center: When will they be available to the people who might benefit most from them – people in resource-limited settings, people who so far have struggled to remember to take their pills every day?

For now, Dr. Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.

“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or health care staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”

Dr. Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Dr. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Dr. Vasylyev reported no relevant financial relationships.  

A version of this article first appeared on Medscape.com.

One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the division of infectious diseases at the University of Ottawa, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”

These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.

“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Dr. Orkin, commenting during the discussion session of the European AIDS Clinical Society 2021 annual meeting. “We’re having to change our model, and it’s challenging.”

In the United States, the Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Dr. Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be noninferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M – which tested the every-other-month approach – and FLAIR trials.

Dr. Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.

Of the 21 people Dr. Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)

Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/mcL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Dr. Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.

Twenty patients switched from integrase-inhibitor regimens, and one had been receiving a nonnucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.

And although the drug has not been approved for shot initiation this way, two patients requested – and Dr. Angel agreed – to start them on the shots without first doing a month of daily pills to check for safety.

“This is my conclusion from these data: the oral lead-in period is not necessary,” Dr. Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”

That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.

At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Dr. Angel called “injection fatigue.”

“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.

Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Dr. Angel said may reduce the odds of injection fatigue.

Dr. Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht (the Netherlands), asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.

“These are not hypothetical conversations,” Dr. Angel said. “I’m having these conversations with patients now – temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”

For now, he said, the answer is, “We’ll figure it out.”

Meanwhile, there’s another big question when it comes to injectables, said Marta Vas ylyev, MD, from Lviv (Ukraine) Regional AIDS Center: When will they be available to the people who might benefit most from them – people in resource-limited settings, people who so far have struggled to remember to take their pills every day?

For now, Dr. Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.

“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or health care staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”

Dr. Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Dr. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Dr. Vasylyev reported no relevant financial relationships.  

A version of this article first appeared on Medscape.com.

One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the division of infectious diseases at the University of Ottawa, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”

These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.

“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Dr. Orkin, commenting during the discussion session of the European AIDS Clinical Society 2021 annual meeting. “We’re having to change our model, and it’s challenging.”

In the United States, the Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Dr. Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be noninferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M – which tested the every-other-month approach – and FLAIR trials.

Dr. Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.

Of the 21 people Dr. Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)

Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/mcL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Dr. Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.

Twenty patients switched from integrase-inhibitor regimens, and one had been receiving a nonnucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.

And although the drug has not been approved for shot initiation this way, two patients requested – and Dr. Angel agreed – to start them on the shots without first doing a month of daily pills to check for safety.

“This is my conclusion from these data: the oral lead-in period is not necessary,” Dr. Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”

That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.

At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Dr. Angel called “injection fatigue.”

“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.

Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Dr. Angel said may reduce the odds of injection fatigue.

Dr. Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht (the Netherlands), asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.

“These are not hypothetical conversations,” Dr. Angel said. “I’m having these conversations with patients now – temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”

For now, he said, the answer is, “We’ll figure it out.”

Meanwhile, there’s another big question when it comes to injectables, said Marta Vas ylyev, MD, from Lviv (Ukraine) Regional AIDS Center: When will they be available to the people who might benefit most from them – people in resource-limited settings, people who so far have struggled to remember to take their pills every day?

For now, Dr. Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.

“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or health care staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”

Dr. Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Dr. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Dr. Vasylyev reported no relevant financial relationships.  

A version of this article first appeared on Medscape.com.

George Froehle, PA, a primary care clinician at CentraCare in rural St. Cloud, Minn., has been prescribing the HIV prevention pill tenofovir disoproxil fumarate plus emtricitabine since it was marketed by the brand name Truvada and the Food and Drug Administration approved it in 2012. But recently, he’s been having conversations with patients about the new HIV prevention pill, tenofovir alafenamide plus emtricitabine (TAF/FTC, Descovy) as well.

“They may have a friend who has heard that Descovy is newer and safer,” Mr. Froehle said. But that’s not necessarily the case, at least according to lab values. A recent study in the journal Open Forum Infectious Diseases suggests that only between 1 in 10 and 1 in 3 switches to the new formulation of HIV pre-exposure prophylaxis (PrEP) are indicated by lab work – and that nearly half of people receiving a prescription for the new version had lab results actually contraindicating the switch.

This, combined with the lower cost of generic Truvada and the steep cost of Descovy, led study coauthor and HIV PrEP prescriber Douglas Krakower, MD, and colleagues to suggest that the generic version should be standard of care for all people on PrEP unless otherwise indicated.

This just “makes good sense,” Dr. Krakower, assistant professor of medicine at Harvard Medical School, Boston, told this news organization.

“It’s important to ultimately allow for patients and providers to have access to all of the PrEP options so they can choose the best option for each person,” he said. “But our data suggest that strategies to optimize the cost-effectiveness of PrEP prescribing, such as formulary interventions and education for patients and providers, could be beneficial – as long as there is an easy mechanism for patients and providers to override restrictions when there are clinical indications.”

Current PrEP guidelines from the Centers for Disease Control and Prevention don’t list a first-line or second-line treatment for PrEP. But recent guidance issued to insurance companies by the Biden administration specifically grants insurers permission to employ stepped formularies and cost sharing.

“Since the branded version of PrEP is not specified in the [U.S. Preventive Services Task Force] recommendation, plans and issuers may cover a generic version of PrEP without cost sharing and impose cost sharing on an equivalent branded version,” the rule, issued July 19, states. “However, plans and insurers must accommodate any individual for whom a particular PrEP medication [generic or brand name] would be medically inappropriate, as determined by the individual’s health care provider, by having a mechanism for waiving the otherwise applicable cost-sharing for the brand or nonpreferred brand version.”

Both drugs have been found to be 99% effective in stopping HIV acquisition in people at risk for it. Descovy is approved specifically for gay and bisexual men, transgender women, and anyone having anal sex. Ongoing studies are looking at the effectiveness of Descovy in people having vaginal sex. Generic Truvada has been approved for all people.
 

The biomarkers of switching

To be clear, both medicines are exceedingly safe, said lead author and epidemiologist Julia Marcus, PhD, MPH, associate professor at Harvard Medical School. Side effects have been mild and include nausea and diarrhea in the first month. What lab work tells clinicians is the potential for physiologic changes, but those changes don’t necessarily translate to clinical events.

“When I say harmful, I mean potentially harmful,” she said in an interview. “It’s really based on these incremental changes that maybe, in the long run, could be harmful.”

But she added that there are two types of damage from medicines: “There’s potential physiological damage, but there’s also potential financial damage.” While generic Truvada has a list price as low as $30 a bottle, Descovy has a list price of up to $2,000 a month. And the push for PrEP is growing. Recently, the head of the division of HIV/AIDS at the National Institute of Allergy and Infectious Diseases urged providers to get all their “HIV-negative, at-risk patients on PrEP tomorrow,” in light of the latest HIV vaccine failure.

So Dr. Marcus and team looked at data from the 2892 people who started taking PrEP in the year before the FDA approved Descovy in October 2019. Participants accessed PrEP through Fenway Health, a Boston-area health clinic serving a largely gay, lesbian, bisexual, transgender, and otherwise queer population, and the largest PrEP prescriber in New England. They then tracked which participants switched to Descovy and correlated the switches to lab work and CDC guidance for PrEP.

What they found was that just 11.9% of participants, or 343 people, switched to the newer formulation. That’s lower than the 27.2% who switched in nationally available data, which were released at a recent HIV conference. But when Dr. Krakower and colleagues looked at whether their PrEP prescriptions were appropriate based on the patients’ lab work, the findings were mixed.

On the one hand, they showed that 24 of those 343 people who switched to Descovy had creatinine clearance levels or bone mineral density measurements low enough to make the switch a good option. But that’s just 7% of all people who switched. They then ran a secondary model, in which they broadened the criteria for a switch from strictly those lab values to conditions that might indicate borderline kidney function, which could eventually lead to kidney damage. These included diagnoses of hypertension or diabetes, or borderline creatinine levels between 60 and 70 mL/minute.

“Even when we defined clinical indications as generously as we could, we still saw that only a minority had clinical indications for switching,” said “Most of the switching to TAF/FTC was potentially unnecessary, and some of it may have been harmful for people who had cardiovascular risk factors.”

That’s because although Descovy doesn’t affect renal and bone mineral markers, it does affect cholesterol levels and weight. Aftermarket and FDA data revealed a small but noticeable increase in statin use among people taking the new brand-name PrEP pill. When Marcus and colleagues looked for those biomarkers – total cholesterol greater than200, BMI of 30 or more, LDL cholesterol of more than 160 or HDL cholesterol of less than 40 – 14% of switches fit the criteria for contraindications for Descovy. That’s 10 times the rate of potential harm in switching as there was for those who stayed on the generic Truvada and would have been better served on Descovy. That came in at just 1.4%.

“There may be many reasons why patients or providers might choose to switch that we couldn’t document in our study,” she said. For instance, the newer formulation, Descovy, is a significantly smaller pill than the generic is. Or the perception of novelty might drive some switches.

“But I think we need qualitative work to understand how these decisions are being made,” she said in an interview. “It will be important to follow these patients to see what happens in terms of clinical outcomes.”

For his part, Mr. Froehle found the study intriguing. It reflects his own thinking around the value of the newer formulation. He also prescribes for people living with HIV. For them, the benefit of the new formulation of tenofovir present in Descovy has clear clinical relevance. After all, people living with HIV can be on their drug regimens for decades.

But people on PrEP aren’t likely to be on the pills as long, and so the real benefit of the newer, more expensive formulation is less clear. And he added that he’s already getting “pushback” from some insurance companies on the name-brand version, with companies asking for proof via lab values that a person has a history of kidney impairment or bone mineral density loss.

“It doesn’t happen a ton,” he said. “But it’s starting to happen, and normally it kind of builds from there.”

So when a patient comes in and asks specifically for Descovy, he usually will talk to them about it.

“If it’s what the patient wants and insurance covers it and it’s not unsafe for them to be on it, there might not be a reason to not prescribe Descovy,” said Mr. Froehle, who served as a sub-principal investigator for the DISCOVER clinical trial that showed the new PrEP was as effective as Truvada. “But now with Truvada being generic, we will talk about Truvada as being something we start up front because it may have a lower cost and it’s cheaper to the system. Then we can always switch to Descovy as needed.”

This study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Marcus reported receiving fees from Kaiser Permanente Northern California on a research grant from Gilead Sciences. Dr. Krakower reported having conducted research that was funded by Gilead Sciences and Merck, as well as honoraria for medical education content and presentations for Medscape Medical News, MED-IQ, and DKBMed and royalties from work conducted by UpToDate. Mr. Froehle reported receiving fees from Gilead Sciences in connection with a Gilead advisory board.

A version of this article first appeared on Medscape.com.

George Froehle, PA, a primary care clinician at CentraCare in rural St. Cloud, Minn., has been prescribing the HIV prevention pill tenofovir disoproxil fumarate plus emtricitabine since it was marketed by the brand name Truvada and the Food and Drug Administration approved it in 2012. But recently, he’s been having conversations with patients about the new HIV prevention pill, tenofovir alafenamide plus emtricitabine (TAF/FTC, Descovy) as well.

“They may have a friend who has heard that Descovy is newer and safer,” Mr. Froehle said. But that’s not necessarily the case, at least according to lab values. A recent study in the journal Open Forum Infectious Diseases suggests that only between 1 in 10 and 1 in 3 switches to the new formulation of HIV pre-exposure prophylaxis (PrEP) are indicated by lab work – and that nearly half of people receiving a prescription for the new version had lab results actually contraindicating the switch.

This, combined with the lower cost of generic Truvada and the steep cost of Descovy, led study coauthor and HIV PrEP prescriber Douglas Krakower, MD, and colleagues to suggest that the generic version should be standard of care for all people on PrEP unless otherwise indicated.

This just “makes good sense,” Dr. Krakower, assistant professor of medicine at Harvard Medical School, Boston, told this news organization.

“It’s important to ultimately allow for patients and providers to have access to all of the PrEP options so they can choose the best option for each person,” he said. “But our data suggest that strategies to optimize the cost-effectiveness of PrEP prescribing, such as formulary interventions and education for patients and providers, could be beneficial – as long as there is an easy mechanism for patients and providers to override restrictions when there are clinical indications.”

Current PrEP guidelines from the Centers for Disease Control and Prevention don’t list a first-line or second-line treatment for PrEP. But recent guidance issued to insurance companies by the Biden administration specifically grants insurers permission to employ stepped formularies and cost sharing.

“Since the branded version of PrEP is not specified in the [U.S. Preventive Services Task Force] recommendation, plans and issuers may cover a generic version of PrEP without cost sharing and impose cost sharing on an equivalent branded version,” the rule, issued July 19, states. “However, plans and insurers must accommodate any individual for whom a particular PrEP medication [generic or brand name] would be medically inappropriate, as determined by the individual’s health care provider, by having a mechanism for waiving the otherwise applicable cost-sharing for the brand or nonpreferred brand version.”

Both drugs have been found to be 99% effective in stopping HIV acquisition in people at risk for it. Descovy is approved specifically for gay and bisexual men, transgender women, and anyone having anal sex. Ongoing studies are looking at the effectiveness of Descovy in people having vaginal sex. Generic Truvada has been approved for all people.
 

The biomarkers of switching

To be clear, both medicines are exceedingly safe, said lead author and epidemiologist Julia Marcus, PhD, MPH, associate professor at Harvard Medical School. Side effects have been mild and include nausea and diarrhea in the first month. What lab work tells clinicians is the potential for physiologic changes, but those changes don’t necessarily translate to clinical events.

“When I say harmful, I mean potentially harmful,” she said in an interview. “It’s really based on these incremental changes that maybe, in the long run, could be harmful.”

But she added that there are two types of damage from medicines: “There’s potential physiological damage, but there’s also potential financial damage.” While generic Truvada has a list price as low as $30 a bottle, Descovy has a list price of up to $2,000 a month. And the push for PrEP is growing. Recently, the head of the division of HIV/AIDS at the National Institute of Allergy and Infectious Diseases urged providers to get all their “HIV-negative, at-risk patients on PrEP tomorrow,” in light of the latest HIV vaccine failure.

So Dr. Marcus and team looked at data from the 2892 people who started taking PrEP in the year before the FDA approved Descovy in October 2019. Participants accessed PrEP through Fenway Health, a Boston-area health clinic serving a largely gay, lesbian, bisexual, transgender, and otherwise queer population, and the largest PrEP prescriber in New England. They then tracked which participants switched to Descovy and correlated the switches to lab work and CDC guidance for PrEP.

What they found was that just 11.9% of participants, or 343 people, switched to the newer formulation. That’s lower than the 27.2% who switched in nationally available data, which were released at a recent HIV conference. But when Dr. Krakower and colleagues looked at whether their PrEP prescriptions were appropriate based on the patients’ lab work, the findings were mixed.

On the one hand, they showed that 24 of those 343 people who switched to Descovy had creatinine clearance levels or bone mineral density measurements low enough to make the switch a good option. But that’s just 7% of all people who switched. They then ran a secondary model, in which they broadened the criteria for a switch from strictly those lab values to conditions that might indicate borderline kidney function, which could eventually lead to kidney damage. These included diagnoses of hypertension or diabetes, or borderline creatinine levels between 60 and 70 mL/minute.

“Even when we defined clinical indications as generously as we could, we still saw that only a minority had clinical indications for switching,” said “Most of the switching to TAF/FTC was potentially unnecessary, and some of it may have been harmful for people who had cardiovascular risk factors.”

That’s because although Descovy doesn’t affect renal and bone mineral markers, it does affect cholesterol levels and weight. Aftermarket and FDA data revealed a small but noticeable increase in statin use among people taking the new brand-name PrEP pill. When Marcus and colleagues looked for those biomarkers – total cholesterol greater than200, BMI of 30 or more, LDL cholesterol of more than 160 or HDL cholesterol of less than 40 – 14% of switches fit the criteria for contraindications for Descovy. That’s 10 times the rate of potential harm in switching as there was for those who stayed on the generic Truvada and would have been better served on Descovy. That came in at just 1.4%.

“There may be many reasons why patients or providers might choose to switch that we couldn’t document in our study,” she said. For instance, the newer formulation, Descovy, is a significantly smaller pill than the generic is. Or the perception of novelty might drive some switches.

“But I think we need qualitative work to understand how these decisions are being made,” she said in an interview. “It will be important to follow these patients to see what happens in terms of clinical outcomes.”

For his part, Mr. Froehle found the study intriguing. It reflects his own thinking around the value of the newer formulation. He also prescribes for people living with HIV. For them, the benefit of the new formulation of tenofovir present in Descovy has clear clinical relevance. After all, people living with HIV can be on their drug regimens for decades.

But people on PrEP aren’t likely to be on the pills as long, and so the real benefit of the newer, more expensive formulation is less clear. And he added that he’s already getting “pushback” from some insurance companies on the name-brand version, with companies asking for proof via lab values that a person has a history of kidney impairment or bone mineral density loss.

“It doesn’t happen a ton,” he said. “But it’s starting to happen, and normally it kind of builds from there.”

So when a patient comes in and asks specifically for Descovy, he usually will talk to them about it.

“If it’s what the patient wants and insurance covers it and it’s not unsafe for them to be on it, there might not be a reason to not prescribe Descovy,” said Mr. Froehle, who served as a sub-principal investigator for the DISCOVER clinical trial that showed the new PrEP was as effective as Truvada. “But now with Truvada being generic, we will talk about Truvada as being something we start up front because it may have a lower cost and it’s cheaper to the system. Then we can always switch to Descovy as needed.”

This study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Marcus reported receiving fees from Kaiser Permanente Northern California on a research grant from Gilead Sciences. Dr. Krakower reported having conducted research that was funded by Gilead Sciences and Merck, as well as honoraria for medical education content and presentations for Medscape Medical News, MED-IQ, and DKBMed and royalties from work conducted by UpToDate. Mr. Froehle reported receiving fees from Gilead Sciences in connection with a Gilead advisory board.

A version of this article first appeared on Medscape.com.

George Froehle, PA, a primary care clinician at CentraCare in rural St. Cloud, Minn., has been prescribing the HIV prevention pill tenofovir disoproxil fumarate plus emtricitabine since it was marketed by the brand name Truvada and the Food and Drug Administration approved it in 2012. But recently, he’s been having conversations with patients about the new HIV prevention pill, tenofovir alafenamide plus emtricitabine (TAF/FTC, Descovy) as well.

“They may have a friend who has heard that Descovy is newer and safer,” Mr. Froehle said. But that’s not necessarily the case, at least according to lab values. A recent study in the journal Open Forum Infectious Diseases suggests that only between 1 in 10 and 1 in 3 switches to the new formulation of HIV pre-exposure prophylaxis (PrEP) are indicated by lab work – and that nearly half of people receiving a prescription for the new version had lab results actually contraindicating the switch.

This, combined with the lower cost of generic Truvada and the steep cost of Descovy, led study coauthor and HIV PrEP prescriber Douglas Krakower, MD, and colleagues to suggest that the generic version should be standard of care for all people on PrEP unless otherwise indicated.

This just “makes good sense,” Dr. Krakower, assistant professor of medicine at Harvard Medical School, Boston, told this news organization.

“It’s important to ultimately allow for patients and providers to have access to all of the PrEP options so they can choose the best option for each person,” he said. “But our data suggest that strategies to optimize the cost-effectiveness of PrEP prescribing, such as formulary interventions and education for patients and providers, could be beneficial – as long as there is an easy mechanism for patients and providers to override restrictions when there are clinical indications.”

Current PrEP guidelines from the Centers for Disease Control and Prevention don’t list a first-line or second-line treatment for PrEP. But recent guidance issued to insurance companies by the Biden administration specifically grants insurers permission to employ stepped formularies and cost sharing.

“Since the branded version of PrEP is not specified in the [U.S. Preventive Services Task Force] recommendation, plans and issuers may cover a generic version of PrEP without cost sharing and impose cost sharing on an equivalent branded version,” the rule, issued July 19, states. “However, plans and insurers must accommodate any individual for whom a particular PrEP medication [generic or brand name] would be medically inappropriate, as determined by the individual’s health care provider, by having a mechanism for waiving the otherwise applicable cost-sharing for the brand or nonpreferred brand version.”

Both drugs have been found to be 99% effective in stopping HIV acquisition in people at risk for it. Descovy is approved specifically for gay and bisexual men, transgender women, and anyone having anal sex. Ongoing studies are looking at the effectiveness of Descovy in people having vaginal sex. Generic Truvada has been approved for all people.
 

The biomarkers of switching

To be clear, both medicines are exceedingly safe, said lead author and epidemiologist Julia Marcus, PhD, MPH, associate professor at Harvard Medical School. Side effects have been mild and include nausea and diarrhea in the first month. What lab work tells clinicians is the potential for physiologic changes, but those changes don’t necessarily translate to clinical events.

“When I say harmful, I mean potentially harmful,” she said in an interview. “It’s really based on these incremental changes that maybe, in the long run, could be harmful.”

But she added that there are two types of damage from medicines: “There’s potential physiological damage, but there’s also potential financial damage.” While generic Truvada has a list price as low as $30 a bottle, Descovy has a list price of up to $2,000 a month. And the push for PrEP is growing. Recently, the head of the division of HIV/AIDS at the National Institute of Allergy and Infectious Diseases urged providers to get all their “HIV-negative, at-risk patients on PrEP tomorrow,” in light of the latest HIV vaccine failure.

So Dr. Marcus and team looked at data from the 2892 people who started taking PrEP in the year before the FDA approved Descovy in October 2019. Participants accessed PrEP through Fenway Health, a Boston-area health clinic serving a largely gay, lesbian, bisexual, transgender, and otherwise queer population, and the largest PrEP prescriber in New England. They then tracked which participants switched to Descovy and correlated the switches to lab work and CDC guidance for PrEP.

What they found was that just 11.9% of participants, or 343 people, switched to the newer formulation. That’s lower than the 27.2% who switched in nationally available data, which were released at a recent HIV conference. But when Dr. Krakower and colleagues looked at whether their PrEP prescriptions were appropriate based on the patients’ lab work, the findings were mixed.

On the one hand, they showed that 24 of those 343 people who switched to Descovy had creatinine clearance levels or bone mineral density measurements low enough to make the switch a good option. But that’s just 7% of all people who switched. They then ran a secondary model, in which they broadened the criteria for a switch from strictly those lab values to conditions that might indicate borderline kidney function, which could eventually lead to kidney damage. These included diagnoses of hypertension or diabetes, or borderline creatinine levels between 60 and 70 mL/minute.

“Even when we defined clinical indications as generously as we could, we still saw that only a minority had clinical indications for switching,” said “Most of the switching to TAF/FTC was potentially unnecessary, and some of it may have been harmful for people who had cardiovascular risk factors.”

That’s because although Descovy doesn’t affect renal and bone mineral markers, it does affect cholesterol levels and weight. Aftermarket and FDA data revealed a small but noticeable increase in statin use among people taking the new brand-name PrEP pill. When Marcus and colleagues looked for those biomarkers – total cholesterol greater than200, BMI of 30 or more, LDL cholesterol of more than 160 or HDL cholesterol of less than 40 – 14% of switches fit the criteria for contraindications for Descovy. That’s 10 times the rate of potential harm in switching as there was for those who stayed on the generic Truvada and would have been better served on Descovy. That came in at just 1.4%.

“There may be many reasons why patients or providers might choose to switch that we couldn’t document in our study,” she said. For instance, the newer formulation, Descovy, is a significantly smaller pill than the generic is. Or the perception of novelty might drive some switches.

“But I think we need qualitative work to understand how these decisions are being made,” she said in an interview. “It will be important to follow these patients to see what happens in terms of clinical outcomes.”

For his part, Mr. Froehle found the study intriguing. It reflects his own thinking around the value of the newer formulation. He also prescribes for people living with HIV. For them, the benefit of the new formulation of tenofovir present in Descovy has clear clinical relevance. After all, people living with HIV can be on their drug regimens for decades.

But people on PrEP aren’t likely to be on the pills as long, and so the real benefit of the newer, more expensive formulation is less clear. And he added that he’s already getting “pushback” from some insurance companies on the name-brand version, with companies asking for proof via lab values that a person has a history of kidney impairment or bone mineral density loss.

“It doesn’t happen a ton,” he said. “But it’s starting to happen, and normally it kind of builds from there.”

So when a patient comes in and asks specifically for Descovy, he usually will talk to them about it.

“If it’s what the patient wants and insurance covers it and it’s not unsafe for them to be on it, there might not be a reason to not prescribe Descovy,” said Mr. Froehle, who served as a sub-principal investigator for the DISCOVER clinical trial that showed the new PrEP was as effective as Truvada. “But now with Truvada being generic, we will talk about Truvada as being something we start up front because it may have a lower cost and it’s cheaper to the system. Then we can always switch to Descovy as needed.”

This study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Marcus reported receiving fees from Kaiser Permanente Northern California on a research grant from Gilead Sciences. Dr. Krakower reported having conducted research that was funded by Gilead Sciences and Merck, as well as honoraria for medical education content and presentations for Medscape Medical News, MED-IQ, and DKBMed and royalties from work conducted by UpToDate. Mr. Froehle reported receiving fees from Gilead Sciences in connection with a Gilead advisory board.

A version of this article first appeared on Medscape.com.

Last year, Katherine Gill, MBChB, an HIV prevention researcher in Cape Town, South Africa, realized how jaded she’d become to vaccine research when the Pfizer COVID-19 vaccine came back as 95% effective. In her career conducting HIV clinical trials, she had never seen anything like it. Even HIV prevention methods she had studied that had worked, such as the dapivirine ring, had an overall efficacy of 30%.

The COVID-19 success story started to soften her views toward another vaccine trial she was helping to conduct, a trial in HIV that used the same platform as Johnson & Johnson’s successful COVID-19 vaccine.

“When the COVID vaccine was cracked so quickly and seemingly quite easily, I did start to think, ‘Well, maybe … maybe this will work for HIV,’ “ she said in an interview.

That turned out to be false hope. The National Institutes of Health (NIH) announced that the trial Dr. Gill was helping to conduct, HVTN 705, was stopping early because it hadn’t generated enough of an immune response in participants to justify continuing. It was the second HIV vaccine to fail in the last year. It’s also the latest in what has been a litany of disappointments in the attempt to boost the human immune system to fight HIV without the need for ongoing HIV treatment.

In HVTN 705, known as the Imbokodo study (imbokodo is a Zulu word that’s part of a saying about women being strong as rocks), researchers used the platform made up of a common cold virus, adenovirus 26, to deliver a computer-generated mosaic of HIV antigens to participants’ immune systems. That mosaic of antigens is meant to goose the immune system into recognizing HIV if it were exposed to it.

When HIV enters the body, it infiltrates immune cells and replicates within them. To the rest of the immune system, those cells still register as just typical T-cells. The rest of the immune system can’t see that the virus is spreading through the very cells meant to protect the body from illness. That, plus the armor of sugary glycoproteins encasing the virus, has made HIV nearly impervious to vaccination.

Then, those so-called “prime” shots were followed by a second shot that targets glycoprotein 140, on the most common HIV subtype (or clade) in Africa, clade C. In the Imbokodo trial, a total of 2,637 women from five sub-Saharan African countries received shots at baseline, 3 months, 6 months, and 1 year. Then researchers followed the women from month 7 to 2 years after their third dose, testing their blood to see if their immune systems had generated the immune response the vaccine was meant to induce – and whether such immune response was associated with lower rates of HIV.

When researchers looked at the first 2 years of data, they learned that the vaccine was safe. And they found a total of 114 new cases of HIV – 51 among women who received the vaccine and 63 among those who received a placebo. That’s a 25.2% efficacy rate – but it wasn’t statistically significant.

The results are frustrating, said Carl Dieffenbach, PhD, director of the AIDS division at the National Institute of Allergy and Infectious Diseases (NIAID). NIAID is one of the funders of the study.

“This [trial] is a little more confounding, in that there is this low level of statistically insignificant difference between vaccine and placebo that starts somewhere around month 9 and then just kind of indolently is maintained over the next 15 months,” he said in an interview. “That’s kind of frustrating. Does it mean there’s a signal or is this just chance? Because that’s what statistics tell us, not to believe your last data point.”

What this means for the future direction of vaccine research is unclear. A sister study to Imbokodo, called Mosaico, recently finished enrolling participants. Mosaico uses the same adenovirus 26 platform, but it’s loaded with different antigens and targets a different glycoprotein for a different HIV subtype. If that trial shows success, it could mean that the platform is right, but the targets in the Imbokodo vaccine were wrong.

Dr. Dieffenbach said that before NIAID decides what to do with Mosaico they’ve asked researchers to analyze the data on the people who did respond, to see if those people have some specific variant of HIV or some other biomarker that could be used to form the next iteration of an HIV vaccine candidate. Only after that will they make a decision about Mosaico.

But he added that it does make him wonder if vaccine approaches that rely on nonneutralizing antibodies like this one have a ceiling of effectiveness that’s just too low to alter the course of the epidemic.

“I think we’ve discovered that there’s not a floor to [these nonneutralizing approaches], but there probably is a ceiling,” he said. “I don’t know if we’re going to get better than” a 25%-29% efficacy rate with those approaches.

The Imbokodo findings reminded Mitchell Warren, executive director of the global HIV prevention nonprofit, AVAC, of the data released in January from the Antibody Mediated Prevention (AMP) trial. That trial pitted the broadly neutralizing antibody (bNAb) VCR01 against HIV – and mostly, it lost.

VCR01 worked only on HIV variants that 30% of participants had. But in those 30%, it was 75% effective at preventing HIV. Now you have Imbokodo, with its potential 25% activity against HIV, something that may have been a fluke. This, to Mr. Warren, requires a rethinking of the whole HIV vaccine enterprise while “doubling, tripling, quadrupling down” on the HIV prevention methods we know work, such as preexposure prophylaxis (PrEP).

Dr. Dieffenbach agreed. To clinicians, Dr. Dieffenbach said the message of this HIV vaccine trial is flush with urgency: “Get your HIV-negative, at-risk people on PrEP tomorrow.”

There are now two pills approved for HIV prevention, both of which have been found to be up to 99% effective when taken consistently. A third option, injectable cabotegravir (Vocabria), has been submitted to the Food and Drug Administration for approval. The federal Ready, Set, PrEP program makes the pill available for free for those who qualify, and recently the Biden administration reaffirmed that, under the Affordable Care Act, insurance companies should cover all costs associated with PrEP, including lab work and exam visits.

But for the 157 women who participated in the trial at Dr. Gill’s site in Masiphumelele, on the southwestern tip of South Africa, the trial was personal, said Jason Naidoo, community liaison officer at the Desmond Tutu HIV Foundation, which conducted a portion of the study. These were women whose parents, siblings, or children were living with HIV or had died from AIDS-defining illnesses, he said. Their lives were chaotic, traveling at a moment’s notice to hometowns on the Eastern Cape, an 11-hour car ride away – longer by bus – for traditional prayers, funerals, and other important events.

Mr. Naidoo remembers arranging buses for the women to return for scheduled clinic visits, leaving the Eastern Cape in the afternoon and arriving in Masiphumelele in the early morning hours, just to keep the clinic appointment. Then, they’d turn around and return east.

They did this for 3 years, he said.

“The fact that these participants have stuck to this and been dedicated amidst all of the chaos talks about their commitment to actually having a vaccine for HIV,” he said. “They know their own risk profile as young Black women in South Africa, and they understand the need for an intervention for the future generations.

“So you can understand the emotion and the sense of sadness, the disappointment – the incredible [dis]belief that this [the failure of the vaccine] could have happened, because the expectations are so, so high.”

For Dr. Gill, who is lead investigator for Imbokodo in Masiphumelele, the weariness toward vaccines is back. Another trial is underway for an HIV vaccine with a platform that was successful in COVID-19 – using messenger RNA (mRNA), like the Pfizer and Moderna COVID-19 vaccines did.

“I think we need to be careful,” she said, “thinking that the mRNA vaccines are going to crack it.”

Dr. Dieffenbach, Dr. Gill, and Mr. Naidoo have disclosed no relevant financial relationships. The study was funded by Janssen, a Johnson & Johnson company, with NIAID and the Bill and Melinda Gates Foundation.

A version of this article first appeared on Medscape.com.

Last year, Katherine Gill, MBChB, an HIV prevention researcher in Cape Town, South Africa, realized how jaded she’d become to vaccine research when the Pfizer COVID-19 vaccine came back as 95% effective. In her career conducting HIV clinical trials, she had never seen anything like it. Even HIV prevention methods she had studied that had worked, such as the dapivirine ring, had an overall efficacy of 30%.

The COVID-19 success story started to soften her views toward another vaccine trial she was helping to conduct, a trial in HIV that used the same platform as Johnson & Johnson’s successful COVID-19 vaccine.

“When the COVID vaccine was cracked so quickly and seemingly quite easily, I did start to think, ‘Well, maybe … maybe this will work for HIV,’ “ she said in an interview.

That turned out to be false hope. The National Institutes of Health (NIH) announced that the trial Dr. Gill was helping to conduct, HVTN 705, was stopping early because it hadn’t generated enough of an immune response in participants to justify continuing. It was the second HIV vaccine to fail in the last year. It’s also the latest in what has been a litany of disappointments in the attempt to boost the human immune system to fight HIV without the need for ongoing HIV treatment.

In HVTN 705, known as the Imbokodo study (imbokodo is a Zulu word that’s part of a saying about women being strong as rocks), researchers used the platform made up of a common cold virus, adenovirus 26, to deliver a computer-generated mosaic of HIV antigens to participants’ immune systems. That mosaic of antigens is meant to goose the immune system into recognizing HIV if it were exposed to it.

When HIV enters the body, it infiltrates immune cells and replicates within them. To the rest of the immune system, those cells still register as just typical T-cells. The rest of the immune system can’t see that the virus is spreading through the very cells meant to protect the body from illness. That, plus the armor of sugary glycoproteins encasing the virus, has made HIV nearly impervious to vaccination.

Then, those so-called “prime” shots were followed by a second shot that targets glycoprotein 140, on the most common HIV subtype (or clade) in Africa, clade C. In the Imbokodo trial, a total of 2,637 women from five sub-Saharan African countries received shots at baseline, 3 months, 6 months, and 1 year. Then researchers followed the women from month 7 to 2 years after their third dose, testing their blood to see if their immune systems had generated the immune response the vaccine was meant to induce – and whether such immune response was associated with lower rates of HIV.

When researchers looked at the first 2 years of data, they learned that the vaccine was safe. And they found a total of 114 new cases of HIV – 51 among women who received the vaccine and 63 among those who received a placebo. That’s a 25.2% efficacy rate – but it wasn’t statistically significant.

The results are frustrating, said Carl Dieffenbach, PhD, director of the AIDS division at the National Institute of Allergy and Infectious Diseases (NIAID). NIAID is one of the funders of the study.

“This [trial] is a little more confounding, in that there is this low level of statistically insignificant difference between vaccine and placebo that starts somewhere around month 9 and then just kind of indolently is maintained over the next 15 months,” he said in an interview. “That’s kind of frustrating. Does it mean there’s a signal or is this just chance? Because that’s what statistics tell us, not to believe your last data point.”

What this means for the future direction of vaccine research is unclear. A sister study to Imbokodo, called Mosaico, recently finished enrolling participants. Mosaico uses the same adenovirus 26 platform, but it’s loaded with different antigens and targets a different glycoprotein for a different HIV subtype. If that trial shows success, it could mean that the platform is right, but the targets in the Imbokodo vaccine were wrong.

Dr. Dieffenbach said that before NIAID decides what to do with Mosaico they’ve asked researchers to analyze the data on the people who did respond, to see if those people have some specific variant of HIV or some other biomarker that could be used to form the next iteration of an HIV vaccine candidate. Only after that will they make a decision about Mosaico.

But he added that it does make him wonder if vaccine approaches that rely on nonneutralizing antibodies like this one have a ceiling of effectiveness that’s just too low to alter the course of the epidemic.

“I think we’ve discovered that there’s not a floor to [these nonneutralizing approaches], but there probably is a ceiling,” he said. “I don’t know if we’re going to get better than” a 25%-29% efficacy rate with those approaches.

The Imbokodo findings reminded Mitchell Warren, executive director of the global HIV prevention nonprofit, AVAC, of the data released in January from the Antibody Mediated Prevention (AMP) trial. That trial pitted the broadly neutralizing antibody (bNAb) VCR01 against HIV – and mostly, it lost.

VCR01 worked only on HIV variants that 30% of participants had. But in those 30%, it was 75% effective at preventing HIV. Now you have Imbokodo, with its potential 25% activity against HIV, something that may have been a fluke. This, to Mr. Warren, requires a rethinking of the whole HIV vaccine enterprise while “doubling, tripling, quadrupling down” on the HIV prevention methods we know work, such as preexposure prophylaxis (PrEP).

Dr. Dieffenbach agreed. To clinicians, Dr. Dieffenbach said the message of this HIV vaccine trial is flush with urgency: “Get your HIV-negative, at-risk people on PrEP tomorrow.”

There are now two pills approved for HIV prevention, both of which have been found to be up to 99% effective when taken consistently. A third option, injectable cabotegravir (Vocabria), has been submitted to the Food and Drug Administration for approval. The federal Ready, Set, PrEP program makes the pill available for free for those who qualify, and recently the Biden administration reaffirmed that, under the Affordable Care Act, insurance companies should cover all costs associated with PrEP, including lab work and exam visits.

But for the 157 women who participated in the trial at Dr. Gill’s site in Masiphumelele, on the southwestern tip of South Africa, the trial was personal, said Jason Naidoo, community liaison officer at the Desmond Tutu HIV Foundation, which conducted a portion of the study. These were women whose parents, siblings, or children were living with HIV or had died from AIDS-defining illnesses, he said. Their lives were chaotic, traveling at a moment’s notice to hometowns on the Eastern Cape, an 11-hour car ride away – longer by bus – for traditional prayers, funerals, and other important events.

Mr. Naidoo remembers arranging buses for the women to return for scheduled clinic visits, leaving the Eastern Cape in the afternoon and arriving in Masiphumelele in the early morning hours, just to keep the clinic appointment. Then, they’d turn around and return east.

They did this for 3 years, he said.

“The fact that these participants have stuck to this and been dedicated amidst all of the chaos talks about their commitment to actually having a vaccine for HIV,” he said. “They know their own risk profile as young Black women in South Africa, and they understand the need for an intervention for the future generations.

“So you can understand the emotion and the sense of sadness, the disappointment – the incredible [dis]belief that this [the failure of the vaccine] could have happened, because the expectations are so, so high.”

For Dr. Gill, who is lead investigator for Imbokodo in Masiphumelele, the weariness toward vaccines is back. Another trial is underway for an HIV vaccine with a platform that was successful in COVID-19 – using messenger RNA (mRNA), like the Pfizer and Moderna COVID-19 vaccines did.

“I think we need to be careful,” she said, “thinking that the mRNA vaccines are going to crack it.”

Dr. Dieffenbach, Dr. Gill, and Mr. Naidoo have disclosed no relevant financial relationships. The study was funded by Janssen, a Johnson & Johnson company, with NIAID and the Bill and Melinda Gates Foundation.

A version of this article first appeared on Medscape.com.

Last year, Katherine Gill, MBChB, an HIV prevention researcher in Cape Town, South Africa, realized how jaded she’d become to vaccine research when the Pfizer COVID-19 vaccine came back as 95% effective. In her career conducting HIV clinical trials, she had never seen anything like it. Even HIV prevention methods she had studied that had worked, such as the dapivirine ring, had an overall efficacy of 30%.

The COVID-19 success story started to soften her views toward another vaccine trial she was helping to conduct, a trial in HIV that used the same platform as Johnson & Johnson’s successful COVID-19 vaccine.

“When the COVID vaccine was cracked so quickly and seemingly quite easily, I did start to think, ‘Well, maybe … maybe this will work for HIV,’ “ she said in an interview.

That turned out to be false hope. The National Institutes of Health (NIH) announced that the trial Dr. Gill was helping to conduct, HVTN 705, was stopping early because it hadn’t generated enough of an immune response in participants to justify continuing. It was the second HIV vaccine to fail in the last year. It’s also the latest in what has been a litany of disappointments in the attempt to boost the human immune system to fight HIV without the need for ongoing HIV treatment.

In HVTN 705, known as the Imbokodo study (imbokodo is a Zulu word that’s part of a saying about women being strong as rocks), researchers used the platform made up of a common cold virus, adenovirus 26, to deliver a computer-generated mosaic of HIV antigens to participants’ immune systems. That mosaic of antigens is meant to goose the immune system into recognizing HIV if it were exposed to it.

When HIV enters the body, it infiltrates immune cells and replicates within them. To the rest of the immune system, those cells still register as just typical T-cells. The rest of the immune system can’t see that the virus is spreading through the very cells meant to protect the body from illness. That, plus the armor of sugary glycoproteins encasing the virus, has made HIV nearly impervious to vaccination.

Then, those so-called “prime” shots were followed by a second shot that targets glycoprotein 140, on the most common HIV subtype (or clade) in Africa, clade C. In the Imbokodo trial, a total of 2,637 women from five sub-Saharan African countries received shots at baseline, 3 months, 6 months, and 1 year. Then researchers followed the women from month 7 to 2 years after their third dose, testing their blood to see if their immune systems had generated the immune response the vaccine was meant to induce – and whether such immune response was associated with lower rates of HIV.

When researchers looked at the first 2 years of data, they learned that the vaccine was safe. And they found a total of 114 new cases of HIV – 51 among women who received the vaccine and 63 among those who received a placebo. That’s a 25.2% efficacy rate – but it wasn’t statistically significant.

The results are frustrating, said Carl Dieffenbach, PhD, director of the AIDS division at the National Institute of Allergy and Infectious Diseases (NIAID). NIAID is one of the funders of the study.

“This [trial] is a little more confounding, in that there is this low level of statistically insignificant difference between vaccine and placebo that starts somewhere around month 9 and then just kind of indolently is maintained over the next 15 months,” he said in an interview. “That’s kind of frustrating. Does it mean there’s a signal or is this just chance? Because that’s what statistics tell us, not to believe your last data point.”

What this means for the future direction of vaccine research is unclear. A sister study to Imbokodo, called Mosaico, recently finished enrolling participants. Mosaico uses the same adenovirus 26 platform, but it’s loaded with different antigens and targets a different glycoprotein for a different HIV subtype. If that trial shows success, it could mean that the platform is right, but the targets in the Imbokodo vaccine were wrong.

Dr. Dieffenbach said that before NIAID decides what to do with Mosaico they’ve asked researchers to analyze the data on the people who did respond, to see if those people have some specific variant of HIV or some other biomarker that could be used to form the next iteration of an HIV vaccine candidate. Only after that will they make a decision about Mosaico.

But he added that it does make him wonder if vaccine approaches that rely on nonneutralizing antibodies like this one have a ceiling of effectiveness that’s just too low to alter the course of the epidemic.

“I think we’ve discovered that there’s not a floor to [these nonneutralizing approaches], but there probably is a ceiling,” he said. “I don’t know if we’re going to get better than” a 25%-29% efficacy rate with those approaches.

The Imbokodo findings reminded Mitchell Warren, executive director of the global HIV prevention nonprofit, AVAC, of the data released in January from the Antibody Mediated Prevention (AMP) trial. That trial pitted the broadly neutralizing antibody (bNAb) VCR01 against HIV – and mostly, it lost.

VCR01 worked only on HIV variants that 30% of participants had. But in those 30%, it was 75% effective at preventing HIV. Now you have Imbokodo, with its potential 25% activity against HIV, something that may have been a fluke. This, to Mr. Warren, requires a rethinking of the whole HIV vaccine enterprise while “doubling, tripling, quadrupling down” on the HIV prevention methods we know work, such as preexposure prophylaxis (PrEP).

Dr. Dieffenbach agreed. To clinicians, Dr. Dieffenbach said the message of this HIV vaccine trial is flush with urgency: “Get your HIV-negative, at-risk people on PrEP tomorrow.”

There are now two pills approved for HIV prevention, both of which have been found to be up to 99% effective when taken consistently. A third option, injectable cabotegravir (Vocabria), has been submitted to the Food and Drug Administration for approval. The federal Ready, Set, PrEP program makes the pill available for free for those who qualify, and recently the Biden administration reaffirmed that, under the Affordable Care Act, insurance companies should cover all costs associated with PrEP, including lab work and exam visits.

But for the 157 women who participated in the trial at Dr. Gill’s site in Masiphumelele, on the southwestern tip of South Africa, the trial was personal, said Jason Naidoo, community liaison officer at the Desmond Tutu HIV Foundation, which conducted a portion of the study. These were women whose parents, siblings, or children were living with HIV or had died from AIDS-defining illnesses, he said. Their lives were chaotic, traveling at a moment’s notice to hometowns on the Eastern Cape, an 11-hour car ride away – longer by bus – for traditional prayers, funerals, and other important events.

Mr. Naidoo remembers arranging buses for the women to return for scheduled clinic visits, leaving the Eastern Cape in the afternoon and arriving in Masiphumelele in the early morning hours, just to keep the clinic appointment. Then, they’d turn around and return east.

They did this for 3 years, he said.

“The fact that these participants have stuck to this and been dedicated amidst all of the chaos talks about their commitment to actually having a vaccine for HIV,” he said. “They know their own risk profile as young Black women in South Africa, and they understand the need for an intervention for the future generations.

“So you can understand the emotion and the sense of sadness, the disappointment – the incredible [dis]belief that this [the failure of the vaccine] could have happened, because the expectations are so, so high.”

For Dr. Gill, who is lead investigator for Imbokodo in Masiphumelele, the weariness toward vaccines is back. Another trial is underway for an HIV vaccine with a platform that was successful in COVID-19 – using messenger RNA (mRNA), like the Pfizer and Moderna COVID-19 vaccines did.

“I think we need to be careful,” she said, “thinking that the mRNA vaccines are going to crack it.”

Dr. Dieffenbach, Dr. Gill, and Mr. Naidoo have disclosed no relevant financial relationships. The study was funded by Janssen, a Johnson & Johnson company, with NIAID and the Bill and Melinda Gates Foundation.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

Headache was the most common adverse event (AE) people experienced in 72 weeks of taking the once-daily investigational two-drug HIV treatment islatravir (ISL; Merck) plus doravirine (DOR; Merck), and those AEs were short-lived and mild, according to a safety analysis presented at the International AIDS Society (IAS) Conference 2021.

That finding, combined with other data showing few changes in metabolic markers, is potentially good news for people living with HIV, inasmuch as two-drug regimens generally have fewer side effects than traditional three- or four-drug regimens, said Jean-Michel Molina, MD, PhD, of Sant-Louis and Lariboisière Hospitals, Paris, who previously presented efficacy data on the combination at the HIV Glasgow 2020 Virtual Conference.

“At this point, it’s encouraging,” Dr. Molina told this news organization. “Safety is good, efficacy seems good. But the data are limited, and it’s too early to tell.”

If it makes it to the clinic, IS/DOR would be the fourth two-drug regimen approved for HIV treatment, following the U.S. Food and Drug Administration approval of dolutegravir/lamivudine (Dovato), dolutegravir/rilpivirine (Juluca), and the monthly injectable cabotegravir long-acting/rilpivirine long-acting (Cabenuva).

DOR, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is currently approved and is part of the three-drug single-pill regimen Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate, DOR/3TC/TDF, Merck). ISL is still under development for treatment and prevention. Dr. Molina had previously presented data showing that 81.1% of people living with HIV maintained undetectable viral loads (defined as <50 copies/mL) compared to 80.6% of people who continued treatment with DOR/3TC/TDF. Data on ISL/DOR versus DOR/3TC/TDF for people new to HIV treatment were published May 14 in The Lancet HIV.

The ISL/DOR trial was designed to assess the safety of three doses of ISL with 100 mg of DOR – 0.25 mg, 0.75 mg, and 2.25 mg – as a daily treatment. The investigators randomly assigned 29, 30, and 31 participants, respectively, to each of the dual-therapy arms and 31 people to the DOR/3TC/TDF arm after a 24-week lead-in course of DOR/3TC/TDF. At week 60, everyone in the two-drug arms received 0.75 mg of ISL with DOR.

At HIV Glasgow, Dr. Molina didn’t present details about the safety profile of the two-drug combination. Douglas Cunningham, DO, a primary care provider at Pueblo Family Physicians, Phoenix, presented such data at IAS 2021. What he showed was that over the first 96 weeks of the trial, there were a total of 118 AEs among the 90 participants in the ISL plus DOR arms and 42 among the 31 participants in the three-drug regimen arm, but there were only seven drug-related AEs for people in the ISL plus DOR arm, and all of those occurred during the first 48 weeks. There were none from weeks 48 to 96.

In total, there were no drug-related serious AEs for ISL/DOR; there was one in the DOR/3TC/TDF arm. The most common AE was headache, which occurred in a total of 10 participants in the ISL/DOR arms. There were nine cases of vitamin D deficiency, eight cases of nausea, seven cases of arthralgia, diarrhea, sinus pain, and vomiting, and six cases each of anxiety and rash. Four people experienced pain in their extremities.

In the three-drug combination arm, side effects were far fewer – just 18 occurred in at least 10% of participants. The most common AE among people on the three-drug combination was diarrhea, which occurred in six participants. Nausea occurred in three; vomiting and headache in two; and there was one instance each of vitamin D deficiency, arthralgia, sinus pain, rash, and pain in extremities.

“The majority of these events were mild, transient, and not related to study drug,” Dr. Cunningham said.

Three ISL/DOR participants experienced an increase in fasting triglyceride level of >500-1,000 mg/dL, and six patients experienced grade 4 changes in creatine kinase level of ≥20 IU/L. Dr. Cunningham said that all but one of the cases of an increase in creatinine level were the result of physical exertion by the participants, and all of those changes were found to have resolved at future visits. The bottom line is that the two-drug combination was safe.

“In the islatravir and doravirine arm, there were no serious drug related serious AEs and no discontinuations due to drug-related AEs from week 48 to week 96,” said Dr. Cunningham. “Islatravir in combination with doravirine was generally well tolerated through week 96 with few drug-related AEs.”

Still, the value of this combination is unclear for Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust. She pointed out that the data are preliminary and that islatravir hasn’t yet been shown to lessen the chances of development of treatment-resistant mutations – a big deal for two-drug regimens, inasmuch as early attempts at using only two drugs resulted in incomplete suppression of the virus and resistance. Merck is planning a study of the combination in heavily pretreated individuals.

Merck presented data at IAS on another NNRTI, the investigational MK-8507, in combination with islatravir. MK-8507 has the potential to be used weekly instead of daily. Dr. Waters said she suspects that this trial is just a proof of concept of islatravir in combination with an NNRTI. Merck has signed an agreement with Gilead Sciences to co-develop islatravir with long-acting lenacapravir. Additionally, the two-drug combination of dolutegravir and lamivudine has been very successful.

“I’d be surprised if they developed islatravir/doravirine as a usable combo,” she said. “It’s just too soon to say. My personal view is that people are a bit too overoptimistic about it.”

The study was funded by Merck. Dr. Molina has received grants from Gilead Sciences, Merck, ViiV Healthcare, and Sanofi. Dr. Waters has received speaker or advisory fees during the past 2 years from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

A version of this article first appeared on Medscape.com.

Headache was the most common adverse event (AE) people experienced in 72 weeks of taking the once-daily investigational two-drug HIV treatment islatravir (ISL; Merck) plus doravirine (DOR; Merck), and those AEs were short-lived and mild, according to a safety analysis presented at the International AIDS Society (IAS) Conference 2021.

That finding, combined with other data showing few changes in metabolic markers, is potentially good news for people living with HIV, inasmuch as two-drug regimens generally have fewer side effects than traditional three- or four-drug regimens, said Jean-Michel Molina, MD, PhD, of Sant-Louis and Lariboisière Hospitals, Paris, who previously presented efficacy data on the combination at the HIV Glasgow 2020 Virtual Conference.

“At this point, it’s encouraging,” Dr. Molina told this news organization. “Safety is good, efficacy seems good. But the data are limited, and it’s too early to tell.”

If it makes it to the clinic, IS/DOR would be the fourth two-drug regimen approved for HIV treatment, following the U.S. Food and Drug Administration approval of dolutegravir/lamivudine (Dovato), dolutegravir/rilpivirine (Juluca), and the monthly injectable cabotegravir long-acting/rilpivirine long-acting (Cabenuva).

DOR, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is currently approved and is part of the three-drug single-pill regimen Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate, DOR/3TC/TDF, Merck). ISL is still under development for treatment and prevention. Dr. Molina had previously presented data showing that 81.1% of people living with HIV maintained undetectable viral loads (defined as <50 copies/mL) compared to 80.6% of people who continued treatment with DOR/3TC/TDF. Data on ISL/DOR versus DOR/3TC/TDF for people new to HIV treatment were published May 14 in The Lancet HIV.

The ISL/DOR trial was designed to assess the safety of three doses of ISL with 100 mg of DOR – 0.25 mg, 0.75 mg, and 2.25 mg – as a daily treatment. The investigators randomly assigned 29, 30, and 31 participants, respectively, to each of the dual-therapy arms and 31 people to the DOR/3TC/TDF arm after a 24-week lead-in course of DOR/3TC/TDF. At week 60, everyone in the two-drug arms received 0.75 mg of ISL with DOR.

At HIV Glasgow, Dr. Molina didn’t present details about the safety profile of the two-drug combination. Douglas Cunningham, DO, a primary care provider at Pueblo Family Physicians, Phoenix, presented such data at IAS 2021. What he showed was that over the first 96 weeks of the trial, there were a total of 118 AEs among the 90 participants in the ISL plus DOR arms and 42 among the 31 participants in the three-drug regimen arm, but there were only seven drug-related AEs for people in the ISL plus DOR arm, and all of those occurred during the first 48 weeks. There were none from weeks 48 to 96.

In total, there were no drug-related serious AEs for ISL/DOR; there was one in the DOR/3TC/TDF arm. The most common AE was headache, which occurred in a total of 10 participants in the ISL/DOR arms. There were nine cases of vitamin D deficiency, eight cases of nausea, seven cases of arthralgia, diarrhea, sinus pain, and vomiting, and six cases each of anxiety and rash. Four people experienced pain in their extremities.

In the three-drug combination arm, side effects were far fewer – just 18 occurred in at least 10% of participants. The most common AE among people on the three-drug combination was diarrhea, which occurred in six participants. Nausea occurred in three; vomiting and headache in two; and there was one instance each of vitamin D deficiency, arthralgia, sinus pain, rash, and pain in extremities.

“The majority of these events were mild, transient, and not related to study drug,” Dr. Cunningham said.

Three ISL/DOR participants experienced an increase in fasting triglyceride level of >500-1,000 mg/dL, and six patients experienced grade 4 changes in creatine kinase level of ≥20 IU/L. Dr. Cunningham said that all but one of the cases of an increase in creatinine level were the result of physical exertion by the participants, and all of those changes were found to have resolved at future visits. The bottom line is that the two-drug combination was safe.

“In the islatravir and doravirine arm, there were no serious drug related serious AEs and no discontinuations due to drug-related AEs from week 48 to week 96,” said Dr. Cunningham. “Islatravir in combination with doravirine was generally well tolerated through week 96 with few drug-related AEs.”

Still, the value of this combination is unclear for Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust. She pointed out that the data are preliminary and that islatravir hasn’t yet been shown to lessen the chances of development of treatment-resistant mutations – a big deal for two-drug regimens, inasmuch as early attempts at using only two drugs resulted in incomplete suppression of the virus and resistance. Merck is planning a study of the combination in heavily pretreated individuals.

Merck presented data at IAS on another NNRTI, the investigational MK-8507, in combination with islatravir. MK-8507 has the potential to be used weekly instead of daily. Dr. Waters said she suspects that this trial is just a proof of concept of islatravir in combination with an NNRTI. Merck has signed an agreement with Gilead Sciences to co-develop islatravir with long-acting lenacapravir. Additionally, the two-drug combination of dolutegravir and lamivudine has been very successful.

“I’d be surprised if they developed islatravir/doravirine as a usable combo,” she said. “It’s just too soon to say. My personal view is that people are a bit too overoptimistic about it.”

The study was funded by Merck. Dr. Molina has received grants from Gilead Sciences, Merck, ViiV Healthcare, and Sanofi. Dr. Waters has received speaker or advisory fees during the past 2 years from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

A version of this article first appeared on Medscape.com.

Headache was the most common adverse event (AE) people experienced in 72 weeks of taking the once-daily investigational two-drug HIV treatment islatravir (ISL; Merck) plus doravirine (DOR; Merck), and those AEs were short-lived and mild, according to a safety analysis presented at the International AIDS Society (IAS) Conference 2021.

That finding, combined with other data showing few changes in metabolic markers, is potentially good news for people living with HIV, inasmuch as two-drug regimens generally have fewer side effects than traditional three- or four-drug regimens, said Jean-Michel Molina, MD, PhD, of Sant-Louis and Lariboisière Hospitals, Paris, who previously presented efficacy data on the combination at the HIV Glasgow 2020 Virtual Conference.

“At this point, it’s encouraging,” Dr. Molina told this news organization. “Safety is good, efficacy seems good. But the data are limited, and it’s too early to tell.”

If it makes it to the clinic, IS/DOR would be the fourth two-drug regimen approved for HIV treatment, following the U.S. Food and Drug Administration approval of dolutegravir/lamivudine (Dovato), dolutegravir/rilpivirine (Juluca), and the monthly injectable cabotegravir long-acting/rilpivirine long-acting (Cabenuva).

DOR, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is currently approved and is part of the three-drug single-pill regimen Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate, DOR/3TC/TDF, Merck). ISL is still under development for treatment and prevention. Dr. Molina had previously presented data showing that 81.1% of people living with HIV maintained undetectable viral loads (defined as <50 copies/mL) compared to 80.6% of people who continued treatment with DOR/3TC/TDF. Data on ISL/DOR versus DOR/3TC/TDF for people new to HIV treatment were published May 14 in The Lancet HIV.

The ISL/DOR trial was designed to assess the safety of three doses of ISL with 100 mg of DOR – 0.25 mg, 0.75 mg, and 2.25 mg – as a daily treatment. The investigators randomly assigned 29, 30, and 31 participants, respectively, to each of the dual-therapy arms and 31 people to the DOR/3TC/TDF arm after a 24-week lead-in course of DOR/3TC/TDF. At week 60, everyone in the two-drug arms received 0.75 mg of ISL with DOR.

At HIV Glasgow, Dr. Molina didn’t present details about the safety profile of the two-drug combination. Douglas Cunningham, DO, a primary care provider at Pueblo Family Physicians, Phoenix, presented such data at IAS 2021. What he showed was that over the first 96 weeks of the trial, there were a total of 118 AEs among the 90 participants in the ISL plus DOR arms and 42 among the 31 participants in the three-drug regimen arm, but there were only seven drug-related AEs for people in the ISL plus DOR arm, and all of those occurred during the first 48 weeks. There were none from weeks 48 to 96.

In total, there were no drug-related serious AEs for ISL/DOR; there was one in the DOR/3TC/TDF arm. The most common AE was headache, which occurred in a total of 10 participants in the ISL/DOR arms. There were nine cases of vitamin D deficiency, eight cases of nausea, seven cases of arthralgia, diarrhea, sinus pain, and vomiting, and six cases each of anxiety and rash. Four people experienced pain in their extremities.

In the three-drug combination arm, side effects were far fewer – just 18 occurred in at least 10% of participants. The most common AE among people on the three-drug combination was diarrhea, which occurred in six participants. Nausea occurred in three; vomiting and headache in two; and there was one instance each of vitamin D deficiency, arthralgia, sinus pain, rash, and pain in extremities.

“The majority of these events were mild, transient, and not related to study drug,” Dr. Cunningham said.

Three ISL/DOR participants experienced an increase in fasting triglyceride level of >500-1,000 mg/dL, and six patients experienced grade 4 changes in creatine kinase level of ≥20 IU/L. Dr. Cunningham said that all but one of the cases of an increase in creatinine level were the result of physical exertion by the participants, and all of those changes were found to have resolved at future visits. The bottom line is that the two-drug combination was safe.

“In the islatravir and doravirine arm, there were no serious drug related serious AEs and no discontinuations due to drug-related AEs from week 48 to week 96,” said Dr. Cunningham. “Islatravir in combination with doravirine was generally well tolerated through week 96 with few drug-related AEs.”

Still, the value of this combination is unclear for Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust. She pointed out that the data are preliminary and that islatravir hasn’t yet been shown to lessen the chances of development of treatment-resistant mutations – a big deal for two-drug regimens, inasmuch as early attempts at using only two drugs resulted in incomplete suppression of the virus and resistance. Merck is planning a study of the combination in heavily pretreated individuals.

Merck presented data at IAS on another NNRTI, the investigational MK-8507, in combination with islatravir. MK-8507 has the potential to be used weekly instead of daily. Dr. Waters said she suspects that this trial is just a proof of concept of islatravir in combination with an NNRTI. Merck has signed an agreement with Gilead Sciences to co-develop islatravir with long-acting lenacapravir. Additionally, the two-drug combination of dolutegravir and lamivudine has been very successful.

“I’d be surprised if they developed islatravir/doravirine as a usable combo,” she said. “It’s just too soon to say. My personal view is that people are a bit too overoptimistic about it.”

The study was funded by Merck. Dr. Molina has received grants from Gilead Sciences, Merck, ViiV Healthcare, and Sanofi. Dr. Waters has received speaker or advisory fees during the past 2 years from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

A version of this article first appeared on Medscape.com.

HIV increases the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%, according to a report from the World Health Organization on COVID-19 outcomes among people living with HIV. The study primarily included people from South Africa but also some data from other parts of the world, including the United States.

However, the report, presented at the 11th IAS Conference on HIV Science (IAS 2021), couldn’t answer some crucial questions clinicians have been wondering about since the COVID-19 pandemic began. For example, was the increase in COVID risk a result of the presence of HIV or because of the immune compromise caused by untreated HIV?

The report didn’t include data on viral load or CD counts, both used to evaluate the health of a person’s immune system. On effective treatment, people living with HIV have a lifespan close to their HIV-negative peers. And effective treatment causes undetectable viral loads which, when maintained for 6 months or more, eliminates transmission of HIV to sexual partners.

What’s clear is that in people with HIV, as in people without HIV, older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes and were most likely to die from COVID-19.

For David Malebranche, MD, MPH, an internal medicine doctor who provides primary care for people in Atlanta, and who was not involved in the study, the WHO study didn’t add anything new. He already recommends the COVID-19 vaccine for all of his patients, HIV-positive or not.

“We don’t have any information from this about the T-cell counts [or] the rates of viral suppression, which I think is tremendously important,” he told this news organization. “To bypass that and not include that in any of the discussion puts the results in a questionable place for me.”

The results come from the WHO Clinical Platform, which culls data from WHO member country surveillance as well as manual case reports from all over the world. By April 29, data on 268,412 people hospitalized with COVID-19 from 37 countries were reported to the platform. Of those, 22,640 people are from the U.S.

A total of 15,522 participants worldwide were living with HIV, 664 in the United States. All U.S. cases were reported from the New York City Health and Hospitals system, Henry Ford Hospital in Detroit, and BronxCare Health System in New York City. Almost all of the remaining participants lived in South Africa – 14,682 of the 15,522, or 94.5%.

Of the 15,522 people living with HIV in the overall group, 37.1% of participants were male, and their median age was 45 years. More than 1 in 3 (36.2%) were admitted with severe or critical COVID-19, and nearly one quarter – 23.1% – with a known outcome died. More than half had one or more chronic conditions, including those that themselves are associated with worse COVID-19 outcomes, such as hypertension (in 33.2% of the participants), diabetes (22.7%), and BMIs above 30 (16.9%). In addition, 8.9% were smokers, 6.6% had chronic pulmonary disease, and 4.3% had chronic heart disease.

After adjusting for those chronic conditions, age, and sex, people living with HIV had a 6% higher rate of severe or critical COVID-19 illness. When investigators adjusted the analysis additionally to differentiate outcomes based on not just the presence of comorbid conditions but the number of them a person had, that increased risk rose to 13%. HIV itself is a comorbid condition, though it wasn’t counted as one in this adjusted analysis.

It didn’t matter whether researchers looked at risk for severe outcomes or deaths after removing the significant co-occurring conditions or if they looked at number of chronic illnesses (aside from HIV), said Silvia Bertagnolio, MD, medical officer at the World Health Organization and co-author of the analysis.

“Both models show almost identical [adjusted odds ratios], meaning that HIV was independently significantly associated with severe/critical presentation,” she told this news organization.

As for death, the analysis showed that, overall, people living with HIV were 30% more likely to die of COVID-19 compared with those not living with HIV. And while this held true even when they adjusted the data for comorbidities, people with HIV were more likely to die if they were over age 65 (risk increased by 82%), male (risk increased by 21%), had diabetes (risk increased by 50%), or had hypertension (risk increased by 26%).

When they broke down the data by WHO region – Africa, Europe, the Americas – investigators found that the increased risk for death held true in Africa. But there were not enough data from the other regions to model mortality risk. What’s more, when they broke the data down by country and excluded South Africa, they found that the elevated risk for death in people living with HIV did not reach statistical significance. Dr. Bertagnolio said she suspects that the small sample sizes from other regions made it impossible to detect a difference, but one could still be present.

One thing conspicuously absent from the analysis was information on viral load, CD4 T-cell count, progression of HIV to AIDS, and whether individuals were in HIV care. The first three factors were not reported in the platform, and the fourth was available for 60% of participants but was not included in the analysis. Dr. Bertagnolio pointed out that, for those 60% of participants, 91.8% were on antiretroviral treatment (ART).

“The majority of patients come from South Africa, and we know that in South Africa, over 90% of people receiving ART are virologically suppressed,” she told this news organization. “So we could speculate that this effect persists despite the use of ART, in a population likely to be virally suppressed, although we cannot assess this with certainty through the data set we had.”

A much smaller study of 749 people living with HIV and diagnosed with SARS-CoV-2, also presented at the conference, found that detectable HIV viral load was significantly associated with a slightly higher risk of severe outcomes (P < .039), but CD4 counts less than 200 cells/mm³ was not (P = .15).

And although both Dr. Bertagnolio and conference organizers presented this data as proof that HIV increases the risk for poor COVID-19 outcomes, Dr. Malebranche isn’t so sure. He estimates that only about half his patients have received the COVID-19 vaccine. But this study is unlikely to make him forcefully recommend a COVID-19 vaccination with young, otherwise healthy, and undetectable people in his care who express particular concern about long-term effects of the vaccine. He also manages a lot of people with HIV who have undetectable viral loads and CD4 counts of up to 1,200 but are older, with diabetes, obesity, and high blood pressure. Those are the people he will target with stronger messages regarding the vaccine.

“The young patients who are healthy, virally suppressed, and doing well may very much argue with me, ‘I’m not going to push it,’ but I will bring it up on the next visit,” he said. The analysis “just helps reinforce in me that I need to have these conversations and be a little bit more persuasive to my older patients with comorbid conditions.”

Dr. Bertagnolio has disclosed no relevant financial relationships. Dr. Malebranche serves on the pre-exposure prophylaxis (PrEP) speakers bureau for Gilead Sciences and has consulted and advised for ViiV Healthcare. This study was funded by the World Health Organization.

A version of this article first appeared on Medscape.com.

HIV increases the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%, according to a report from the World Health Organization on COVID-19 outcomes among people living with HIV. The study primarily included people from South Africa but also some data from other parts of the world, including the United States.

However, the report, presented at the 11th IAS Conference on HIV Science (IAS 2021), couldn’t answer some crucial questions clinicians have been wondering about since the COVID-19 pandemic began. For example, was the increase in COVID risk a result of the presence of HIV or because of the immune compromise caused by untreated HIV?

The report didn’t include data on viral load or CD counts, both used to evaluate the health of a person’s immune system. On effective treatment, people living with HIV have a lifespan close to their HIV-negative peers. And effective treatment causes undetectable viral loads which, when maintained for 6 months or more, eliminates transmission of HIV to sexual partners.

What’s clear is that in people with HIV, as in people without HIV, older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes and were most likely to die from COVID-19.

For David Malebranche, MD, MPH, an internal medicine doctor who provides primary care for people in Atlanta, and who was not involved in the study, the WHO study didn’t add anything new. He already recommends the COVID-19 vaccine for all of his patients, HIV-positive or not.

“We don’t have any information from this about the T-cell counts [or] the rates of viral suppression, which I think is tremendously important,” he told this news organization. “To bypass that and not include that in any of the discussion puts the results in a questionable place for me.”

The results come from the WHO Clinical Platform, which culls data from WHO member country surveillance as well as manual case reports from all over the world. By April 29, data on 268,412 people hospitalized with COVID-19 from 37 countries were reported to the platform. Of those, 22,640 people are from the U.S.

A total of 15,522 participants worldwide were living with HIV, 664 in the United States. All U.S. cases were reported from the New York City Health and Hospitals system, Henry Ford Hospital in Detroit, and BronxCare Health System in New York City. Almost all of the remaining participants lived in South Africa – 14,682 of the 15,522, or 94.5%.

Of the 15,522 people living with HIV in the overall group, 37.1% of participants were male, and their median age was 45 years. More than 1 in 3 (36.2%) were admitted with severe or critical COVID-19, and nearly one quarter – 23.1% – with a known outcome died. More than half had one or more chronic conditions, including those that themselves are associated with worse COVID-19 outcomes, such as hypertension (in 33.2% of the participants), diabetes (22.7%), and BMIs above 30 (16.9%). In addition, 8.9% were smokers, 6.6% had chronic pulmonary disease, and 4.3% had chronic heart disease.

After adjusting for those chronic conditions, age, and sex, people living with HIV had a 6% higher rate of severe or critical COVID-19 illness. When investigators adjusted the analysis additionally to differentiate outcomes based on not just the presence of comorbid conditions but the number of them a person had, that increased risk rose to 13%. HIV itself is a comorbid condition, though it wasn’t counted as one in this adjusted analysis.

It didn’t matter whether researchers looked at risk for severe outcomes or deaths after removing the significant co-occurring conditions or if they looked at number of chronic illnesses (aside from HIV), said Silvia Bertagnolio, MD, medical officer at the World Health Organization and co-author of the analysis.

“Both models show almost identical [adjusted odds ratios], meaning that HIV was independently significantly associated with severe/critical presentation,” she told this news organization.

As for death, the analysis showed that, overall, people living with HIV were 30% more likely to die of COVID-19 compared with those not living with HIV. And while this held true even when they adjusted the data for comorbidities, people with HIV were more likely to die if they were over age 65 (risk increased by 82%), male (risk increased by 21%), had diabetes (risk increased by 50%), or had hypertension (risk increased by 26%).

When they broke down the data by WHO region – Africa, Europe, the Americas – investigators found that the increased risk for death held true in Africa. But there were not enough data from the other regions to model mortality risk. What’s more, when they broke the data down by country and excluded South Africa, they found that the elevated risk for death in people living with HIV did not reach statistical significance. Dr. Bertagnolio said she suspects that the small sample sizes from other regions made it impossible to detect a difference, but one could still be present.

One thing conspicuously absent from the analysis was information on viral load, CD4 T-cell count, progression of HIV to AIDS, and whether individuals were in HIV care. The first three factors were not reported in the platform, and the fourth was available for 60% of participants but was not included in the analysis. Dr. Bertagnolio pointed out that, for those 60% of participants, 91.8% were on antiretroviral treatment (ART).

“The majority of patients come from South Africa, and we know that in South Africa, over 90% of people receiving ART are virologically suppressed,” she told this news organization. “So we could speculate that this effect persists despite the use of ART, in a population likely to be virally suppressed, although we cannot assess this with certainty through the data set we had.”

A much smaller study of 749 people living with HIV and diagnosed with SARS-CoV-2, also presented at the conference, found that detectable HIV viral load was significantly associated with a slightly higher risk of severe outcomes (P < .039), but CD4 counts less than 200 cells/mm³ was not (P = .15).

And although both Dr. Bertagnolio and conference organizers presented this data as proof that HIV increases the risk for poor COVID-19 outcomes, Dr. Malebranche isn’t so sure. He estimates that only about half his patients have received the COVID-19 vaccine. But this study is unlikely to make him forcefully recommend a COVID-19 vaccination with young, otherwise healthy, and undetectable people in his care who express particular concern about long-term effects of the vaccine. He also manages a lot of people with HIV who have undetectable viral loads and CD4 counts of up to 1,200 but are older, with diabetes, obesity, and high blood pressure. Those are the people he will target with stronger messages regarding the vaccine.

“The young patients who are healthy, virally suppressed, and doing well may very much argue with me, ‘I’m not going to push it,’ but I will bring it up on the next visit,” he said. The analysis “just helps reinforce in me that I need to have these conversations and be a little bit more persuasive to my older patients with comorbid conditions.”

Dr. Bertagnolio has disclosed no relevant financial relationships. Dr. Malebranche serves on the pre-exposure prophylaxis (PrEP) speakers bureau for Gilead Sciences and has consulted and advised for ViiV Healthcare. This study was funded by the World Health Organization.

A version of this article first appeared on Medscape.com.

HIV increases the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%, according to a report from the World Health Organization on COVID-19 outcomes among people living with HIV. The study primarily included people from South Africa but also some data from other parts of the world, including the United States.

However, the report, presented at the 11th IAS Conference on HIV Science (IAS 2021), couldn’t answer some crucial questions clinicians have been wondering about since the COVID-19 pandemic began. For example, was the increase in COVID risk a result of the presence of HIV or because of the immune compromise caused by untreated HIV?

The report didn’t include data on viral load or CD counts, both used to evaluate the health of a person’s immune system. On effective treatment, people living with HIV have a lifespan close to their HIV-negative peers. And effective treatment causes undetectable viral loads which, when maintained for 6 months or more, eliminates transmission of HIV to sexual partners.

What’s clear is that in people with HIV, as in people without HIV, older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes and were most likely to die from COVID-19.

For David Malebranche, MD, MPH, an internal medicine doctor who provides primary care for people in Atlanta, and who was not involved in the study, the WHO study didn’t add anything new. He already recommends the COVID-19 vaccine for all of his patients, HIV-positive or not.

“We don’t have any information from this about the T-cell counts [or] the rates of viral suppression, which I think is tremendously important,” he told this news organization. “To bypass that and not include that in any of the discussion puts the results in a questionable place for me.”

The results come from the WHO Clinical Platform, which culls data from WHO member country surveillance as well as manual case reports from all over the world. By April 29, data on 268,412 people hospitalized with COVID-19 from 37 countries were reported to the platform. Of those, 22,640 people are from the U.S.

A total of 15,522 participants worldwide were living with HIV, 664 in the United States. All U.S. cases were reported from the New York City Health and Hospitals system, Henry Ford Hospital in Detroit, and BronxCare Health System in New York City. Almost all of the remaining participants lived in South Africa – 14,682 of the 15,522, or 94.5%.

Of the 15,522 people living with HIV in the overall group, 37.1% of participants were male, and their median age was 45 years. More than 1 in 3 (36.2%) were admitted with severe or critical COVID-19, and nearly one quarter – 23.1% – with a known outcome died. More than half had one or more chronic conditions, including those that themselves are associated with worse COVID-19 outcomes, such as hypertension (in 33.2% of the participants), diabetes (22.7%), and BMIs above 30 (16.9%). In addition, 8.9% were smokers, 6.6% had chronic pulmonary disease, and 4.3% had chronic heart disease.

After adjusting for those chronic conditions, age, and sex, people living with HIV had a 6% higher rate of severe or critical COVID-19 illness. When investigators adjusted the analysis additionally to differentiate outcomes based on not just the presence of comorbid conditions but the number of them a person had, that increased risk rose to 13%. HIV itself is a comorbid condition, though it wasn’t counted as one in this adjusted analysis.

It didn’t matter whether researchers looked at risk for severe outcomes or deaths after removing the significant co-occurring conditions or if they looked at number of chronic illnesses (aside from HIV), said Silvia Bertagnolio, MD, medical officer at the World Health Organization and co-author of the analysis.

“Both models show almost identical [adjusted odds ratios], meaning that HIV was independently significantly associated with severe/critical presentation,” she told this news organization.

As for death, the analysis showed that, overall, people living with HIV were 30% more likely to die of COVID-19 compared with those not living with HIV. And while this held true even when they adjusted the data for comorbidities, people with HIV were more likely to die if they were over age 65 (risk increased by 82%), male (risk increased by 21%), had diabetes (risk increased by 50%), or had hypertension (risk increased by 26%).

When they broke down the data by WHO region – Africa, Europe, the Americas – investigators found that the increased risk for death held true in Africa. But there were not enough data from the other regions to model mortality risk. What’s more, when they broke the data down by country and excluded South Africa, they found that the elevated risk for death in people living with HIV did not reach statistical significance. Dr. Bertagnolio said she suspects that the small sample sizes from other regions made it impossible to detect a difference, but one could still be present.

One thing conspicuously absent from the analysis was information on viral load, CD4 T-cell count, progression of HIV to AIDS, and whether individuals were in HIV care. The first three factors were not reported in the platform, and the fourth was available for 60% of participants but was not included in the analysis. Dr. Bertagnolio pointed out that, for those 60% of participants, 91.8% were on antiretroviral treatment (ART).

“The majority of patients come from South Africa, and we know that in South Africa, over 90% of people receiving ART are virologically suppressed,” she told this news organization. “So we could speculate that this effect persists despite the use of ART, in a population likely to be virally suppressed, although we cannot assess this with certainty through the data set we had.”

A much smaller study of 749 people living with HIV and diagnosed with SARS-CoV-2, also presented at the conference, found that detectable HIV viral load was significantly associated with a slightly higher risk of severe outcomes (P < .039), but CD4 counts less than 200 cells/mm³ was not (P = .15).

And although both Dr. Bertagnolio and conference organizers presented this data as proof that HIV increases the risk for poor COVID-19 outcomes, Dr. Malebranche isn’t so sure. He estimates that only about half his patients have received the COVID-19 vaccine. But this study is unlikely to make him forcefully recommend a COVID-19 vaccination with young, otherwise healthy, and undetectable people in his care who express particular concern about long-term effects of the vaccine. He also manages a lot of people with HIV who have undetectable viral loads and CD4 counts of up to 1,200 but are older, with diabetes, obesity, and high blood pressure. Those are the people he will target with stronger messages regarding the vaccine.

“The young patients who are healthy, virally suppressed, and doing well may very much argue with me, ‘I’m not going to push it,’ but I will bring it up on the next visit,” he said. The analysis “just helps reinforce in me that I need to have these conversations and be a little bit more persuasive to my older patients with comorbid conditions.”

Dr. Bertagnolio has disclosed no relevant financial relationships. Dr. Malebranche serves on the pre-exposure prophylaxis (PrEP) speakers bureau for Gilead Sciences and has consulted and advised for ViiV Healthcare. This study was funded by the World Health Organization.

A version of this article first appeared on Medscape.com.