Infectious Diseases

In creating a guide about monkeypox for ob.gyns., Denise J. Jamieson, MD, MPH, turned to research she relied on during another outbreak of the disease nearly 20 years ago.

Dr. Jamieson, the James Robert McCord Professor and chair of the department of gynecology and obstetrics at Emory Healthcare, Atlanta, had been working for the Centers for Disease Control and Prevention in 2003 when doctors diagnosed monkeypox in several states.

That year, the virus was mainly transmitted by contact with pet prairie dogs, including in childcare and school settings. Of the approximately 70 suspected and confirmed cases, 55% occurred in female patients, according to one study .

Dr. Jamieson, an obstetrician with a focus on emerging infectious diseases, and colleagues at the agency published a commentary in Obstetrics & Gynecology highlighting the need for physicians to stay up to date with relevant information about the virus.

Fast forward to 2022: Dr. Jamieson – again with coauthors from the CDC – is delivering a similar message in the same journal about the need for clinicians to be prepared for this virus.

“Most ob.gyns. have never seen a case of monkeypox virus infection and may not be aware of testing, treatment, or pre-exposure or postexposure vaccine options,” she and her coauthors wrote in a primer published online.

But if a woman were to contract the virus, her ob.gyn. might well be the first clinician she called. “We are often the first people, the first physicians to see and evaluate women with various symptoms,” Dr. Jamieson said.

To promptly diagnose, treat, and prevent further spread of monkeypox, ob.gyns. need up-to-date information, Dr. Jamieson and colleagues said.

Based on data from related viruses like smallpox, monkeypox may be more severe in pregnant women and entail risk for adverse pregnancy outcomes, Dr. Jamieson said.
 

Outliers

So far this year, monkeypox has predominantly spread among men who have sex with men. Cases have occurred in women, however, some of whom have required hospitalization.

According to the CDC, as of July 25, 1,373 cases of monkeypox in the United States were in men and 13 in women. The total confirmed case count exceeded 5,800 as of Aug. 1. The agency recently announced that it planned to make the disease a reportable condition.

In the United Kingdom, which has been hit hard by the outbreak, researchers are keeping a close eye on the number of cases in women to assess how the disease is spreading.

At least one case of monkeypox in the United States has occurred in a pregnant woman who delivered. The mother and baby, who received immune globulin as a preventive measure, are doing well, according to health officials.  

“We know that infection can occur through placental transfer. In the case that we are aware of presently, it does not appear that the virus was transmitted,” said John T. Brooks, MD, the CDC’s chief medical officer in the division of HIV prevention, on a July 23 call with clinicians.

While monkeypox can be transmitted in utero and during sexual activity, it also can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC.
 

A preferred vaccine and antiviral in pregnancy

One monkeypox vaccine, Jynneos, is preferred for use during pregnancy, while another, ACAM2000, is contraindicated, the CDC advises.

Jynneos can be offered to people who are pregnant or breastfeeding who are eligible for vaccination based on confirmed or likely contact with cases, ideally within 4 days of exposure. People at high risk for exposure, such as laboratory workers, may receive the vaccine in advance.

Developmental toxicity studies in animals showed no evidence of harm with the Jynneos vaccine, Dr. Jamieson said.

ACAM2000, however, can cause fetal vaccinia and should not be used in people who are pregnant or breastfeeding, according to the CDC.

The Society for Maternal-Fetal Medicine notes that, if treatment for monkeypox is warranted, tecovirimat should be considered the first-line antiviral for pregnant, recently pregnant, and breastfeeding people, in line with CDC guidance.
 

Current outbreak ‘very different,’ but lessons apply

In 2003, some women exposed to monkeypox through contact with infected prairie dogs were pregnant – which is how Dr. Jamieson came to be involved in responding to the outbreak and studying the effects of the virus in pregnancy.

“When this resurfaced this year, of course it caught my attention,” Dr. Jamieson said. The extensive person-to-person transmission and far greater number of cases today make the current outbreak “very different” from the prior one, she said.

But key principles in managing the disease and understanding its potential risks in pregnancy – despite relatively limited information – remain the same.

“Whenever you are looking at an infectious disease, you want to think about, are pregnant persons more susceptible or more likely to have severe disease,” Dr. Jamieson said. Smallpox, a similar orthopoxvirus, “is more severe during pregnancy with a higher case fatality rate,” which is one reason for concern with monkeypox in this population.

In terms of pregnancy outcomes, researchers have data from only a handful of confirmed cases of monkeypox, which makes it difficult to draw conclusions, Dr. Jamieson said. A review of five cases from outside the United States in prior years found that three resulted in loss of the pregnancy. One resulted in preterm delivery of an infant who subsequently died. One child was apparently healthy and born at term.
 

Addition to the differential diagnosis

A separate team of researchers has proposed a clinical management algorithm for pregnant women with suspected exposure to monkeypox.

“Clinicians must maintain a high index of suspicion for monkeypox virus in any pregnant woman presenting with lymphadenopathy and vesiculopustular rash – including rash localized to the genital or perianal region – even if there are no apparent epidemiological links,” Pradip Dashraath, MBBS, National University Hospital, Singapore, and coauthors wrote in The Lancet.

Jamieson echoed the call for increased vigilance.

“As ob.gyns., people may present to us with genital lesions concerning for sexually transmitted infection. And it is important to include monkeypox in our differential,” Dr. Jamieson said. “We are trying to get the word out that it needs to be part of what you think about when you see a patient with genital ulcers.”

Health care professionals have acquired monkeypox through contact with patients or fomites, so clinicians should be sure to use appropriate precautions when evaluating patients who might have monkeypox, Dr. Jamieson added. Appropriate protective measures include wearing a gown, gloves, eye protection, and an N95.

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

In creating a guide about monkeypox for ob.gyns., Denise J. Jamieson, MD, MPH, turned to research she relied on during another outbreak of the disease nearly 20 years ago.

Dr. Jamieson, the James Robert McCord Professor and chair of the department of gynecology and obstetrics at Emory Healthcare, Atlanta, had been working for the Centers for Disease Control and Prevention in 2003 when doctors diagnosed monkeypox in several states.

That year, the virus was mainly transmitted by contact with pet prairie dogs, including in childcare and school settings. Of the approximately 70 suspected and confirmed cases, 55% occurred in female patients, according to one study .

Dr. Jamieson, an obstetrician with a focus on emerging infectious diseases, and colleagues at the agency published a commentary in Obstetrics & Gynecology highlighting the need for physicians to stay up to date with relevant information about the virus.

Fast forward to 2022: Dr. Jamieson – again with coauthors from the CDC – is delivering a similar message in the same journal about the need for clinicians to be prepared for this virus.

“Most ob.gyns. have never seen a case of monkeypox virus infection and may not be aware of testing, treatment, or pre-exposure or postexposure vaccine options,” she and her coauthors wrote in a primer published online.

But if a woman were to contract the virus, her ob.gyn. might well be the first clinician she called. “We are often the first people, the first physicians to see and evaluate women with various symptoms,” Dr. Jamieson said.

To promptly diagnose, treat, and prevent further spread of monkeypox, ob.gyns. need up-to-date information, Dr. Jamieson and colleagues said.

Based on data from related viruses like smallpox, monkeypox may be more severe in pregnant women and entail risk for adverse pregnancy outcomes, Dr. Jamieson said.
 

Outliers

So far this year, monkeypox has predominantly spread among men who have sex with men. Cases have occurred in women, however, some of whom have required hospitalization.

According to the CDC, as of July 25, 1,373 cases of monkeypox in the United States were in men and 13 in women. The total confirmed case count exceeded 5,800 as of Aug. 1. The agency recently announced that it planned to make the disease a reportable condition.

In the United Kingdom, which has been hit hard by the outbreak, researchers are keeping a close eye on the number of cases in women to assess how the disease is spreading.

At least one case of monkeypox in the United States has occurred in a pregnant woman who delivered. The mother and baby, who received immune globulin as a preventive measure, are doing well, according to health officials.  

“We know that infection can occur through placental transfer. In the case that we are aware of presently, it does not appear that the virus was transmitted,” said John T. Brooks, MD, the CDC’s chief medical officer in the division of HIV prevention, on a July 23 call with clinicians.

While monkeypox can be transmitted in utero and during sexual activity, it also can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC.
 

A preferred vaccine and antiviral in pregnancy

One monkeypox vaccine, Jynneos, is preferred for use during pregnancy, while another, ACAM2000, is contraindicated, the CDC advises.

Jynneos can be offered to people who are pregnant or breastfeeding who are eligible for vaccination based on confirmed or likely contact with cases, ideally within 4 days of exposure. People at high risk for exposure, such as laboratory workers, may receive the vaccine in advance.

Developmental toxicity studies in animals showed no evidence of harm with the Jynneos vaccine, Dr. Jamieson said.

ACAM2000, however, can cause fetal vaccinia and should not be used in people who are pregnant or breastfeeding, according to the CDC.

The Society for Maternal-Fetal Medicine notes that, if treatment for monkeypox is warranted, tecovirimat should be considered the first-line antiviral for pregnant, recently pregnant, and breastfeeding people, in line with CDC guidance.
 

Current outbreak ‘very different,’ but lessons apply

In 2003, some women exposed to monkeypox through contact with infected prairie dogs were pregnant – which is how Dr. Jamieson came to be involved in responding to the outbreak and studying the effects of the virus in pregnancy.

“When this resurfaced this year, of course it caught my attention,” Dr. Jamieson said. The extensive person-to-person transmission and far greater number of cases today make the current outbreak “very different” from the prior one, she said.

But key principles in managing the disease and understanding its potential risks in pregnancy – despite relatively limited information – remain the same.

“Whenever you are looking at an infectious disease, you want to think about, are pregnant persons more susceptible or more likely to have severe disease,” Dr. Jamieson said. Smallpox, a similar orthopoxvirus, “is more severe during pregnancy with a higher case fatality rate,” which is one reason for concern with monkeypox in this population.

In terms of pregnancy outcomes, researchers have data from only a handful of confirmed cases of monkeypox, which makes it difficult to draw conclusions, Dr. Jamieson said. A review of five cases from outside the United States in prior years found that three resulted in loss of the pregnancy. One resulted in preterm delivery of an infant who subsequently died. One child was apparently healthy and born at term.
 

Addition to the differential diagnosis

A separate team of researchers has proposed a clinical management algorithm for pregnant women with suspected exposure to monkeypox.

“Clinicians must maintain a high index of suspicion for monkeypox virus in any pregnant woman presenting with lymphadenopathy and vesiculopustular rash – including rash localized to the genital or perianal region – even if there are no apparent epidemiological links,” Pradip Dashraath, MBBS, National University Hospital, Singapore, and coauthors wrote in The Lancet.

Jamieson echoed the call for increased vigilance.

“As ob.gyns., people may present to us with genital lesions concerning for sexually transmitted infection. And it is important to include monkeypox in our differential,” Dr. Jamieson said. “We are trying to get the word out that it needs to be part of what you think about when you see a patient with genital ulcers.”

Health care professionals have acquired monkeypox through contact with patients or fomites, so clinicians should be sure to use appropriate precautions when evaluating patients who might have monkeypox, Dr. Jamieson added. Appropriate protective measures include wearing a gown, gloves, eye protection, and an N95.

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

In creating a guide about monkeypox for ob.gyns., Denise J. Jamieson, MD, MPH, turned to research she relied on during another outbreak of the disease nearly 20 years ago.

Dr. Jamieson, the James Robert McCord Professor and chair of the department of gynecology and obstetrics at Emory Healthcare, Atlanta, had been working for the Centers for Disease Control and Prevention in 2003 when doctors diagnosed monkeypox in several states.

That year, the virus was mainly transmitted by contact with pet prairie dogs, including in childcare and school settings. Of the approximately 70 suspected and confirmed cases, 55% occurred in female patients, according to one study .

Dr. Jamieson, an obstetrician with a focus on emerging infectious diseases, and colleagues at the agency published a commentary in Obstetrics & Gynecology highlighting the need for physicians to stay up to date with relevant information about the virus.

Fast forward to 2022: Dr. Jamieson – again with coauthors from the CDC – is delivering a similar message in the same journal about the need for clinicians to be prepared for this virus.

“Most ob.gyns. have never seen a case of monkeypox virus infection and may not be aware of testing, treatment, or pre-exposure or postexposure vaccine options,” she and her coauthors wrote in a primer published online.

But if a woman were to contract the virus, her ob.gyn. might well be the first clinician she called. “We are often the first people, the first physicians to see and evaluate women with various symptoms,” Dr. Jamieson said.

To promptly diagnose, treat, and prevent further spread of monkeypox, ob.gyns. need up-to-date information, Dr. Jamieson and colleagues said.

Based on data from related viruses like smallpox, monkeypox may be more severe in pregnant women and entail risk for adverse pregnancy outcomes, Dr. Jamieson said.
 

Outliers

So far this year, monkeypox has predominantly spread among men who have sex with men. Cases have occurred in women, however, some of whom have required hospitalization.

According to the CDC, as of July 25, 1,373 cases of monkeypox in the United States were in men and 13 in women. The total confirmed case count exceeded 5,800 as of Aug. 1. The agency recently announced that it planned to make the disease a reportable condition.

In the United Kingdom, which has been hit hard by the outbreak, researchers are keeping a close eye on the number of cases in women to assess how the disease is spreading.

At least one case of monkeypox in the United States has occurred in a pregnant woman who delivered. The mother and baby, who received immune globulin as a preventive measure, are doing well, according to health officials.  

“We know that infection can occur through placental transfer. In the case that we are aware of presently, it does not appear that the virus was transmitted,” said John T. Brooks, MD, the CDC’s chief medical officer in the division of HIV prevention, on a July 23 call with clinicians.

While monkeypox can be transmitted in utero and during sexual activity, it also can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC.
 

A preferred vaccine and antiviral in pregnancy

One monkeypox vaccine, Jynneos, is preferred for use during pregnancy, while another, ACAM2000, is contraindicated, the CDC advises.

Jynneos can be offered to people who are pregnant or breastfeeding who are eligible for vaccination based on confirmed or likely contact with cases, ideally within 4 days of exposure. People at high risk for exposure, such as laboratory workers, may receive the vaccine in advance.

Developmental toxicity studies in animals showed no evidence of harm with the Jynneos vaccine, Dr. Jamieson said.

ACAM2000, however, can cause fetal vaccinia and should not be used in people who are pregnant or breastfeeding, according to the CDC.

The Society for Maternal-Fetal Medicine notes that, if treatment for monkeypox is warranted, tecovirimat should be considered the first-line antiviral for pregnant, recently pregnant, and breastfeeding people, in line with CDC guidance.
 

Current outbreak ‘very different,’ but lessons apply

In 2003, some women exposed to monkeypox through contact with infected prairie dogs were pregnant – which is how Dr. Jamieson came to be involved in responding to the outbreak and studying the effects of the virus in pregnancy.

“When this resurfaced this year, of course it caught my attention,” Dr. Jamieson said. The extensive person-to-person transmission and far greater number of cases today make the current outbreak “very different” from the prior one, she said.

But key principles in managing the disease and understanding its potential risks in pregnancy – despite relatively limited information – remain the same.

“Whenever you are looking at an infectious disease, you want to think about, are pregnant persons more susceptible or more likely to have severe disease,” Dr. Jamieson said. Smallpox, a similar orthopoxvirus, “is more severe during pregnancy with a higher case fatality rate,” which is one reason for concern with monkeypox in this population.

In terms of pregnancy outcomes, researchers have data from only a handful of confirmed cases of monkeypox, which makes it difficult to draw conclusions, Dr. Jamieson said. A review of five cases from outside the United States in prior years found that three resulted in loss of the pregnancy. One resulted in preterm delivery of an infant who subsequently died. One child was apparently healthy and born at term.
 

Addition to the differential diagnosis

A separate team of researchers has proposed a clinical management algorithm for pregnant women with suspected exposure to monkeypox.

“Clinicians must maintain a high index of suspicion for monkeypox virus in any pregnant woman presenting with lymphadenopathy and vesiculopustular rash – including rash localized to the genital or perianal region – even if there are no apparent epidemiological links,” Pradip Dashraath, MBBS, National University Hospital, Singapore, and coauthors wrote in The Lancet.

Jamieson echoed the call for increased vigilance.

“As ob.gyns., people may present to us with genital lesions concerning for sexually transmitted infection. And it is important to include monkeypox in our differential,” Dr. Jamieson said. “We are trying to get the word out that it needs to be part of what you think about when you see a patient with genital ulcers.”

Health care professionals have acquired monkeypox through contact with patients or fomites, so clinicians should be sure to use appropriate precautions when evaluating patients who might have monkeypox, Dr. Jamieson added. Appropriate protective measures include wearing a gown, gloves, eye protection, and an N95.

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

Richard Martinello, MD, a professor of medicine and pediatric infectious diseases at Yale University, New haven, Conn., doesn’t expect to see a child hospitalized with respiratory syncytial virus (RSV) in the middle of summer. The illness, which can strike infants and older adults especially hard, is known as a “winter virus.”

But not this year. Over the last several weeks, he says, admissions for children with RSV have increased at the Yale New Haven Children’s Hospital. While the numbers aren’t large, they are out of the ordinary, he says, “because usually, at this time of year, we see zero. For lack of a better term, it’s weird.”

Likewise, William Schaffner, MD, a professor of infectious diseases at Vanderbilt University in Nashville, says RSV is on the rise there. Tennessee is one of 10 states taking part in a Centers for Disease Control and Prevention surveillance system that tracks influenza, RSV, and COVID-19.

He says RSV cases have risen by at least a third during the past week, including all age ranges. At this time of year, he says, “We aren’t supposed to have any RSV.”

RSV isn’t the only virus thriving out of season or otherwise acting strangely. Since the pandemic began, flu seasons have been out of whack – sometimes nearly nonexistent and other times extending well beyond “normal” seasons. Some experts say one influenza “B” strain may now be extinct, while others say it will be back.

Severe colds – what some call “super colds” – also seem to be on the rise in recent warm-weather months, although that evidence is mostly based on personal experience, not science.

Trying to explain these out-of-season variations has sparked much discussion among epidemiologists and virologists, Dr. Schaffner says, with debates ongoing about whether human behavior and habits or the seasons play a bigger role in the transmission of viral illness.

On top of that, scientists are also looking at the interactions between the SARS-CoV-2 virus that causes COVID-19 and other viruses. When people get hit with COVID-19 and other viruses at the same time, does that make COVID-19 more severe, or less?

Research is conflicting.
 

Summer of 2022: A repeat of 2021?

RSV. Most children contract the virus by age 2, and while it’s generally mild, about 58,000 children under age 5 years are hospitalized each year. During the pandemic, RSV cases decreased from January to April 2020, the CDC reported, and then remained at “historically low levels”: less than 1% positive RSV results a week, for the next year.

But cases began rising in April 2021.

“Last year, we did have an unusual summer,” Dr. Schaffner says. After lockdown ended, to everyone’s surprise, RSV infections rose.

That increase triggered a CDC health advisory in June 2021, telling doctors and caregivers about the increase in “interseasonal” RSV cases across parts of the Southern United States, recommending broader testing for RSV in patients who had a respiratory illness but tested negative for COVID.

Because of the reduced circulation of RSV during the winter of 2020 to 2021, the CDC warned, older infants and toddlers might have a higher risk of RSV since they weren’t exposed to typical levels of RSV for the previous 15 months.

What about 2022? “At the moment,” Dr. Schaffner says, “it looks like we are having a repeat [of 2021].”

On Twitter, other pediatricians, including those from Maine and Texas, have reported an increase in RSV cases this summer.

Influenza. From October 2020 until May 2021, flu activity was lower than during any previous flu season since at least 1997, according to the CDC.

In late 2021, researchers suggested that one line of influenza known as B/Yamagata may have become extinct.

The 2021-2022 flu season has been mild, the CDC says, but it has come in two waves, with the second wave lingering longer than previous ones. While flu activity is decreasing, last week the CDC said doctors should be alert to flu infections throughout the summer.

Colds. In reports on colds that aren’t based on science, several doctors say they are seeing more colds than usual in the summer, and they’re more severe than usual. According to the CDC, common coronaviruses and respiratory adenoviruses have been increasing since early 2021, and rhinoviruses since June 2020.

Behavior vs. seasons

In explaining the spread of viral respiratory diseases, infectious disease doctors consider two things. “One is that temperature and humidity in the winter favors longer survival of some viruses, leading to longer periods of possible transmission,” says Dean Blumberg, MD, a professor of pediatrics and chief of pediatric infectious disease at University of California Davis Health.

“The other is differences in human behavior, with people spending more time outside in the summer, which results in more distancing and [less] virus concentration due to very large air volume,” he says, and vice versa in winter.

What about the “super colds?” COVID-19 lockdowns and social distancing greatly reduced people’s exposure to common viruses like those that cause colds, says Neil A. Mabbott, PhD, a professor of immunopathology at the University of Edinburgh (Scotland).

“Immunity to these common cold viruses gained through natural infection is considered to last around 8 or 9 months or so,” he says. “Each winter, when we are exposed to the new circulating variants of these viruses, our immunity receives a natural boost.”

That explains why most people get a cold that’s relatively mild. But with all the pandemic lockdowns and the use of hand sanitizers, most people had limited exposure to other viruses, including the common cold. When people emerged from lockdown, the common cold viruses were beginning to circulate again.

“Our immune systems were less able to clear the infection than previously,” Dr. Mabbott says. “As a consequence, some may have experienced increased symptoms, giving the impression of being infected with a ‘super cold.’ ”

“The colds themselves are probably not different to those we got prepandemic,” says Ian Mackay, PhD, a virologist at the University of Queensland, Brisbane, Australia. “But there might be more of them. So I doubt they are ‘super colds’ as much as they are ‘super-perfect circumstances.’ ”

The colds themselves are probably not different to those we got prepandemic. But there might be more of them.

Those super-perfect circumstances, he says, include people gathering after lockdown; a lack of immunity in new babies; viruses that have remained, even if at low levels, but continue to mutate; and our waning immunity to the range of viruses we’d normally encounter.

While lack of exposure may partly explain why some viruses become rampant out of season, it’s likely not the only reason. For example, the reduced circulation of RSV in the population as a whole also may have reduced the transfer of immunity from mothers to infants, some researchers say, making those infants more vulnerable than usual.
 

Interactions of viruses

Another thing that may be driving the different behavior of viruses is that the SARS-CoV-2 virus could somehow be interacting with other respiratory viruses, Dr. Schaffner says. “And if so, what sort of interactions?”

Many researchers are looking into that, and how coinfections with other respiratory diseases, including the common cold and flu, may affect the course of COVID-19. Some studies have found that the T cells – a source of deeper, cellular immunity in people – generated after a common cold “may also provide cross-protection in some people against COVID-19.”

But another study found immunity against common cold–causing coronaviruses might make COVID-19 more severe.

When researchers in the United Kingdom studied nearly 7,000 patients infected with COVID-19, including 583 also infected with RSV, flu, or adenoviruses (causing flulike or coldlike illness), those with flu or adenovirus, compared with the others, were at higher risk of death.
 

To be continued …

Exactly how COVID-19 will be changing what we know of other viruses is yet to be determined, too.

Even before the pandemic, Dr. Martinello says, there were already some shifts in RSV. Florida, for instance, has an RSV season longer than the rest of the country, mimicking the pattern in the tropics.

Will the atypical patterns continue? “My guess is that this will settle out,” he says, with some sort of pattern developing. At this point, there are many unknowns. “We still can’t answer whether there will be some seasonality to COVID.”

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

Richard Martinello, MD, a professor of medicine and pediatric infectious diseases at Yale University, New haven, Conn., doesn’t expect to see a child hospitalized with respiratory syncytial virus (RSV) in the middle of summer. The illness, which can strike infants and older adults especially hard, is known as a “winter virus.”

But not this year. Over the last several weeks, he says, admissions for children with RSV have increased at the Yale New Haven Children’s Hospital. While the numbers aren’t large, they are out of the ordinary, he says, “because usually, at this time of year, we see zero. For lack of a better term, it’s weird.”

Likewise, William Schaffner, MD, a professor of infectious diseases at Vanderbilt University in Nashville, says RSV is on the rise there. Tennessee is one of 10 states taking part in a Centers for Disease Control and Prevention surveillance system that tracks influenza, RSV, and COVID-19.

He says RSV cases have risen by at least a third during the past week, including all age ranges. At this time of year, he says, “We aren’t supposed to have any RSV.”

RSV isn’t the only virus thriving out of season or otherwise acting strangely. Since the pandemic began, flu seasons have been out of whack – sometimes nearly nonexistent and other times extending well beyond “normal” seasons. Some experts say one influenza “B” strain may now be extinct, while others say it will be back.

Severe colds – what some call “super colds” – also seem to be on the rise in recent warm-weather months, although that evidence is mostly based on personal experience, not science.

Trying to explain these out-of-season variations has sparked much discussion among epidemiologists and virologists, Dr. Schaffner says, with debates ongoing about whether human behavior and habits or the seasons play a bigger role in the transmission of viral illness.

On top of that, scientists are also looking at the interactions between the SARS-CoV-2 virus that causes COVID-19 and other viruses. When people get hit with COVID-19 and other viruses at the same time, does that make COVID-19 more severe, or less?

Research is conflicting.
 

Summer of 2022: A repeat of 2021?

RSV. Most children contract the virus by age 2, and while it’s generally mild, about 58,000 children under age 5 years are hospitalized each year. During the pandemic, RSV cases decreased from January to April 2020, the CDC reported, and then remained at “historically low levels”: less than 1% positive RSV results a week, for the next year.

But cases began rising in April 2021.

“Last year, we did have an unusual summer,” Dr. Schaffner says. After lockdown ended, to everyone’s surprise, RSV infections rose.

That increase triggered a CDC health advisory in June 2021, telling doctors and caregivers about the increase in “interseasonal” RSV cases across parts of the Southern United States, recommending broader testing for RSV in patients who had a respiratory illness but tested negative for COVID.

Because of the reduced circulation of RSV during the winter of 2020 to 2021, the CDC warned, older infants and toddlers might have a higher risk of RSV since they weren’t exposed to typical levels of RSV for the previous 15 months.

What about 2022? “At the moment,” Dr. Schaffner says, “it looks like we are having a repeat [of 2021].”

On Twitter, other pediatricians, including those from Maine and Texas, have reported an increase in RSV cases this summer.

Influenza. From October 2020 until May 2021, flu activity was lower than during any previous flu season since at least 1997, according to the CDC.

In late 2021, researchers suggested that one line of influenza known as B/Yamagata may have become extinct.

The 2021-2022 flu season has been mild, the CDC says, but it has come in two waves, with the second wave lingering longer than previous ones. While flu activity is decreasing, last week the CDC said doctors should be alert to flu infections throughout the summer.

Colds. In reports on colds that aren’t based on science, several doctors say they are seeing more colds than usual in the summer, and they’re more severe than usual. According to the CDC, common coronaviruses and respiratory adenoviruses have been increasing since early 2021, and rhinoviruses since June 2020.

Behavior vs. seasons

In explaining the spread of viral respiratory diseases, infectious disease doctors consider two things. “One is that temperature and humidity in the winter favors longer survival of some viruses, leading to longer periods of possible transmission,” says Dean Blumberg, MD, a professor of pediatrics and chief of pediatric infectious disease at University of California Davis Health.

“The other is differences in human behavior, with people spending more time outside in the summer, which results in more distancing and [less] virus concentration due to very large air volume,” he says, and vice versa in winter.

What about the “super colds?” COVID-19 lockdowns and social distancing greatly reduced people’s exposure to common viruses like those that cause colds, says Neil A. Mabbott, PhD, a professor of immunopathology at the University of Edinburgh (Scotland).

“Immunity to these common cold viruses gained through natural infection is considered to last around 8 or 9 months or so,” he says. “Each winter, when we are exposed to the new circulating variants of these viruses, our immunity receives a natural boost.”

That explains why most people get a cold that’s relatively mild. But with all the pandemic lockdowns and the use of hand sanitizers, most people had limited exposure to other viruses, including the common cold. When people emerged from lockdown, the common cold viruses were beginning to circulate again.

“Our immune systems were less able to clear the infection than previously,” Dr. Mabbott says. “As a consequence, some may have experienced increased symptoms, giving the impression of being infected with a ‘super cold.’ ”

“The colds themselves are probably not different to those we got prepandemic,” says Ian Mackay, PhD, a virologist at the University of Queensland, Brisbane, Australia. “But there might be more of them. So I doubt they are ‘super colds’ as much as they are ‘super-perfect circumstances.’ ”

The colds themselves are probably not different to those we got prepandemic. But there might be more of them.

Those super-perfect circumstances, he says, include people gathering after lockdown; a lack of immunity in new babies; viruses that have remained, even if at low levels, but continue to mutate; and our waning immunity to the range of viruses we’d normally encounter.

While lack of exposure may partly explain why some viruses become rampant out of season, it’s likely not the only reason. For example, the reduced circulation of RSV in the population as a whole also may have reduced the transfer of immunity from mothers to infants, some researchers say, making those infants more vulnerable than usual.
 

Interactions of viruses

Another thing that may be driving the different behavior of viruses is that the SARS-CoV-2 virus could somehow be interacting with other respiratory viruses, Dr. Schaffner says. “And if so, what sort of interactions?”

Many researchers are looking into that, and how coinfections with other respiratory diseases, including the common cold and flu, may affect the course of COVID-19. Some studies have found that the T cells – a source of deeper, cellular immunity in people – generated after a common cold “may also provide cross-protection in some people against COVID-19.”

But another study found immunity against common cold–causing coronaviruses might make COVID-19 more severe.

When researchers in the United Kingdom studied nearly 7,000 patients infected with COVID-19, including 583 also infected with RSV, flu, or adenoviruses (causing flulike or coldlike illness), those with flu or adenovirus, compared with the others, were at higher risk of death.
 

To be continued …

Exactly how COVID-19 will be changing what we know of other viruses is yet to be determined, too.

Even before the pandemic, Dr. Martinello says, there were already some shifts in RSV. Florida, for instance, has an RSV season longer than the rest of the country, mimicking the pattern in the tropics.

Will the atypical patterns continue? “My guess is that this will settle out,” he says, with some sort of pattern developing. At this point, there are many unknowns. “We still can’t answer whether there will be some seasonality to COVID.”

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

Richard Martinello, MD, a professor of medicine and pediatric infectious diseases at Yale University, New haven, Conn., doesn’t expect to see a child hospitalized with respiratory syncytial virus (RSV) in the middle of summer. The illness, which can strike infants and older adults especially hard, is known as a “winter virus.”

But not this year. Over the last several weeks, he says, admissions for children with RSV have increased at the Yale New Haven Children’s Hospital. While the numbers aren’t large, they are out of the ordinary, he says, “because usually, at this time of year, we see zero. For lack of a better term, it’s weird.”

Likewise, William Schaffner, MD, a professor of infectious diseases at Vanderbilt University in Nashville, says RSV is on the rise there. Tennessee is one of 10 states taking part in a Centers for Disease Control and Prevention surveillance system that tracks influenza, RSV, and COVID-19.

He says RSV cases have risen by at least a third during the past week, including all age ranges. At this time of year, he says, “We aren’t supposed to have any RSV.”

RSV isn’t the only virus thriving out of season or otherwise acting strangely. Since the pandemic began, flu seasons have been out of whack – sometimes nearly nonexistent and other times extending well beyond “normal” seasons. Some experts say one influenza “B” strain may now be extinct, while others say it will be back.

Severe colds – what some call “super colds” – also seem to be on the rise in recent warm-weather months, although that evidence is mostly based on personal experience, not science.

Trying to explain these out-of-season variations has sparked much discussion among epidemiologists and virologists, Dr. Schaffner says, with debates ongoing about whether human behavior and habits or the seasons play a bigger role in the transmission of viral illness.

On top of that, scientists are also looking at the interactions between the SARS-CoV-2 virus that causes COVID-19 and other viruses. When people get hit with COVID-19 and other viruses at the same time, does that make COVID-19 more severe, or less?

Research is conflicting.
 

Summer of 2022: A repeat of 2021?

RSV. Most children contract the virus by age 2, and while it’s generally mild, about 58,000 children under age 5 years are hospitalized each year. During the pandemic, RSV cases decreased from January to April 2020, the CDC reported, and then remained at “historically low levels”: less than 1% positive RSV results a week, for the next year.

But cases began rising in April 2021.

“Last year, we did have an unusual summer,” Dr. Schaffner says. After lockdown ended, to everyone’s surprise, RSV infections rose.

That increase triggered a CDC health advisory in June 2021, telling doctors and caregivers about the increase in “interseasonal” RSV cases across parts of the Southern United States, recommending broader testing for RSV in patients who had a respiratory illness but tested negative for COVID.

Because of the reduced circulation of RSV during the winter of 2020 to 2021, the CDC warned, older infants and toddlers might have a higher risk of RSV since they weren’t exposed to typical levels of RSV for the previous 15 months.

What about 2022? “At the moment,” Dr. Schaffner says, “it looks like we are having a repeat [of 2021].”

On Twitter, other pediatricians, including those from Maine and Texas, have reported an increase in RSV cases this summer.

Influenza. From October 2020 until May 2021, flu activity was lower than during any previous flu season since at least 1997, according to the CDC.

In late 2021, researchers suggested that one line of influenza known as B/Yamagata may have become extinct.

The 2021-2022 flu season has been mild, the CDC says, but it has come in two waves, with the second wave lingering longer than previous ones. While flu activity is decreasing, last week the CDC said doctors should be alert to flu infections throughout the summer.

Colds. In reports on colds that aren’t based on science, several doctors say they are seeing more colds than usual in the summer, and they’re more severe than usual. According to the CDC, common coronaviruses and respiratory adenoviruses have been increasing since early 2021, and rhinoviruses since June 2020.

Behavior vs. seasons

In explaining the spread of viral respiratory diseases, infectious disease doctors consider two things. “One is that temperature and humidity in the winter favors longer survival of some viruses, leading to longer periods of possible transmission,” says Dean Blumberg, MD, a professor of pediatrics and chief of pediatric infectious disease at University of California Davis Health.

“The other is differences in human behavior, with people spending more time outside in the summer, which results in more distancing and [less] virus concentration due to very large air volume,” he says, and vice versa in winter.

What about the “super colds?” COVID-19 lockdowns and social distancing greatly reduced people’s exposure to common viruses like those that cause colds, says Neil A. Mabbott, PhD, a professor of immunopathology at the University of Edinburgh (Scotland).

“Immunity to these common cold viruses gained through natural infection is considered to last around 8 or 9 months or so,” he says. “Each winter, when we are exposed to the new circulating variants of these viruses, our immunity receives a natural boost.”

That explains why most people get a cold that’s relatively mild. But with all the pandemic lockdowns and the use of hand sanitizers, most people had limited exposure to other viruses, including the common cold. When people emerged from lockdown, the common cold viruses were beginning to circulate again.

“Our immune systems were less able to clear the infection than previously,” Dr. Mabbott says. “As a consequence, some may have experienced increased symptoms, giving the impression of being infected with a ‘super cold.’ ”

“The colds themselves are probably not different to those we got prepandemic,” says Ian Mackay, PhD, a virologist at the University of Queensland, Brisbane, Australia. “But there might be more of them. So I doubt they are ‘super colds’ as much as they are ‘super-perfect circumstances.’ ”

The colds themselves are probably not different to those we got prepandemic. But there might be more of them.

Those super-perfect circumstances, he says, include people gathering after lockdown; a lack of immunity in new babies; viruses that have remained, even if at low levels, but continue to mutate; and our waning immunity to the range of viruses we’d normally encounter.

While lack of exposure may partly explain why some viruses become rampant out of season, it’s likely not the only reason. For example, the reduced circulation of RSV in the population as a whole also may have reduced the transfer of immunity from mothers to infants, some researchers say, making those infants more vulnerable than usual.
 

Interactions of viruses

Another thing that may be driving the different behavior of viruses is that the SARS-CoV-2 virus could somehow be interacting with other respiratory viruses, Dr. Schaffner says. “And if so, what sort of interactions?”

Many researchers are looking into that, and how coinfections with other respiratory diseases, including the common cold and flu, may affect the course of COVID-19. Some studies have found that the T cells – a source of deeper, cellular immunity in people – generated after a common cold “may also provide cross-protection in some people against COVID-19.”

But another study found immunity against common cold–causing coronaviruses might make COVID-19 more severe.

When researchers in the United Kingdom studied nearly 7,000 patients infected with COVID-19, including 583 also infected with RSV, flu, or adenoviruses (causing flulike or coldlike illness), those with flu or adenovirus, compared with the others, were at higher risk of death.
 

To be continued …

Exactly how COVID-19 will be changing what we know of other viruses is yet to be determined, too.

Even before the pandemic, Dr. Martinello says, there were already some shifts in RSV. Florida, for instance, has an RSV season longer than the rest of the country, mimicking the pattern in the tropics.

Will the atypical patterns continue? “My guess is that this will settle out,” he says, with some sort of pattern developing. At this point, there are many unknowns. “We still can’t answer whether there will be some seasonality to COVID.”

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

MONTREAL – Long-acting, injectable cabotegravir (CAB LA) continues to show superiority over oral daily tenofovir diphosphate plus emtricitabine (TDF-FTC) as preexposure prophylaxis (PrEP) for HIV, according to new data from two HIV Prevention Trials Network (HPTN) studies reported at the International AIDS Society Conference.

Follow-up data from the HPTN 084 trial, which compared the two regimens in 3,224 sub-Saharan persons who were assigned female sex at birth, show that three new HIV infections occurred in the CAB LA group in the 12 months since the study was unblinded, versus 20 new infections among the TDF-FTC group. That translates to an 89% lower risk of infection in the CAB LA arm across both the blinded and unblinded phases of the trial, said lead investigator Sinead Delany-Moretlwe, MD, PhD, director of research, Wits Reproductive Health and HIV Institute, the University of the Witwatersrand, Johannesburg, South Africa, during a press conference.

“The trial was designed with the assumption that both drugs were highly effective in preventing HIV infection but that, given the challenges with taking a pill a day, that injectable cabotegravir may offer an adherence advantage,” she said in an interview. “Our data appear to confirm this, as most of the participants in the TDF-FTC arm who became infected with HIV had evidence of poor or inconsistent use of PrEP.”

The study also found that pregnancy incidence increased “two- to threefold” between the blinded and the unblinded period, “and this emphasizes to us the desire of women to conceive safely, without the threat of HIV, and the importance of us continuing to evaluate the safety and pharmacology of cabotegravir in pregnant and breastfeeding women during open-label extension phase of HPTN 084, so that [they] are not excluded from access to this highly effective PrEP agent,” she said. To date, no congenital anomalies have been reported in babies born during the study.

In an update report from HPTN 083, which also showed superiority of CAB LA over TDF-FTC in cisgender men and transgender women (TGW), researchers reported the safety and efficacy of CAB LA use in TGW using gender-affirming hormone therapy (GAHT).

Among the 4,566 participants in HPTN 083, 570 were TGW, and of those, 58% used GAHT at baseline, reported Beatriz Grinsztejn, MD, PhD, head of the STD/AIDS Clinical Research Laboratory at the Instituto Nacional de Infectologicia/Fundação Oswaldo Cruz.

CAB LA drug concentrations measured in a subset of 53 TGW who received on-time CAB injections were comparable between those taking (n = 30) and those not taking GAHT (n = 23), “suggesting the lack of a gender-affirming hormone effect on CAB pharmacokinetics,” she said. “These are very promising results, as we all know that the use of gender-affirming hormone therapy is a major priority for our transgender women community, ... so the lack of drug-drug interaction is really a very important result.”

“Cabotegravir long-acting PrEP is now approved for all at-risk populations, including men who have sex with men, transgender women, and cisgender women, after the results of HPTN 083 and 084,” commented Monica Gandhi, MD, MPH, an infectious disease physician, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco (UCSF).

Dr. Gandhi, who was not involved in either study, is also director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “The incredible efficacy of long-acting PrEP for cisgender women shown by HPTN 084 is game-changing for our practice, and we have already instituted CAB LA across a range of populations at Ward 86,” she said in an interview. “The durability of the 89% additional efficacy of CAB LA over oral TDF/FTC is thrilling and will lead to a greater use of long-acting options.”

She acknowledged that information on potential interactions of GAHT was needed from the HPTN 083 trial. “That cabotegravir levels did not change with the use of estradiol or spironolactone for gender-affirming therapy is important news for our practice and to reassure our TGW that they can safely and effectively use CAB LA for HIV prevention.”

The HPTN 084 and 083 trials were funded by the National Institutes for Allergy and Infectious Diseases. Dr. Delany-Moretlwe, Dr. Grinsztejn, and Dr. Gandhi have disclosed no relevant financial relationships.

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

MONTREAL – Long-acting, injectable cabotegravir (CAB LA) continues to show superiority over oral daily tenofovir diphosphate plus emtricitabine (TDF-FTC) as preexposure prophylaxis (PrEP) for HIV, according to new data from two HIV Prevention Trials Network (HPTN) studies reported at the International AIDS Society Conference.

Follow-up data from the HPTN 084 trial, which compared the two regimens in 3,224 sub-Saharan persons who were assigned female sex at birth, show that three new HIV infections occurred in the CAB LA group in the 12 months since the study was unblinded, versus 20 new infections among the TDF-FTC group. That translates to an 89% lower risk of infection in the CAB LA arm across both the blinded and unblinded phases of the trial, said lead investigator Sinead Delany-Moretlwe, MD, PhD, director of research, Wits Reproductive Health and HIV Institute, the University of the Witwatersrand, Johannesburg, South Africa, during a press conference.

“The trial was designed with the assumption that both drugs were highly effective in preventing HIV infection but that, given the challenges with taking a pill a day, that injectable cabotegravir may offer an adherence advantage,” she said in an interview. “Our data appear to confirm this, as most of the participants in the TDF-FTC arm who became infected with HIV had evidence of poor or inconsistent use of PrEP.”

The study also found that pregnancy incidence increased “two- to threefold” between the blinded and the unblinded period, “and this emphasizes to us the desire of women to conceive safely, without the threat of HIV, and the importance of us continuing to evaluate the safety and pharmacology of cabotegravir in pregnant and breastfeeding women during open-label extension phase of HPTN 084, so that [they] are not excluded from access to this highly effective PrEP agent,” she said. To date, no congenital anomalies have been reported in babies born during the study.

In an update report from HPTN 083, which also showed superiority of CAB LA over TDF-FTC in cisgender men and transgender women (TGW), researchers reported the safety and efficacy of CAB LA use in TGW using gender-affirming hormone therapy (GAHT).

Among the 4,566 participants in HPTN 083, 570 were TGW, and of those, 58% used GAHT at baseline, reported Beatriz Grinsztejn, MD, PhD, head of the STD/AIDS Clinical Research Laboratory at the Instituto Nacional de Infectologicia/Fundação Oswaldo Cruz.

CAB LA drug concentrations measured in a subset of 53 TGW who received on-time CAB injections were comparable between those taking (n = 30) and those not taking GAHT (n = 23), “suggesting the lack of a gender-affirming hormone effect on CAB pharmacokinetics,” she said. “These are very promising results, as we all know that the use of gender-affirming hormone therapy is a major priority for our transgender women community, ... so the lack of drug-drug interaction is really a very important result.”

“Cabotegravir long-acting PrEP is now approved for all at-risk populations, including men who have sex with men, transgender women, and cisgender women, after the results of HPTN 083 and 084,” commented Monica Gandhi, MD, MPH, an infectious disease physician, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco (UCSF).

Dr. Gandhi, who was not involved in either study, is also director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “The incredible efficacy of long-acting PrEP for cisgender women shown by HPTN 084 is game-changing for our practice, and we have already instituted CAB LA across a range of populations at Ward 86,” she said in an interview. “The durability of the 89% additional efficacy of CAB LA over oral TDF/FTC is thrilling and will lead to a greater use of long-acting options.”

She acknowledged that information on potential interactions of GAHT was needed from the HPTN 083 trial. “That cabotegravir levels did not change with the use of estradiol or spironolactone for gender-affirming therapy is important news for our practice and to reassure our TGW that they can safely and effectively use CAB LA for HIV prevention.”

The HPTN 084 and 083 trials were funded by the National Institutes for Allergy and Infectious Diseases. Dr. Delany-Moretlwe, Dr. Grinsztejn, and Dr. Gandhi have disclosed no relevant financial relationships.

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

MONTREAL – Long-acting, injectable cabotegravir (CAB LA) continues to show superiority over oral daily tenofovir diphosphate plus emtricitabine (TDF-FTC) as preexposure prophylaxis (PrEP) for HIV, according to new data from two HIV Prevention Trials Network (HPTN) studies reported at the International AIDS Society Conference.

Follow-up data from the HPTN 084 trial, which compared the two regimens in 3,224 sub-Saharan persons who were assigned female sex at birth, show that three new HIV infections occurred in the CAB LA group in the 12 months since the study was unblinded, versus 20 new infections among the TDF-FTC group. That translates to an 89% lower risk of infection in the CAB LA arm across both the blinded and unblinded phases of the trial, said lead investigator Sinead Delany-Moretlwe, MD, PhD, director of research, Wits Reproductive Health and HIV Institute, the University of the Witwatersrand, Johannesburg, South Africa, during a press conference.

“The trial was designed with the assumption that both drugs were highly effective in preventing HIV infection but that, given the challenges with taking a pill a day, that injectable cabotegravir may offer an adherence advantage,” she said in an interview. “Our data appear to confirm this, as most of the participants in the TDF-FTC arm who became infected with HIV had evidence of poor or inconsistent use of PrEP.”

The study also found that pregnancy incidence increased “two- to threefold” between the blinded and the unblinded period, “and this emphasizes to us the desire of women to conceive safely, without the threat of HIV, and the importance of us continuing to evaluate the safety and pharmacology of cabotegravir in pregnant and breastfeeding women during open-label extension phase of HPTN 084, so that [they] are not excluded from access to this highly effective PrEP agent,” she said. To date, no congenital anomalies have been reported in babies born during the study.

In an update report from HPTN 083, which also showed superiority of CAB LA over TDF-FTC in cisgender men and transgender women (TGW), researchers reported the safety and efficacy of CAB LA use in TGW using gender-affirming hormone therapy (GAHT).

Among the 4,566 participants in HPTN 083, 570 were TGW, and of those, 58% used GAHT at baseline, reported Beatriz Grinsztejn, MD, PhD, head of the STD/AIDS Clinical Research Laboratory at the Instituto Nacional de Infectologicia/Fundação Oswaldo Cruz.

CAB LA drug concentrations measured in a subset of 53 TGW who received on-time CAB injections were comparable between those taking (n = 30) and those not taking GAHT (n = 23), “suggesting the lack of a gender-affirming hormone effect on CAB pharmacokinetics,” she said. “These are very promising results, as we all know that the use of gender-affirming hormone therapy is a major priority for our transgender women community, ... so the lack of drug-drug interaction is really a very important result.”

“Cabotegravir long-acting PrEP is now approved for all at-risk populations, including men who have sex with men, transgender women, and cisgender women, after the results of HPTN 083 and 084,” commented Monica Gandhi, MD, MPH, an infectious disease physician, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco (UCSF).

Dr. Gandhi, who was not involved in either study, is also director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “The incredible efficacy of long-acting PrEP for cisgender women shown by HPTN 084 is game-changing for our practice, and we have already instituted CAB LA across a range of populations at Ward 86,” she said in an interview. “The durability of the 89% additional efficacy of CAB LA over oral TDF/FTC is thrilling and will lead to a greater use of long-acting options.”

She acknowledged that information on potential interactions of GAHT was needed from the HPTN 083 trial. “That cabotegravir levels did not change with the use of estradiol or spironolactone for gender-affirming therapy is important news for our practice and to reassure our TGW that they can safely and effectively use CAB LA for HIV prevention.”

The HPTN 084 and 083 trials were funded by the National Institutes for Allergy and Infectious Diseases. Dr. Delany-Moretlwe, Dr. Grinsztejn, and Dr. Gandhi have disclosed no relevant financial relationships.

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

New pediatric COVID-19 cases increased for the third straight week as a substantial number of children under age 5 years started to receive their second doses of the vaccine.

Despite the 3-week trend, however, there are some positive signs. The new-case count for the latest reporting week (July 22-28) was over 95,000, but the 3.9% increase over the previous week’s 92,000 cases is much smaller than that week’s (July 15-21) corresponding jump of almost 22% over the July 8-14 total (75,000), according to the American Academy of Pediatrics and the Children’s Hospital Association.

On the not-so-positive side is the trend in admissions among children aged 0-17 years, which continue to climb steadily and have nearly equaled the highest rate seen during the Delta surge in 2021. The rate on July 29 was 0.46 admissions per 100,000 population, and the highest rate over the course of the Delta surge was 0.47 per 100,000, but the all-time high from the Omicron surge – 1.25 per 100,000 in mid-January – is still a long way off, based on data from the Centers for Disease Control and Prevention.

A similar situation is occurring with emergency department visits, but there is differentiation by age group. Among those aged 0-11 years, visits with diagnosed COVID made up 6.5% of all their ED visits on July 25, which was well above the high (4.0%) during the Delta surge, the CDC said.

That is not the case, however, for the older children, for whom rates are rising more slowly. Those aged 12-15 have reached 3.4% so far this summer, as have the 16- to 17-years-olds, versus Delta highs last year of around 7%, the CDC said on its COVID Data Tracker. As with admissions, though, current rates are well below the all-time Omicron high points, the CDC data show.
 

Joining the ranks of the fully vaccinated

Over the last 2 weeks, the first children to receive the COVID vaccine after its approval for those under age 5 years have been coming back for their second doses. Almost 50,000, about 0.3% of all those in that age group, had done so by July 27. Just over 662,000, about 3.4% of the total under-5 population, have received at least one dose, the CDC said.

Meanwhile, analysis of “data from the first several weeks following availability of the vaccine in this age group indicate high variability across states,” the AAP said in its weekly vaccination report. In the District of Columbia, 20.7% of all children under age 5 have received an initial dose as of July 27, as have 15.5% of those in Vermont and 12.5% in Massachusetts. No other state was above 10%, but Mississippi, at 0.7%, was the only one below 1%.

The older children, obviously, have a head start, so their numbers are much higher. At the state level, Vermont has the highest initial dose rate, 69%, for those aged 5-11 years, while Alabama, Mississippi, and Wyoming, at 17%, are looking up at everyone else in the country. Among children aged 12-17 years, D.C. is the highest with 100% vaccination – Massachusetts and Rhode Island are at 98% – and Wyoming is the lowest with 40%, the AAP said.

[email protected]

New pediatric COVID-19 cases increased for the third straight week as a substantial number of children under age 5 years started to receive their second doses of the vaccine.

Despite the 3-week trend, however, there are some positive signs. The new-case count for the latest reporting week (July 22-28) was over 95,000, but the 3.9% increase over the previous week’s 92,000 cases is much smaller than that week’s (July 15-21) corresponding jump of almost 22% over the July 8-14 total (75,000), according to the American Academy of Pediatrics and the Children’s Hospital Association.

On the not-so-positive side is the trend in admissions among children aged 0-17 years, which continue to climb steadily and have nearly equaled the highest rate seen during the Delta surge in 2021. The rate on July 29 was 0.46 admissions per 100,000 population, and the highest rate over the course of the Delta surge was 0.47 per 100,000, but the all-time high from the Omicron surge – 1.25 per 100,000 in mid-January – is still a long way off, based on data from the Centers for Disease Control and Prevention.

A similar situation is occurring with emergency department visits, but there is differentiation by age group. Among those aged 0-11 years, visits with diagnosed COVID made up 6.5% of all their ED visits on July 25, which was well above the high (4.0%) during the Delta surge, the CDC said.

That is not the case, however, for the older children, for whom rates are rising more slowly. Those aged 12-15 have reached 3.4% so far this summer, as have the 16- to 17-years-olds, versus Delta highs last year of around 7%, the CDC said on its COVID Data Tracker. As with admissions, though, current rates are well below the all-time Omicron high points, the CDC data show.
 

Joining the ranks of the fully vaccinated

Over the last 2 weeks, the first children to receive the COVID vaccine after its approval for those under age 5 years have been coming back for their second doses. Almost 50,000, about 0.3% of all those in that age group, had done so by July 27. Just over 662,000, about 3.4% of the total under-5 population, have received at least one dose, the CDC said.

Meanwhile, analysis of “data from the first several weeks following availability of the vaccine in this age group indicate high variability across states,” the AAP said in its weekly vaccination report. In the District of Columbia, 20.7% of all children under age 5 have received an initial dose as of July 27, as have 15.5% of those in Vermont and 12.5% in Massachusetts. No other state was above 10%, but Mississippi, at 0.7%, was the only one below 1%.

The older children, obviously, have a head start, so their numbers are much higher. At the state level, Vermont has the highest initial dose rate, 69%, for those aged 5-11 years, while Alabama, Mississippi, and Wyoming, at 17%, are looking up at everyone else in the country. Among children aged 12-17 years, D.C. is the highest with 100% vaccination – Massachusetts and Rhode Island are at 98% – and Wyoming is the lowest with 40%, the AAP said.

[email protected]

New pediatric COVID-19 cases increased for the third straight week as a substantial number of children under age 5 years started to receive their second doses of the vaccine.

Despite the 3-week trend, however, there are some positive signs. The new-case count for the latest reporting week (July 22-28) was over 95,000, but the 3.9% increase over the previous week’s 92,000 cases is much smaller than that week’s (July 15-21) corresponding jump of almost 22% over the July 8-14 total (75,000), according to the American Academy of Pediatrics and the Children’s Hospital Association.

On the not-so-positive side is the trend in admissions among children aged 0-17 years, which continue to climb steadily and have nearly equaled the highest rate seen during the Delta surge in 2021. The rate on July 29 was 0.46 admissions per 100,000 population, and the highest rate over the course of the Delta surge was 0.47 per 100,000, but the all-time high from the Omicron surge – 1.25 per 100,000 in mid-January – is still a long way off, based on data from the Centers for Disease Control and Prevention.

A similar situation is occurring with emergency department visits, but there is differentiation by age group. Among those aged 0-11 years, visits with diagnosed COVID made up 6.5% of all their ED visits on July 25, which was well above the high (4.0%) during the Delta surge, the CDC said.

That is not the case, however, for the older children, for whom rates are rising more slowly. Those aged 12-15 have reached 3.4% so far this summer, as have the 16- to 17-years-olds, versus Delta highs last year of around 7%, the CDC said on its COVID Data Tracker. As with admissions, though, current rates are well below the all-time Omicron high points, the CDC data show.
 

Joining the ranks of the fully vaccinated

Over the last 2 weeks, the first children to receive the COVID vaccine after its approval for those under age 5 years have been coming back for their second doses. Almost 50,000, about 0.3% of all those in that age group, had done so by July 27. Just over 662,000, about 3.4% of the total under-5 population, have received at least one dose, the CDC said.

Meanwhile, analysis of “data from the first several weeks following availability of the vaccine in this age group indicate high variability across states,” the AAP said in its weekly vaccination report. In the District of Columbia, 20.7% of all children under age 5 have received an initial dose as of July 27, as have 15.5% of those in Vermont and 12.5% in Massachusetts. No other state was above 10%, but Mississippi, at 0.7%, was the only one below 1%.

The older children, obviously, have a head start, so their numbers are much higher. At the state level, Vermont has the highest initial dose rate, 69%, for those aged 5-11 years, while Alabama, Mississippi, and Wyoming, at 17%, are looking up at everyone else in the country. Among children aged 12-17 years, D.C. is the highest with 100% vaccination – Massachusetts and Rhode Island are at 98% – and Wyoming is the lowest with 40%, the AAP said.

[email protected]

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

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

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

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

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

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

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

MONTREAL – One 200-mg dose of doxycycline taken as postexposure prophylaxis (PEP) reduced the incidence of three sexually transmitted infections (STIs) by 65% among men who have sex with men (MSM) and transgender women (TGW) living with HIV or taking preexposure prophylaxis (PrEP). The results of the open-label DoxyPEP trial were reported at a press conference at a meeting of the International AIDS Society.

“It is time to take action on the data that we have and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way,” said co-principal investigator Annie Luetkemeyer, MD, of Zuckerberg San Francisco General Hospital, and professor of medicine at the University of California, San Francisco (UCSF).

The open-label trial, conducted in Seattle and San Francisco, randomized MSM/TGW living with HIV or on PrEP, and with a history of N. gonorrhoeae (GC), C. trachomatis (CT), or early syphilis in the past year, to either doxycycline or none within 72 hours of having condomless sex. It was stopped early in May when a planned interim analysis showed those randomized to take doxycycline had substantially fewer STIs than participants assigned to the control group.

The intent-to-treat analysis included 501 patients with at least one quarter of follow-up: 327 taking PrEP and 174 living with HIV. Among those taking PrEP, new STIs (GC, CT or syphilis) occurred in 31.9% of control participants vs. 10.7% of those taking doxycycline – a reduction of 66% per quarter (P < .001). Among participants living with HIV, new STIs occurred in 30.5% of controls vs. 11.8% taking doxycycline, for a 62% reduction in STIs per quarter (P < .0001).

“Participants reported taking doxycycline 87% of the time after having condomless sex, about half of participants took fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses of doxycycline per month,” said Dr. Luetkemeyer, adding that there were no serious – grade 2 or greater – adverse events, and “the majority of participants reported that taking doxy was acceptable or very acceptable.”

Asked how broadly doxycycline prophylaxis could be used in other populations, Dr. Luetkemeyer was cautious. “Our study participants had a very high rate of new STIs – a 30% incidence per quarter  and using doxyPEP was well tolerated and very effective to reduce new STIs. However, this is a fairly limited population,” she said. “Whether doxyPEP should be considered for other groups, such as women on PrEP or with an elevated risk for STIs, will need more data which will be forthcoming from ongoing studies.”  

Dr. Luetkemeyer said her group is looking at three possible risks of antibiotic resistance with the doxyPEP regimen: the risk to bystander bacteria such as Staphylococcus aureus or commensal neisseria; the impact on the gut; and the risk of resistance to antibiotic treatments for STI.

For the latter, “we don’t really think this is going to be an issue in chlamydia and syphilis, and we’re looking carefully at gonorrhea,” she said, adding that it will be challenging to get definitive data from this particular study because of its short follow-up.

“Available culture data from those who had gonorrhea infections during the study demonstrated a relatively low rate of tetracycline resistance, which is a proxy for doxycycline resistance, at 20%. ... However, larger studies and population-based surveillance of those taking doxycycline as PEP are needed to understand if doxycycline use could drive the element of tetracycline resistance in gonorrhea,” she said, emphasizing that doxycycline is not used to treat active gonorrhea infections.

Calling the doxyPEP regimen a  “game-changing strategy,” Sharon Lewin, AO, PhD, president-elect of the International AIDS Society, said many physicians are already prescribing it off label based on the IPERGAY study (N Engl J Med. 2015; 373:2237-46) “but there’s a clear need for more evidence to guide the use of this intervention.”

“This study has huge implications for clinical care,” said Monica Gandhi, MD, MPH, an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at UCSF. “Although the data on drug resistance is very important to evaluate, we should certainly consider at this point using doxycycline PEP within 72 hours of condomless sex for our patients for STI prevention,” she said in an interview.

“In our practice, we are very excited about the possibility of a simple one-pill postexposure prophylactic agent (doxycycline 200 mg) to reduce the risk of a number of STIs. We have used PEP for HIV infection for a number of years and are very familiar with the concept of preventing infections after an exposure,” said Dr. Gandhi, director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “We are planning to institute doxycycline as PEP at my clinic after the release of these findings and will follow the remainder of the study findings closely.”

The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington. Medications were provided by Mayne Pharmaceuticals, and lab support by Hologic & Cepheid.

Dr. Lewin has the following disclosures: investigator-initiated, industry-funded research for Gilead, Viiv, Merck; scientific advisory board (honoraria paid to her personally) for Gilead, Merck, Viiv, Esfam, Immunocore, Vaxxinity; collaborative research (nonfunded) for AbbVie, Genentech, BMS. Dr. Luetkemeyer and Dr. Gandhi reported no relevant financial relationships.

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

MONTREAL – One 200-mg dose of doxycycline taken as postexposure prophylaxis (PEP) reduced the incidence of three sexually transmitted infections (STIs) by 65% among men who have sex with men (MSM) and transgender women (TGW) living with HIV or taking preexposure prophylaxis (PrEP). The results of the open-label DoxyPEP trial were reported at a press conference at a meeting of the International AIDS Society.

“It is time to take action on the data that we have and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way,” said co-principal investigator Annie Luetkemeyer, MD, of Zuckerberg San Francisco General Hospital, and professor of medicine at the University of California, San Francisco (UCSF).

The open-label trial, conducted in Seattle and San Francisco, randomized MSM/TGW living with HIV or on PrEP, and with a history of N. gonorrhoeae (GC), C. trachomatis (CT), or early syphilis in the past year, to either doxycycline or none within 72 hours of having condomless sex. It was stopped early in May when a planned interim analysis showed those randomized to take doxycycline had substantially fewer STIs than participants assigned to the control group.

The intent-to-treat analysis included 501 patients with at least one quarter of follow-up: 327 taking PrEP and 174 living with HIV. Among those taking PrEP, new STIs (GC, CT or syphilis) occurred in 31.9% of control participants vs. 10.7% of those taking doxycycline – a reduction of 66% per quarter (P < .001). Among participants living with HIV, new STIs occurred in 30.5% of controls vs. 11.8% taking doxycycline, for a 62% reduction in STIs per quarter (P < .0001).

“Participants reported taking doxycycline 87% of the time after having condomless sex, about half of participants took fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses of doxycycline per month,” said Dr. Luetkemeyer, adding that there were no serious – grade 2 or greater – adverse events, and “the majority of participants reported that taking doxy was acceptable or very acceptable.”

Asked how broadly doxycycline prophylaxis could be used in other populations, Dr. Luetkemeyer was cautious. “Our study participants had a very high rate of new STIs – a 30% incidence per quarter  and using doxyPEP was well tolerated and very effective to reduce new STIs. However, this is a fairly limited population,” she said. “Whether doxyPEP should be considered for other groups, such as women on PrEP or with an elevated risk for STIs, will need more data which will be forthcoming from ongoing studies.”  

Dr. Luetkemeyer said her group is looking at three possible risks of antibiotic resistance with the doxyPEP regimen: the risk to bystander bacteria such as Staphylococcus aureus or commensal neisseria; the impact on the gut; and the risk of resistance to antibiotic treatments for STI.

For the latter, “we don’t really think this is going to be an issue in chlamydia and syphilis, and we’re looking carefully at gonorrhea,” she said, adding that it will be challenging to get definitive data from this particular study because of its short follow-up.

“Available culture data from those who had gonorrhea infections during the study demonstrated a relatively low rate of tetracycline resistance, which is a proxy for doxycycline resistance, at 20%. ... However, larger studies and population-based surveillance of those taking doxycycline as PEP are needed to understand if doxycycline use could drive the element of tetracycline resistance in gonorrhea,” she said, emphasizing that doxycycline is not used to treat active gonorrhea infections.

Calling the doxyPEP regimen a  “game-changing strategy,” Sharon Lewin, AO, PhD, president-elect of the International AIDS Society, said many physicians are already prescribing it off label based on the IPERGAY study (N Engl J Med. 2015; 373:2237-46) “but there’s a clear need for more evidence to guide the use of this intervention.”

“This study has huge implications for clinical care,” said Monica Gandhi, MD, MPH, an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at UCSF. “Although the data on drug resistance is very important to evaluate, we should certainly consider at this point using doxycycline PEP within 72 hours of condomless sex for our patients for STI prevention,” she said in an interview.

“In our practice, we are very excited about the possibility of a simple one-pill postexposure prophylactic agent (doxycycline 200 mg) to reduce the risk of a number of STIs. We have used PEP for HIV infection for a number of years and are very familiar with the concept of preventing infections after an exposure,” said Dr. Gandhi, director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “We are planning to institute doxycycline as PEP at my clinic after the release of these findings and will follow the remainder of the study findings closely.”

The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington. Medications were provided by Mayne Pharmaceuticals, and lab support by Hologic & Cepheid.

Dr. Lewin has the following disclosures: investigator-initiated, industry-funded research for Gilead, Viiv, Merck; scientific advisory board (honoraria paid to her personally) for Gilead, Merck, Viiv, Esfam, Immunocore, Vaxxinity; collaborative research (nonfunded) for AbbVie, Genentech, BMS. Dr. Luetkemeyer and Dr. Gandhi reported no relevant financial relationships.

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

MONTREAL – One 200-mg dose of doxycycline taken as postexposure prophylaxis (PEP) reduced the incidence of three sexually transmitted infections (STIs) by 65% among men who have sex with men (MSM) and transgender women (TGW) living with HIV or taking preexposure prophylaxis (PrEP). The results of the open-label DoxyPEP trial were reported at a press conference at a meeting of the International AIDS Society.

“It is time to take action on the data that we have and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way,” said co-principal investigator Annie Luetkemeyer, MD, of Zuckerberg San Francisco General Hospital, and professor of medicine at the University of California, San Francisco (UCSF).

The open-label trial, conducted in Seattle and San Francisco, randomized MSM/TGW living with HIV or on PrEP, and with a history of N. gonorrhoeae (GC), C. trachomatis (CT), or early syphilis in the past year, to either doxycycline or none within 72 hours of having condomless sex. It was stopped early in May when a planned interim analysis showed those randomized to take doxycycline had substantially fewer STIs than participants assigned to the control group.

The intent-to-treat analysis included 501 patients with at least one quarter of follow-up: 327 taking PrEP and 174 living with HIV. Among those taking PrEP, new STIs (GC, CT or syphilis) occurred in 31.9% of control participants vs. 10.7% of those taking doxycycline – a reduction of 66% per quarter (P < .001). Among participants living with HIV, new STIs occurred in 30.5% of controls vs. 11.8% taking doxycycline, for a 62% reduction in STIs per quarter (P < .0001).

“Participants reported taking doxycycline 87% of the time after having condomless sex, about half of participants took fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses of doxycycline per month,” said Dr. Luetkemeyer, adding that there were no serious – grade 2 or greater – adverse events, and “the majority of participants reported that taking doxy was acceptable or very acceptable.”

Asked how broadly doxycycline prophylaxis could be used in other populations, Dr. Luetkemeyer was cautious. “Our study participants had a very high rate of new STIs – a 30% incidence per quarter  and using doxyPEP was well tolerated and very effective to reduce new STIs. However, this is a fairly limited population,” she said. “Whether doxyPEP should be considered for other groups, such as women on PrEP or with an elevated risk for STIs, will need more data which will be forthcoming from ongoing studies.”  

Dr. Luetkemeyer said her group is looking at three possible risks of antibiotic resistance with the doxyPEP regimen: the risk to bystander bacteria such as Staphylococcus aureus or commensal neisseria; the impact on the gut; and the risk of resistance to antibiotic treatments for STI.

For the latter, “we don’t really think this is going to be an issue in chlamydia and syphilis, and we’re looking carefully at gonorrhea,” she said, adding that it will be challenging to get definitive data from this particular study because of its short follow-up.

“Available culture data from those who had gonorrhea infections during the study demonstrated a relatively low rate of tetracycline resistance, which is a proxy for doxycycline resistance, at 20%. ... However, larger studies and population-based surveillance of those taking doxycycline as PEP are needed to understand if doxycycline use could drive the element of tetracycline resistance in gonorrhea,” she said, emphasizing that doxycycline is not used to treat active gonorrhea infections.

Calling the doxyPEP regimen a  “game-changing strategy,” Sharon Lewin, AO, PhD, president-elect of the International AIDS Society, said many physicians are already prescribing it off label based on the IPERGAY study (N Engl J Med. 2015; 373:2237-46) “but there’s a clear need for more evidence to guide the use of this intervention.”

“This study has huge implications for clinical care,” said Monica Gandhi, MD, MPH, an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at UCSF. “Although the data on drug resistance is very important to evaluate, we should certainly consider at this point using doxycycline PEP within 72 hours of condomless sex for our patients for STI prevention,” she said in an interview.

“In our practice, we are very excited about the possibility of a simple one-pill postexposure prophylactic agent (doxycycline 200 mg) to reduce the risk of a number of STIs. We have used PEP for HIV infection for a number of years and are very familiar with the concept of preventing infections after an exposure,” said Dr. Gandhi, director of the UCSF Center for AIDS Research and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “We are planning to institute doxycycline as PEP at my clinic after the release of these findings and will follow the remainder of the study findings closely.”

The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington. Medications were provided by Mayne Pharmaceuticals, and lab support by Hologic & Cepheid.

Dr. Lewin has the following disclosures: investigator-initiated, industry-funded research for Gilead, Viiv, Merck; scientific advisory board (honoraria paid to her personally) for Gilead, Merck, Viiv, Esfam, Immunocore, Vaxxinity; collaborative research (nonfunded) for AbbVie, Genentech, BMS. Dr. Luetkemeyer and Dr. Gandhi reported no relevant financial relationships.

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

More than 780,000 doses of the JYNNEOS monkeypox vaccine will be available in the United States beginning July 29, the Department of Health & Human Services announced on July 28 in a press call.

HHS Secretary Xavier Becerra urged local and state public health departments to use these doses for preventive vaccination efforts to stay ahead of the virus and end the outbreak, noting that the HHS and Centers for Disease Control and Prevention do not control how vaccines are distributed at state and local levels. “We don’t have the authority to tell them what to do,” he said during the call. “We need them to work with us.”

As of July 28, there were 4,907 reported cases of monkeypox in the United States and officials expect cases will continue to rise in the coming weeks.

HHS already has distributed more 338,000 doses to states and jurisdictions, but the vaccine remains in high demand. The vaccine is manufactured by the small Danish company Bavarian Nordic. These additional 786,000 doses were previously stored at a plant in Denmark, awaiting the completion of an inspection and authorization of the vaccine plant by the Food and Drug Administration. The agency announced on July 27 that both the vaccine doses and the manufacturing plant met standards.

With the announcement of these additional doses, the vaccine allocation plan is also being updated to take into account two important factors: the number of people at high risk in a jurisdiction and the number of new cases reported since the last vaccine allocation.

“This update gives greater weight to prioritizing vaccines to areas with the greatest number of people at risk, which includes men who have sex with men who have HIV or who are eligible for HIV pre-exposure prophylaxis, while still considering where we are seeing cases increase,” said Capt. Jennifer McQuiston, DVM, deputy director of the division of high consequence pathogens and pathology at the CDC.

Capt.McQuiston also provided additional demographic information on the U.S. outbreak. The median age of people with confirmed cases is 35 years old, with a range from 17 to 76. (This does not include the two cases in children reported on July 22.) Of the cases where sex at birth was provided, 99% were individuals assigned male sex at birth. In cases with reported ethnicity and race, 37% were non-Hispanic White people, 31% were Hispanic/Latino, 27% were Black or African American, and 4% were of Asian descent. The most common symptoms were rash – present in 99% of cases – malaise, fever, and swollen lymph nodes.

HHS and CDC did not have data on how many people have received at least one dose of the monkeypox vaccine. When asked how many people need to be fully vaccinated against monkeypox to contain the outbreak, Mr. Becerra did not provide an estimate but implied that preventive vaccination could help limit the number of vaccines needed and expressed optimism about quelling the outbreak in the United States. “We believe that we have done everything we can at the federal level to work with our state and local partners and communities affected to make sure we can stay ahead of this and end this outbreak,” he said, “but everybody’s got to do their part.”

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

More than 780,000 doses of the JYNNEOS monkeypox vaccine will be available in the United States beginning July 29, the Department of Health & Human Services announced on July 28 in a press call.

HHS Secretary Xavier Becerra urged local and state public health departments to use these doses for preventive vaccination efforts to stay ahead of the virus and end the outbreak, noting that the HHS and Centers for Disease Control and Prevention do not control how vaccines are distributed at state and local levels. “We don’t have the authority to tell them what to do,” he said during the call. “We need them to work with us.”

As of July 28, there were 4,907 reported cases of monkeypox in the United States and officials expect cases will continue to rise in the coming weeks.

HHS already has distributed more 338,000 doses to states and jurisdictions, but the vaccine remains in high demand. The vaccine is manufactured by the small Danish company Bavarian Nordic. These additional 786,000 doses were previously stored at a plant in Denmark, awaiting the completion of an inspection and authorization of the vaccine plant by the Food and Drug Administration. The agency announced on July 27 that both the vaccine doses and the manufacturing plant met standards.

With the announcement of these additional doses, the vaccine allocation plan is also being updated to take into account two important factors: the number of people at high risk in a jurisdiction and the number of new cases reported since the last vaccine allocation.

“This update gives greater weight to prioritizing vaccines to areas with the greatest number of people at risk, which includes men who have sex with men who have HIV or who are eligible for HIV pre-exposure prophylaxis, while still considering where we are seeing cases increase,” said Capt. Jennifer McQuiston, DVM, deputy director of the division of high consequence pathogens and pathology at the CDC.

Capt.McQuiston also provided additional demographic information on the U.S. outbreak. The median age of people with confirmed cases is 35 years old, with a range from 17 to 76. (This does not include the two cases in children reported on July 22.) Of the cases where sex at birth was provided, 99% were individuals assigned male sex at birth. In cases with reported ethnicity and race, 37% were non-Hispanic White people, 31% were Hispanic/Latino, 27% were Black or African American, and 4% were of Asian descent. The most common symptoms were rash – present in 99% of cases – malaise, fever, and swollen lymph nodes.

HHS and CDC did not have data on how many people have received at least one dose of the monkeypox vaccine. When asked how many people need to be fully vaccinated against monkeypox to contain the outbreak, Mr. Becerra did not provide an estimate but implied that preventive vaccination could help limit the number of vaccines needed and expressed optimism about quelling the outbreak in the United States. “We believe that we have done everything we can at the federal level to work with our state and local partners and communities affected to make sure we can stay ahead of this and end this outbreak,” he said, “but everybody’s got to do their part.”

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

More than 780,000 doses of the JYNNEOS monkeypox vaccine will be available in the United States beginning July 29, the Department of Health & Human Services announced on July 28 in a press call.

HHS Secretary Xavier Becerra urged local and state public health departments to use these doses for preventive vaccination efforts to stay ahead of the virus and end the outbreak, noting that the HHS and Centers for Disease Control and Prevention do not control how vaccines are distributed at state and local levels. “We don’t have the authority to tell them what to do,” he said during the call. “We need them to work with us.”

As of July 28, there were 4,907 reported cases of monkeypox in the United States and officials expect cases will continue to rise in the coming weeks.

HHS already has distributed more 338,000 doses to states and jurisdictions, but the vaccine remains in high demand. The vaccine is manufactured by the small Danish company Bavarian Nordic. These additional 786,000 doses were previously stored at a plant in Denmark, awaiting the completion of an inspection and authorization of the vaccine plant by the Food and Drug Administration. The agency announced on July 27 that both the vaccine doses and the manufacturing plant met standards.

With the announcement of these additional doses, the vaccine allocation plan is also being updated to take into account two important factors: the number of people at high risk in a jurisdiction and the number of new cases reported since the last vaccine allocation.

“This update gives greater weight to prioritizing vaccines to areas with the greatest number of people at risk, which includes men who have sex with men who have HIV or who are eligible for HIV pre-exposure prophylaxis, while still considering where we are seeing cases increase,” said Capt. Jennifer McQuiston, DVM, deputy director of the division of high consequence pathogens and pathology at the CDC.

Capt.McQuiston also provided additional demographic information on the U.S. outbreak. The median age of people with confirmed cases is 35 years old, with a range from 17 to 76. (This does not include the two cases in children reported on July 22.) Of the cases where sex at birth was provided, 99% were individuals assigned male sex at birth. In cases with reported ethnicity and race, 37% were non-Hispanic White people, 31% were Hispanic/Latino, 27% were Black or African American, and 4% were of Asian descent. The most common symptoms were rash – present in 99% of cases – malaise, fever, and swollen lymph nodes.

HHS and CDC did not have data on how many people have received at least one dose of the monkeypox vaccine. When asked how many people need to be fully vaccinated against monkeypox to contain the outbreak, Mr. Becerra did not provide an estimate but implied that preventive vaccination could help limit the number of vaccines needed and expressed optimism about quelling the outbreak in the United States. “We believe that we have done everything we can at the federal level to work with our state and local partners and communities affected to make sure we can stay ahead of this and end this outbreak,” he said, “but everybody’s got to do their part.”

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

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

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

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

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

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

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