Federal Practitioner

Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.

This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.

Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.

“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”

Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.

To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.

The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).

After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.

These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.

More studies are needed to explore this relation, said Dr. Achebe.
 

The challenge of self-reported use

The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.

It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”

And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”

This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.

Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.

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

Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.

This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.

Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.

“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”

Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.

To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.

The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).

After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.

These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.

More studies are needed to explore this relation, said Dr. Achebe.
 

The challenge of self-reported use

The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.

It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”

And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”

This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.

Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.

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

Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.

This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.

Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.

“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”

Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.

To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.

The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).

After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.

These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.

More studies are needed to explore this relation, said Dr. Achebe.
 

The challenge of self-reported use

The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.

It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”

And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”

This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.

Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.

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

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.

However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”

The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”

In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”

For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.

Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.

Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.

The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.

In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.

In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”

Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”

Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.

However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”

The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”

In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”

For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.

Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.

Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.

The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.

In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.

In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”

Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”

Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.

However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”

The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”

In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”

For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.

Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.

Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.

The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.

In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.

In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”

Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”

Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.

That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.

An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.

All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.

Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.

Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.

“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.

He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.

In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
 

More data, including on overall survival

Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).

They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.

The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.

In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.

The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).

In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).

Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.

It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
 

Hypothesis-generating study

Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.

James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.

“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.

The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.

That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.

An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.

All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.

Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.

Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.

“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.

He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.

In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
 

More data, including on overall survival

Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).

They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.

The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.

In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.

The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).

In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).

Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.

It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
 

Hypothesis-generating study

Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.

James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.

“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.

The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.

That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.

An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.

All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.

Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.

Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.

“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.

He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.

In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
 

More data, including on overall survival

Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).

They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.

The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.

In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.

The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).

In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).

Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.

It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
 

Hypothesis-generating study

Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.

James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.

“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.

The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Some medical societies feature sessions at their annual meetings that feel like they’re 24 hours long, yet few have the courage to schedule a session that actually runs all day and all night. But the five societies sponsoring the IDWeek conference had that courage. The first 24 hours of the meeting was devoted to the most pressing infectious-disease crisis of the last 100 years: the COVID-19 pandemic. They called it “COVID-19: Chasing the Sun.”

Dr. Fauci predicts a vaccine answer in mid-November

In the first segment, at 10 am Eastern time, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and the nation’s top infectious-disease expert, began the day by noting that five of the six companies the US invested in to develop a vaccine are conducting phase 3 trials. He said, “we feel confident that we will have an answer likely in mid-November to the beginning of December as to whether we have a safe and effective vaccine”. He added he was “cautiously optimistic” that “we will have a safe and effective vaccine by the end of the year, which we can begin to distribute as we go into 2021.” He highlighted the COVID-19 Prevention Network website for more information on the trials.

Glaring racial health disparities in U.S.

Some of the most glaring health disparities surrounding COVID-19 in the United States were described by Carlos del Rio, MD, professor of medicine at Emory University in Atlanta, Georgia. He pointed out that while white people have about 23 cases per 10,000 population, Blacks have about 62 cases per 10,000, and Latinos have 73 cases per 10,000. While whites don’t see a huge jump in cases until age 80, he said, “among Blacks and Latinos you start seeing that huge increase at a younger age. In fact, starting at age 20, you start seeing a major, major change.”

COVID-19 diagnostics

Audrey Odom John, MD, PhD, chief of pediatric infectious diseases at Children’s Hospital of Philadelphia, is working on a new way of diagnosing COVID-19 infection in children by testing their breath. “We’re really taking advantage of a fundamental biological fact, which is that people stink,” she said. Breath shows the health of the body as a whole, “and it’s easy to see how breath volatiles might arise from a respiratory infection.” Testing breath is easy and inexpensive, which makes it particularly attractive as a potential test globally, she said.

Long-term effects of COVID-19

Post-COVID illness threatens to overwhelm the health system in the United States, even if only 1% of the 8 million people who have been infected have some sort of long-term deficit, “which would be a very conservative estimate,” said John O’Horo, MD, MPH, with the Mayo Clinic in Rochester, Minn. Neurologic dysfunction is going to be a “fairly significant thing to keep an eye on,” he added. Preeti Malani, MD, chief health officer in infectious diseases at the University of Michigan, Ann Arbor, said the emotional aspects of the illness are “striking” and may be the major long-term effect for most patients.

Challenging cases in COVID-19: Through fire and water

In a case presented to panelists during an afternoon session, a Mexican-born woman, 42, presents to urgent care with fever, dyspnea, dry cough, and pleuritic pain, for over a week. Multiple family members have had recent respiratory illness as well. She is obese, on no medications, was not traveling. She’s a nonsmoker and lives in a multigenerational household in the Mission District of San Francisco. Her heart rate is 116, respiratory rate is 36, and her oxygen saturation on room air is 77%. She is admitted to a local hospital and quickly declines, is intubated and started on hydroxychloroquine (HCQ). One day later she is transferred to a hospital for consideration of extracorporeal membrane oxygenation (ECMO).

Panelists were asked a variety of questions about how they would treat this patient. For example, would they continue HCQ? Ravina Kullar, PharmD, MPH, an infectious disease expert from Newport Beach, Calif., answered that she would not continue the HCQ because of lack of evidence and potential harms. Asked whether she would start remdesivir, Dr. Kullar said she would steer her away from that if the patient developed renal failure. Co-moderator Peter Chin-Hong, MD, a medical educator with the University of California, San Francisco, noted that contact tracing will be important as the patient returns to her housing-dense community.
 

In-hospital infection prevention

The CDC acknowledged aerosol spread of COVID-19 this month, but David Weber, MD, MPH, professor in infectious diseases at the University of North Carolina at Chapel Hill, said, “this does not change anything we need to do in the hospital,” as long as protective pandemic protocols continue to be followed.

There is no evidence, he noted, that SARS-CoV-2 is transmitted far enough that a hospitalized patient could infect people in other rooms or corridors or floors. Opening windows in COVID-19 patients’ rooms is “not an option,” he said, and could be harmful as fungal elements in outside air may introduce new pathogens. The degree to which improved ventilation systems reduce transmission has not been identified and studies are needed to look at that, he said.
 

Preventing COVID transmission in the community

Mary-Margaret Fill, MD, deputy state epidemiologist in Tennessee, highlighted COVID-19’s spread in prisons. As of mid-October, she said, there are more than 147,000 cases among the U.S. prison population and there have been 1,246 deaths. This translates to a case rate of about 9800 cases per 100,000 people, she said, “double the highest case rate for any state in the country and over three times greater than our national case rate of about 2,500 cases per 100,000 persons.”

Testing varies widely, she noted. For instance, some states test only new prisoners, and some test only when they are symptomatic. One of the strategies to fight this spread is having staff, who go in and out of the community, be assigned to work with only certain groups at a prison. Another is widespread testing of all prisoners. And when prisoners have to leave the prison for care or court dates, a third strategy would be quarantining them upon their return.
 

COVID-19 vaccines

As the session stretched into the evening in the United States, Mary Marovich, MD, director of vaccine research, AIDS division, with the National Institute of Allergy and Infectious Diseases and the National Institutes of Health, said while each of the government-funded vaccine studies has its own trial, there are standardized objectives for direct comparisons. The studies are being conducted within the same clinical trial networks, and collaborative laboratories apply the same immunoassays and define the infections in the same way. They are all randomized, placebo-controlled trials and all but one have a 30,000-volunteer sample size. She said that while a vaccine is the goal to end the pandemic, monoclonal antibodies, such as those in convalescent plasma, “may serve as a critical bridge.”

The good, the bad, and the ugly during COVID-19 in Latin America

Latin America and the Caribbean are currently the regions hardest hit by COVID-19. Gustavo D. Lopardo, of the Asociacion Panamericana de Infectologia, noted that even before the pandemic Latin America suffered from widespread poverty and inequality. While overcrowding and poverty are determining factors in the spread of the virus, diabetes and obesity – both highly prevalent – are worsening COVID outcomes.

The countries of the region have dealt with asynchronous waves of transmission within their borders by implementing different containment strategies, with dissimilar results. The presenters covered the spectrum of the pandemic, from the “ugly” in Peru, which has the highest mortality rate in the region, to the “good” in Uruguay, where testing is “winning against COVID-19.” Paradoxically, Chile has both the highest cumulative incidence and the lowest case fatality rate of COVID-19 in the region.

In the social and political turmoil imposed by COVID-19, Clóvis Arns da Cunha, MD, president of the Brazilian Society of Infectious Diseases and professor at the Federal University of Paraná, pointed out that “fake news [has become] a public health problem in Brazil” and elsewhere.
 

Diagnostics and therapeutics in Latin America

Eleven of the 15 countries with the highest death rate in the world are located in Latin America or the Caribbean. Dr. Arns de Cunha pointed out that tests are hard to come by and inadequate diagnostic testing is a major problem. Latin American countries have not been able to compete with the United States and Europe in purchasing polymerase chain reaction test kits from China and South Korea. The test is the best diagnostic tool in the first week of symptoms, but its scale-up has proved to be a challenge in Latin America.

Furthermore, the most sensitive serological markers, CLIA and ECLIA, which perform best after 2 weeks of symptom onset, are not widely available in Latin America where many patients do not have access to the public health system. The detection of silent hypoxemia in symptomatic patients with COVID-19 can save lives; hence, Arns da Cunha praised the program that distributed 100,000 digital oximeters to hundreds of cities in Brazil, targeting vulnerable populations.
 

The COVID-19 experience in Japan

Takuya Yamagishi, MD, PhD, chief of the Antimicrobial Resistance Research Center at the National Institute of Infectious Diseases in Japan, played an instrumental role in the epidemiological investigation that took place on the Diamond Princess Cruise Ship in February 2020. That COVID-19 outbreak is the largest disease outbreak involving a cruise ship to date, with 712 confirmed COVID-19 cases and 13 deaths.

The ship-based quarantine prompted a massive public health response with unique challenges. In those early days, investigators uncovered important facts about COVID-19 epidemiology, generating hot debates regarding the public health strategy at the time. Notably, the majority of asymptomatically infected persons remained asymptomatic throughout the course of the infection, transmission from asymptomatic cases was almost as likely as transmission from symptomatic cases, and isolation of passengers in their cabins prevented inter-cabin transmission but not intra-cabin transmission.
 

Swift response in Asia Pacific region

Infectious-disease experts from Taiwan, Singapore, and Australia, who have been at the forefront of clinical care, research, and policy-making, spoke about their experiences.

Taiwan was one of the first countries to adopt a swift response to COVID-19, shortly after they recognized an outbreak of pneumonia of unknown etiology in China and long before the WHO declared a public health emergency, said Ping-Ing Lee, MD, PhD, from the National Taiwan University Children’s Hospital.

The country began onboard health checks on flights from Wuhan as early as Dec. 31, 2019. Dr. Lee attributed Taiwan’s success in prevention and control of COVID-19 to the rigorous use of face masks and environmental disinfection procedures. Regarding the country’s antilockdown stance, he said, “Lockdown may be effective; however, it is associated with a tremendous economic loss.”

In his presentation on remdesivir vs corticosteroids, David Lye, MBBS, said, “I think remdesivir as an antiviral seems to work well given early, but steroids will need to be studied further in terms of its conflicting evidence in multiple well-designed RCTs as well as [their] potential side effects.” He is director of the Infectious Disease Research and Training Office, National Centre for Infectious Diseases, Singapore.

Allen C. Cheng, MBBS, PhD, of Monash University in Melbourne, noted that “control is possible. We seemed to have controlled this twice at the moment with fairly draconian action, but every day does matter.”
 

China past the first wave

China has already passed the first wave, explained Lei Zhou, MD, of the Chinese Center for Disease Control and Prevention, but there are still some small-scale resurgences. So far a total of four waves have been identified. She also mentioned that contact tracing is intense and highlighted the case of Xinfadi Market in Beijing, the site of an outbreak in June 2020.

Gui-Qiang Wang, MD, from the Department of Infectious Disease, Peking University First Hospital, emphasized the importance of a chest CT for the diagnosis of COVID-19. “In the early stage of the disease, patients may not show any symptoms; however, on CT scan you can see pneumonia. Also, early intervention of high-risk groups and monitoring of warning indicators for disease progression is extremely important,” he said.

“Early antiviral therapy is expected to stop progression, but still needs evaluation,” he said. “Convalescent plasma is safe and effective, but its source is limited; steroid therapy needs to explore appropriate population and timing; and thymosin α is safe, and its effect on outcomes needs large-sample clinical trial.”

Time to Call for an ‘Arab CDC?’

The eastern Mediterranean is geographically, politically, economically, and religiously a very distinct and sensitive region, and “COVID-19 is an added insult to this already frail region of the world,” said Zaid Haddadin, MD, Vanderbilt University Medical Center, Nashville, Tenn.

Poor healthcare and poor public health services are a consequence of weak and fragile governments and infrastructure, the result of war and regional conflicts in many countries. Millions of war refugees live in camps with high population densities and shared facilities, which makes social distancing and community mitigation very challenging. Moreover, the culture includes frequent large social gatherings. Millions of pilgrims visit holy sites in different cities in these countries. There is also movement due to trade and tourism. Travel restrictions are challenging, and there is limited comprehension of precautionary measures.

Najwa Khuri-Bulos, professor of pediatrics and infectious diseases at the University of Jordan, was part of a task force headed by the country’s Ministry of Health. A lockdown was implemented, which helped flatten the curve, but the loosening of restrictions has led to a recent increase in cases. She said, “No country can succeed in controlling spread without the regional collaboration. Perhaps it is time to adopt the call for an Arab CDC.”
 

Africa is “not out of the woods yet”

The Africa CDC has three key pillars as the foundation for their COVID-19 strategy: preventing transmission, preventing deaths, and preventing social harm, according to Raji Tajudeen, MBBS, FWACP, MPH, head of the agency’s Public Health Institutes and Research Division. Africa, with 1.5 million cases of COVID-19, accounts for 5% of global cases. With a recovery rate of 83% and a case fatality rate of 2.4%, the African continent has fared much better than the rest of the world. “Significant improvements have been made, but we are not out of the woods yet,” he cautioned.

Richard Lessells, PhD, from the University of KwaZulu-Natal, agreed. “Unfortunately, South Africa has not been spared from the worst effects of this pandemic despite what you might read in the press and scientific coverage.” He added, “Over 50% of cases and up to two thirds of the deaths in the African region are coming from South Africa.” A bigger challenge for South Africa has been maintaining essential health services during the COVID-19 pandemic, especially since it is also at the heart of the HIV pandemic. On the brighter side, HIV itself has not emerged as a risk factor for COVID-19 infection or severe disease in South Africa.

Dimie Ogoina, MBBS, FWACP, president of the Nigerian Infectious Diseases Society, stated that COVID-19 has significantly affected access to healthcare in Nigeria, particularly immunizations and antenatal care. Immunization uptake is likely to have dropped by 50% in the country.
 

Diagnostic pitfalls in COVID-19

Technical errors associated with the SARS-CoV-2 diagnostic pipeline are a major source of variations in diagnosis, explained Jim Huggett, PhD, senior lecturer, analytical microbiology, University of Surrey, Guildford, England. He believes that PCR assays are currently too biased for a single cutoff to be broadly used, and false-positive signals are most likely because of contamination.

Dana Wolf, MD, Clinical Virology Unit, Hadassah Hebrew University Medical Center in Israel, presented a large-scale data analysis of more than 133,000 pooled samples. Such a pooling strategy appeared to be highly efficient for a wide range of prevalence rates (<1% to 6%). “Our empirical evidence strongly projects on the feasibility and benefits of pooling in the current pandemic setting, to enhance continued surveillance, control, and community reopening,” she said.

Corine Geurts van Kessel, MD, PhD, Department of Virology, Erasmus University Rotterdam (the Netherlands), discussing antibodies testing for SARS-CoV-2, pointed out that disease severity can affect testing accuracy. “Reinfection cases tell us that we cannot rely on immunity acquired by natural infection to confer herd immunity,” she said.
 

Misinformation in the first digital pandemic

The world is not only facing a devastating pandemic, but also an alarming “infodemic” of misinformation. Between January and March 2020, a new COVID-19–related tweet appeared on Twitter every 45 milliseconds. Müge Çevik, MD, MSc, MRCP, an infectious disease clinician, scientist, and science communicator, said that “the greatest challenge for science communication is reaching the audience.”

People have always been skeptical of science reporting by journalists and would rather have scientists communicate with them directly, she noted. Science communication plays a dual role. “On one hand is the need to promote science to a wide audience in order to inform and educate and inspire the next generation of scientists, and on the other hand there is also a need to engage effectively in public dialogue,” she added. Dr. Çevik and colleagues think that “The responsibility of academics should not end with finding the truth. It should end after communicating it.”
 

Treatment in the ICU

Matteo Bassetti, MD, with the University of Genoa (Italy), who was asked about when to use remdesivir in the intensive care unit and for how long, said, “In the majority of cases, 5 days is probably enough.” However, if there is high viremia, he said, physicians may choose to continue the regimen beyond 5 days. Data show it is important to prescribe this drug for patients with oxygen support in an early phase, within 10 days of the first symptoms, he added. “In the late phase, there is a very limited role for remdesivir, as we know that we are already out of the viremic phase.” He also emphasized that there is no role for hydroxychloroquine or lopinavir-ritonavir.

Breaking the chains of transmission

During the wrap-up session, former US CDC Director Tom Frieden, MD, said, “We’re not even halfway through it” about the pandemic trajectory. “And we have to be very clear that the risk of explosive spread will not end with a vaccine.” He is now president and CEO of Resolve to Save Lives.

Different parts of the world will have very different experiences, Dr. Frieden said, noting that Africa, where 4% of the population is older than 65, has a very different risk level than Europe and the United States, where 10%-20% of people are in older age groups.

“We need a one-two punch,” he noted, first preventing spread, and when it does happen, boxing it in. Mask wearing is essential. “States in the US that mandated universal mask-wearing experienced much more rapid declines (in cases) for every 5 days the mandate was in place.”

Michael Ryan, MD, executive director for the WHO’s Health Emergencies Programme, added, “We need to collectively recommit to winning this game. We know how to break the chains of transmission. We need recommitment to a scientific, societal, and political strategy, and an alliance – a contract – between those entities to try to move us forward.”

This article first appeared on Medscape.com.

Some medical societies feature sessions at their annual meetings that feel like they’re 24 hours long, yet few have the courage to schedule a session that actually runs all day and all night. But the five societies sponsoring the IDWeek conference had that courage. The first 24 hours of the meeting was devoted to the most pressing infectious-disease crisis of the last 100 years: the COVID-19 pandemic. They called it “COVID-19: Chasing the Sun.”

Dr. Fauci predicts a vaccine answer in mid-November

In the first segment, at 10 am Eastern time, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and the nation’s top infectious-disease expert, began the day by noting that five of the six companies the US invested in to develop a vaccine are conducting phase 3 trials. He said, “we feel confident that we will have an answer likely in mid-November to the beginning of December as to whether we have a safe and effective vaccine”. He added he was “cautiously optimistic” that “we will have a safe and effective vaccine by the end of the year, which we can begin to distribute as we go into 2021.” He highlighted the COVID-19 Prevention Network website for more information on the trials.

Glaring racial health disparities in U.S.

Some of the most glaring health disparities surrounding COVID-19 in the United States were described by Carlos del Rio, MD, professor of medicine at Emory University in Atlanta, Georgia. He pointed out that while white people have about 23 cases per 10,000 population, Blacks have about 62 cases per 10,000, and Latinos have 73 cases per 10,000. While whites don’t see a huge jump in cases until age 80, he said, “among Blacks and Latinos you start seeing that huge increase at a younger age. In fact, starting at age 20, you start seeing a major, major change.”

COVID-19 diagnostics

Audrey Odom John, MD, PhD, chief of pediatric infectious diseases at Children’s Hospital of Philadelphia, is working on a new way of diagnosing COVID-19 infection in children by testing their breath. “We’re really taking advantage of a fundamental biological fact, which is that people stink,” she said. Breath shows the health of the body as a whole, “and it’s easy to see how breath volatiles might arise from a respiratory infection.” Testing breath is easy and inexpensive, which makes it particularly attractive as a potential test globally, she said.

Long-term effects of COVID-19

Post-COVID illness threatens to overwhelm the health system in the United States, even if only 1% of the 8 million people who have been infected have some sort of long-term deficit, “which would be a very conservative estimate,” said John O’Horo, MD, MPH, with the Mayo Clinic in Rochester, Minn. Neurologic dysfunction is going to be a “fairly significant thing to keep an eye on,” he added. Preeti Malani, MD, chief health officer in infectious diseases at the University of Michigan, Ann Arbor, said the emotional aspects of the illness are “striking” and may be the major long-term effect for most patients.

Challenging cases in COVID-19: Through fire and water

In a case presented to panelists during an afternoon session, a Mexican-born woman, 42, presents to urgent care with fever, dyspnea, dry cough, and pleuritic pain, for over a week. Multiple family members have had recent respiratory illness as well. She is obese, on no medications, was not traveling. She’s a nonsmoker and lives in a multigenerational household in the Mission District of San Francisco. Her heart rate is 116, respiratory rate is 36, and her oxygen saturation on room air is 77%. She is admitted to a local hospital and quickly declines, is intubated and started on hydroxychloroquine (HCQ). One day later she is transferred to a hospital for consideration of extracorporeal membrane oxygenation (ECMO).

Panelists were asked a variety of questions about how they would treat this patient. For example, would they continue HCQ? Ravina Kullar, PharmD, MPH, an infectious disease expert from Newport Beach, Calif., answered that she would not continue the HCQ because of lack of evidence and potential harms. Asked whether she would start remdesivir, Dr. Kullar said she would steer her away from that if the patient developed renal failure. Co-moderator Peter Chin-Hong, MD, a medical educator with the University of California, San Francisco, noted that contact tracing will be important as the patient returns to her housing-dense community.
 

In-hospital infection prevention

The CDC acknowledged aerosol spread of COVID-19 this month, but David Weber, MD, MPH, professor in infectious diseases at the University of North Carolina at Chapel Hill, said, “this does not change anything we need to do in the hospital,” as long as protective pandemic protocols continue to be followed.

There is no evidence, he noted, that SARS-CoV-2 is transmitted far enough that a hospitalized patient could infect people in other rooms or corridors or floors. Opening windows in COVID-19 patients’ rooms is “not an option,” he said, and could be harmful as fungal elements in outside air may introduce new pathogens. The degree to which improved ventilation systems reduce transmission has not been identified and studies are needed to look at that, he said.
 

Preventing COVID transmission in the community

Mary-Margaret Fill, MD, deputy state epidemiologist in Tennessee, highlighted COVID-19’s spread in prisons. As of mid-October, she said, there are more than 147,000 cases among the U.S. prison population and there have been 1,246 deaths. This translates to a case rate of about 9800 cases per 100,000 people, she said, “double the highest case rate for any state in the country and over three times greater than our national case rate of about 2,500 cases per 100,000 persons.”

Testing varies widely, she noted. For instance, some states test only new prisoners, and some test only when they are symptomatic. One of the strategies to fight this spread is having staff, who go in and out of the community, be assigned to work with only certain groups at a prison. Another is widespread testing of all prisoners. And when prisoners have to leave the prison for care or court dates, a third strategy would be quarantining them upon their return.
 

COVID-19 vaccines

As the session stretched into the evening in the United States, Mary Marovich, MD, director of vaccine research, AIDS division, with the National Institute of Allergy and Infectious Diseases and the National Institutes of Health, said while each of the government-funded vaccine studies has its own trial, there are standardized objectives for direct comparisons. The studies are being conducted within the same clinical trial networks, and collaborative laboratories apply the same immunoassays and define the infections in the same way. They are all randomized, placebo-controlled trials and all but one have a 30,000-volunteer sample size. She said that while a vaccine is the goal to end the pandemic, monoclonal antibodies, such as those in convalescent plasma, “may serve as a critical bridge.”

The good, the bad, and the ugly during COVID-19 in Latin America

Latin America and the Caribbean are currently the regions hardest hit by COVID-19. Gustavo D. Lopardo, of the Asociacion Panamericana de Infectologia, noted that even before the pandemic Latin America suffered from widespread poverty and inequality. While overcrowding and poverty are determining factors in the spread of the virus, diabetes and obesity – both highly prevalent – are worsening COVID outcomes.

The countries of the region have dealt with asynchronous waves of transmission within their borders by implementing different containment strategies, with dissimilar results. The presenters covered the spectrum of the pandemic, from the “ugly” in Peru, which has the highest mortality rate in the region, to the “good” in Uruguay, where testing is “winning against COVID-19.” Paradoxically, Chile has both the highest cumulative incidence and the lowest case fatality rate of COVID-19 in the region.

In the social and political turmoil imposed by COVID-19, Clóvis Arns da Cunha, MD, president of the Brazilian Society of Infectious Diseases and professor at the Federal University of Paraná, pointed out that “fake news [has become] a public health problem in Brazil” and elsewhere.
 

Diagnostics and therapeutics in Latin America

Eleven of the 15 countries with the highest death rate in the world are located in Latin America or the Caribbean. Dr. Arns de Cunha pointed out that tests are hard to come by and inadequate diagnostic testing is a major problem. Latin American countries have not been able to compete with the United States and Europe in purchasing polymerase chain reaction test kits from China and South Korea. The test is the best diagnostic tool in the first week of symptoms, but its scale-up has proved to be a challenge in Latin America.

Furthermore, the most sensitive serological markers, CLIA and ECLIA, which perform best after 2 weeks of symptom onset, are not widely available in Latin America where many patients do not have access to the public health system. The detection of silent hypoxemia in symptomatic patients with COVID-19 can save lives; hence, Arns da Cunha praised the program that distributed 100,000 digital oximeters to hundreds of cities in Brazil, targeting vulnerable populations.
 

The COVID-19 experience in Japan

Takuya Yamagishi, MD, PhD, chief of the Antimicrobial Resistance Research Center at the National Institute of Infectious Diseases in Japan, played an instrumental role in the epidemiological investigation that took place on the Diamond Princess Cruise Ship in February 2020. That COVID-19 outbreak is the largest disease outbreak involving a cruise ship to date, with 712 confirmed COVID-19 cases and 13 deaths.

The ship-based quarantine prompted a massive public health response with unique challenges. In those early days, investigators uncovered important facts about COVID-19 epidemiology, generating hot debates regarding the public health strategy at the time. Notably, the majority of asymptomatically infected persons remained asymptomatic throughout the course of the infection, transmission from asymptomatic cases was almost as likely as transmission from symptomatic cases, and isolation of passengers in their cabins prevented inter-cabin transmission but not intra-cabin transmission.
 

Swift response in Asia Pacific region

Infectious-disease experts from Taiwan, Singapore, and Australia, who have been at the forefront of clinical care, research, and policy-making, spoke about their experiences.

Taiwan was one of the first countries to adopt a swift response to COVID-19, shortly after they recognized an outbreak of pneumonia of unknown etiology in China and long before the WHO declared a public health emergency, said Ping-Ing Lee, MD, PhD, from the National Taiwan University Children’s Hospital.

The country began onboard health checks on flights from Wuhan as early as Dec. 31, 2019. Dr. Lee attributed Taiwan’s success in prevention and control of COVID-19 to the rigorous use of face masks and environmental disinfection procedures. Regarding the country’s antilockdown stance, he said, “Lockdown may be effective; however, it is associated with a tremendous economic loss.”

In his presentation on remdesivir vs corticosteroids, David Lye, MBBS, said, “I think remdesivir as an antiviral seems to work well given early, but steroids will need to be studied further in terms of its conflicting evidence in multiple well-designed RCTs as well as [their] potential side effects.” He is director of the Infectious Disease Research and Training Office, National Centre for Infectious Diseases, Singapore.

Allen C. Cheng, MBBS, PhD, of Monash University in Melbourne, noted that “control is possible. We seemed to have controlled this twice at the moment with fairly draconian action, but every day does matter.”
 

China past the first wave

China has already passed the first wave, explained Lei Zhou, MD, of the Chinese Center for Disease Control and Prevention, but there are still some small-scale resurgences. So far a total of four waves have been identified. She also mentioned that contact tracing is intense and highlighted the case of Xinfadi Market in Beijing, the site of an outbreak in June 2020.

Gui-Qiang Wang, MD, from the Department of Infectious Disease, Peking University First Hospital, emphasized the importance of a chest CT for the diagnosis of COVID-19. “In the early stage of the disease, patients may not show any symptoms; however, on CT scan you can see pneumonia. Also, early intervention of high-risk groups and monitoring of warning indicators for disease progression is extremely important,” he said.

“Early antiviral therapy is expected to stop progression, but still needs evaluation,” he said. “Convalescent plasma is safe and effective, but its source is limited; steroid therapy needs to explore appropriate population and timing; and thymosin α is safe, and its effect on outcomes needs large-sample clinical trial.”

Time to Call for an ‘Arab CDC?’

The eastern Mediterranean is geographically, politically, economically, and religiously a very distinct and sensitive region, and “COVID-19 is an added insult to this already frail region of the world,” said Zaid Haddadin, MD, Vanderbilt University Medical Center, Nashville, Tenn.

Poor healthcare and poor public health services are a consequence of weak and fragile governments and infrastructure, the result of war and regional conflicts in many countries. Millions of war refugees live in camps with high population densities and shared facilities, which makes social distancing and community mitigation very challenging. Moreover, the culture includes frequent large social gatherings. Millions of pilgrims visit holy sites in different cities in these countries. There is also movement due to trade and tourism. Travel restrictions are challenging, and there is limited comprehension of precautionary measures.

Najwa Khuri-Bulos, professor of pediatrics and infectious diseases at the University of Jordan, was part of a task force headed by the country’s Ministry of Health. A lockdown was implemented, which helped flatten the curve, but the loosening of restrictions has led to a recent increase in cases. She said, “No country can succeed in controlling spread without the regional collaboration. Perhaps it is time to adopt the call for an Arab CDC.”
 

Africa is “not out of the woods yet”

The Africa CDC has three key pillars as the foundation for their COVID-19 strategy: preventing transmission, preventing deaths, and preventing social harm, according to Raji Tajudeen, MBBS, FWACP, MPH, head of the agency’s Public Health Institutes and Research Division. Africa, with 1.5 million cases of COVID-19, accounts for 5% of global cases. With a recovery rate of 83% and a case fatality rate of 2.4%, the African continent has fared much better than the rest of the world. “Significant improvements have been made, but we are not out of the woods yet,” he cautioned.

Richard Lessells, PhD, from the University of KwaZulu-Natal, agreed. “Unfortunately, South Africa has not been spared from the worst effects of this pandemic despite what you might read in the press and scientific coverage.” He added, “Over 50% of cases and up to two thirds of the deaths in the African region are coming from South Africa.” A bigger challenge for South Africa has been maintaining essential health services during the COVID-19 pandemic, especially since it is also at the heart of the HIV pandemic. On the brighter side, HIV itself has not emerged as a risk factor for COVID-19 infection or severe disease in South Africa.

Dimie Ogoina, MBBS, FWACP, president of the Nigerian Infectious Diseases Society, stated that COVID-19 has significantly affected access to healthcare in Nigeria, particularly immunizations and antenatal care. Immunization uptake is likely to have dropped by 50% in the country.
 

Diagnostic pitfalls in COVID-19

Technical errors associated with the SARS-CoV-2 diagnostic pipeline are a major source of variations in diagnosis, explained Jim Huggett, PhD, senior lecturer, analytical microbiology, University of Surrey, Guildford, England. He believes that PCR assays are currently too biased for a single cutoff to be broadly used, and false-positive signals are most likely because of contamination.

Dana Wolf, MD, Clinical Virology Unit, Hadassah Hebrew University Medical Center in Israel, presented a large-scale data analysis of more than 133,000 pooled samples. Such a pooling strategy appeared to be highly efficient for a wide range of prevalence rates (<1% to 6%). “Our empirical evidence strongly projects on the feasibility and benefits of pooling in the current pandemic setting, to enhance continued surveillance, control, and community reopening,” she said.

Corine Geurts van Kessel, MD, PhD, Department of Virology, Erasmus University Rotterdam (the Netherlands), discussing antibodies testing for SARS-CoV-2, pointed out that disease severity can affect testing accuracy. “Reinfection cases tell us that we cannot rely on immunity acquired by natural infection to confer herd immunity,” she said.
 

Misinformation in the first digital pandemic

The world is not only facing a devastating pandemic, but also an alarming “infodemic” of misinformation. Between January and March 2020, a new COVID-19–related tweet appeared on Twitter every 45 milliseconds. Müge Çevik, MD, MSc, MRCP, an infectious disease clinician, scientist, and science communicator, said that “the greatest challenge for science communication is reaching the audience.”

People have always been skeptical of science reporting by journalists and would rather have scientists communicate with them directly, she noted. Science communication plays a dual role. “On one hand is the need to promote science to a wide audience in order to inform and educate and inspire the next generation of scientists, and on the other hand there is also a need to engage effectively in public dialogue,” she added. Dr. Çevik and colleagues think that “The responsibility of academics should not end with finding the truth. It should end after communicating it.”
 

Treatment in the ICU

Matteo Bassetti, MD, with the University of Genoa (Italy), who was asked about when to use remdesivir in the intensive care unit and for how long, said, “In the majority of cases, 5 days is probably enough.” However, if there is high viremia, he said, physicians may choose to continue the regimen beyond 5 days. Data show it is important to prescribe this drug for patients with oxygen support in an early phase, within 10 days of the first symptoms, he added. “In the late phase, there is a very limited role for remdesivir, as we know that we are already out of the viremic phase.” He also emphasized that there is no role for hydroxychloroquine or lopinavir-ritonavir.

Breaking the chains of transmission

During the wrap-up session, former US CDC Director Tom Frieden, MD, said, “We’re not even halfway through it” about the pandemic trajectory. “And we have to be very clear that the risk of explosive spread will not end with a vaccine.” He is now president and CEO of Resolve to Save Lives.

Different parts of the world will have very different experiences, Dr. Frieden said, noting that Africa, where 4% of the population is older than 65, has a very different risk level than Europe and the United States, where 10%-20% of people are in older age groups.

“We need a one-two punch,” he noted, first preventing spread, and when it does happen, boxing it in. Mask wearing is essential. “States in the US that mandated universal mask-wearing experienced much more rapid declines (in cases) for every 5 days the mandate was in place.”

Michael Ryan, MD, executive director for the WHO’s Health Emergencies Programme, added, “We need to collectively recommit to winning this game. We know how to break the chains of transmission. We need recommitment to a scientific, societal, and political strategy, and an alliance – a contract – between those entities to try to move us forward.”

This article first appeared on Medscape.com.

Some medical societies feature sessions at their annual meetings that feel like they’re 24 hours long, yet few have the courage to schedule a session that actually runs all day and all night. But the five societies sponsoring the IDWeek conference had that courage. The first 24 hours of the meeting was devoted to the most pressing infectious-disease crisis of the last 100 years: the COVID-19 pandemic. They called it “COVID-19: Chasing the Sun.”

Dr. Fauci predicts a vaccine answer in mid-November

In the first segment, at 10 am Eastern time, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and the nation’s top infectious-disease expert, began the day by noting that five of the six companies the US invested in to develop a vaccine are conducting phase 3 trials. He said, “we feel confident that we will have an answer likely in mid-November to the beginning of December as to whether we have a safe and effective vaccine”. He added he was “cautiously optimistic” that “we will have a safe and effective vaccine by the end of the year, which we can begin to distribute as we go into 2021.” He highlighted the COVID-19 Prevention Network website for more information on the trials.

Glaring racial health disparities in U.S.

Some of the most glaring health disparities surrounding COVID-19 in the United States were described by Carlos del Rio, MD, professor of medicine at Emory University in Atlanta, Georgia. He pointed out that while white people have about 23 cases per 10,000 population, Blacks have about 62 cases per 10,000, and Latinos have 73 cases per 10,000. While whites don’t see a huge jump in cases until age 80, he said, “among Blacks and Latinos you start seeing that huge increase at a younger age. In fact, starting at age 20, you start seeing a major, major change.”

COVID-19 diagnostics

Audrey Odom John, MD, PhD, chief of pediatric infectious diseases at Children’s Hospital of Philadelphia, is working on a new way of diagnosing COVID-19 infection in children by testing their breath. “We’re really taking advantage of a fundamental biological fact, which is that people stink,” she said. Breath shows the health of the body as a whole, “and it’s easy to see how breath volatiles might arise from a respiratory infection.” Testing breath is easy and inexpensive, which makes it particularly attractive as a potential test globally, she said.

Long-term effects of COVID-19

Post-COVID illness threatens to overwhelm the health system in the United States, even if only 1% of the 8 million people who have been infected have some sort of long-term deficit, “which would be a very conservative estimate,” said John O’Horo, MD, MPH, with the Mayo Clinic in Rochester, Minn. Neurologic dysfunction is going to be a “fairly significant thing to keep an eye on,” he added. Preeti Malani, MD, chief health officer in infectious diseases at the University of Michigan, Ann Arbor, said the emotional aspects of the illness are “striking” and may be the major long-term effect for most patients.

Challenging cases in COVID-19: Through fire and water

In a case presented to panelists during an afternoon session, a Mexican-born woman, 42, presents to urgent care with fever, dyspnea, dry cough, and pleuritic pain, for over a week. Multiple family members have had recent respiratory illness as well. She is obese, on no medications, was not traveling. She’s a nonsmoker and lives in a multigenerational household in the Mission District of San Francisco. Her heart rate is 116, respiratory rate is 36, and her oxygen saturation on room air is 77%. She is admitted to a local hospital and quickly declines, is intubated and started on hydroxychloroquine (HCQ). One day later she is transferred to a hospital for consideration of extracorporeal membrane oxygenation (ECMO).

Panelists were asked a variety of questions about how they would treat this patient. For example, would they continue HCQ? Ravina Kullar, PharmD, MPH, an infectious disease expert from Newport Beach, Calif., answered that she would not continue the HCQ because of lack of evidence and potential harms. Asked whether she would start remdesivir, Dr. Kullar said she would steer her away from that if the patient developed renal failure. Co-moderator Peter Chin-Hong, MD, a medical educator with the University of California, San Francisco, noted that contact tracing will be important as the patient returns to her housing-dense community.
 

In-hospital infection prevention

The CDC acknowledged aerosol spread of COVID-19 this month, but David Weber, MD, MPH, professor in infectious diseases at the University of North Carolina at Chapel Hill, said, “this does not change anything we need to do in the hospital,” as long as protective pandemic protocols continue to be followed.

There is no evidence, he noted, that SARS-CoV-2 is transmitted far enough that a hospitalized patient could infect people in other rooms or corridors or floors. Opening windows in COVID-19 patients’ rooms is “not an option,” he said, and could be harmful as fungal elements in outside air may introduce new pathogens. The degree to which improved ventilation systems reduce transmission has not been identified and studies are needed to look at that, he said.
 

Preventing COVID transmission in the community

Mary-Margaret Fill, MD, deputy state epidemiologist in Tennessee, highlighted COVID-19’s spread in prisons. As of mid-October, she said, there are more than 147,000 cases among the U.S. prison population and there have been 1,246 deaths. This translates to a case rate of about 9800 cases per 100,000 people, she said, “double the highest case rate for any state in the country and over three times greater than our national case rate of about 2,500 cases per 100,000 persons.”

Testing varies widely, she noted. For instance, some states test only new prisoners, and some test only when they are symptomatic. One of the strategies to fight this spread is having staff, who go in and out of the community, be assigned to work with only certain groups at a prison. Another is widespread testing of all prisoners. And when prisoners have to leave the prison for care or court dates, a third strategy would be quarantining them upon their return.
 

COVID-19 vaccines

As the session stretched into the evening in the United States, Mary Marovich, MD, director of vaccine research, AIDS division, with the National Institute of Allergy and Infectious Diseases and the National Institutes of Health, said while each of the government-funded vaccine studies has its own trial, there are standardized objectives for direct comparisons. The studies are being conducted within the same clinical trial networks, and collaborative laboratories apply the same immunoassays and define the infections in the same way. They are all randomized, placebo-controlled trials and all but one have a 30,000-volunteer sample size. She said that while a vaccine is the goal to end the pandemic, monoclonal antibodies, such as those in convalescent plasma, “may serve as a critical bridge.”

The good, the bad, and the ugly during COVID-19 in Latin America

Latin America and the Caribbean are currently the regions hardest hit by COVID-19. Gustavo D. Lopardo, of the Asociacion Panamericana de Infectologia, noted that even before the pandemic Latin America suffered from widespread poverty and inequality. While overcrowding and poverty are determining factors in the spread of the virus, diabetes and obesity – both highly prevalent – are worsening COVID outcomes.

The countries of the region have dealt with asynchronous waves of transmission within their borders by implementing different containment strategies, with dissimilar results. The presenters covered the spectrum of the pandemic, from the “ugly” in Peru, which has the highest mortality rate in the region, to the “good” in Uruguay, where testing is “winning against COVID-19.” Paradoxically, Chile has both the highest cumulative incidence and the lowest case fatality rate of COVID-19 in the region.

In the social and political turmoil imposed by COVID-19, Clóvis Arns da Cunha, MD, president of the Brazilian Society of Infectious Diseases and professor at the Federal University of Paraná, pointed out that “fake news [has become] a public health problem in Brazil” and elsewhere.
 

Diagnostics and therapeutics in Latin America

Eleven of the 15 countries with the highest death rate in the world are located in Latin America or the Caribbean. Dr. Arns de Cunha pointed out that tests are hard to come by and inadequate diagnostic testing is a major problem. Latin American countries have not been able to compete with the United States and Europe in purchasing polymerase chain reaction test kits from China and South Korea. The test is the best diagnostic tool in the first week of symptoms, but its scale-up has proved to be a challenge in Latin America.

Furthermore, the most sensitive serological markers, CLIA and ECLIA, which perform best after 2 weeks of symptom onset, are not widely available in Latin America where many patients do not have access to the public health system. The detection of silent hypoxemia in symptomatic patients with COVID-19 can save lives; hence, Arns da Cunha praised the program that distributed 100,000 digital oximeters to hundreds of cities in Brazil, targeting vulnerable populations.
 

The COVID-19 experience in Japan

Takuya Yamagishi, MD, PhD, chief of the Antimicrobial Resistance Research Center at the National Institute of Infectious Diseases in Japan, played an instrumental role in the epidemiological investigation that took place on the Diamond Princess Cruise Ship in February 2020. That COVID-19 outbreak is the largest disease outbreak involving a cruise ship to date, with 712 confirmed COVID-19 cases and 13 deaths.

The ship-based quarantine prompted a massive public health response with unique challenges. In those early days, investigators uncovered important facts about COVID-19 epidemiology, generating hot debates regarding the public health strategy at the time. Notably, the majority of asymptomatically infected persons remained asymptomatic throughout the course of the infection, transmission from asymptomatic cases was almost as likely as transmission from symptomatic cases, and isolation of passengers in their cabins prevented inter-cabin transmission but not intra-cabin transmission.
 

Swift response in Asia Pacific region

Infectious-disease experts from Taiwan, Singapore, and Australia, who have been at the forefront of clinical care, research, and policy-making, spoke about their experiences.

Taiwan was one of the first countries to adopt a swift response to COVID-19, shortly after they recognized an outbreak of pneumonia of unknown etiology in China and long before the WHO declared a public health emergency, said Ping-Ing Lee, MD, PhD, from the National Taiwan University Children’s Hospital.

The country began onboard health checks on flights from Wuhan as early as Dec. 31, 2019. Dr. Lee attributed Taiwan’s success in prevention and control of COVID-19 to the rigorous use of face masks and environmental disinfection procedures. Regarding the country’s antilockdown stance, he said, “Lockdown may be effective; however, it is associated with a tremendous economic loss.”

In his presentation on remdesivir vs corticosteroids, David Lye, MBBS, said, “I think remdesivir as an antiviral seems to work well given early, but steroids will need to be studied further in terms of its conflicting evidence in multiple well-designed RCTs as well as [their] potential side effects.” He is director of the Infectious Disease Research and Training Office, National Centre for Infectious Diseases, Singapore.

Allen C. Cheng, MBBS, PhD, of Monash University in Melbourne, noted that “control is possible. We seemed to have controlled this twice at the moment with fairly draconian action, but every day does matter.”
 

China past the first wave

China has already passed the first wave, explained Lei Zhou, MD, of the Chinese Center for Disease Control and Prevention, but there are still some small-scale resurgences. So far a total of four waves have been identified. She also mentioned that contact tracing is intense and highlighted the case of Xinfadi Market in Beijing, the site of an outbreak in June 2020.

Gui-Qiang Wang, MD, from the Department of Infectious Disease, Peking University First Hospital, emphasized the importance of a chest CT for the diagnosis of COVID-19. “In the early stage of the disease, patients may not show any symptoms; however, on CT scan you can see pneumonia. Also, early intervention of high-risk groups and monitoring of warning indicators for disease progression is extremely important,” he said.

“Early antiviral therapy is expected to stop progression, but still needs evaluation,” he said. “Convalescent plasma is safe and effective, but its source is limited; steroid therapy needs to explore appropriate population and timing; and thymosin α is safe, and its effect on outcomes needs large-sample clinical trial.”

Time to Call for an ‘Arab CDC?’

The eastern Mediterranean is geographically, politically, economically, and religiously a very distinct and sensitive region, and “COVID-19 is an added insult to this already frail region of the world,” said Zaid Haddadin, MD, Vanderbilt University Medical Center, Nashville, Tenn.

Poor healthcare and poor public health services are a consequence of weak and fragile governments and infrastructure, the result of war and regional conflicts in many countries. Millions of war refugees live in camps with high population densities and shared facilities, which makes social distancing and community mitigation very challenging. Moreover, the culture includes frequent large social gatherings. Millions of pilgrims visit holy sites in different cities in these countries. There is also movement due to trade and tourism. Travel restrictions are challenging, and there is limited comprehension of precautionary measures.

Najwa Khuri-Bulos, professor of pediatrics and infectious diseases at the University of Jordan, was part of a task force headed by the country’s Ministry of Health. A lockdown was implemented, which helped flatten the curve, but the loosening of restrictions has led to a recent increase in cases. She said, “No country can succeed in controlling spread without the regional collaboration. Perhaps it is time to adopt the call for an Arab CDC.”
 

Africa is “not out of the woods yet”

The Africa CDC has three key pillars as the foundation for their COVID-19 strategy: preventing transmission, preventing deaths, and preventing social harm, according to Raji Tajudeen, MBBS, FWACP, MPH, head of the agency’s Public Health Institutes and Research Division. Africa, with 1.5 million cases of COVID-19, accounts for 5% of global cases. With a recovery rate of 83% and a case fatality rate of 2.4%, the African continent has fared much better than the rest of the world. “Significant improvements have been made, but we are not out of the woods yet,” he cautioned.

Richard Lessells, PhD, from the University of KwaZulu-Natal, agreed. “Unfortunately, South Africa has not been spared from the worst effects of this pandemic despite what you might read in the press and scientific coverage.” He added, “Over 50% of cases and up to two thirds of the deaths in the African region are coming from South Africa.” A bigger challenge for South Africa has been maintaining essential health services during the COVID-19 pandemic, especially since it is also at the heart of the HIV pandemic. On the brighter side, HIV itself has not emerged as a risk factor for COVID-19 infection or severe disease in South Africa.

Dimie Ogoina, MBBS, FWACP, president of the Nigerian Infectious Diseases Society, stated that COVID-19 has significantly affected access to healthcare in Nigeria, particularly immunizations and antenatal care. Immunization uptake is likely to have dropped by 50% in the country.
 

Diagnostic pitfalls in COVID-19

Technical errors associated with the SARS-CoV-2 diagnostic pipeline are a major source of variations in diagnosis, explained Jim Huggett, PhD, senior lecturer, analytical microbiology, University of Surrey, Guildford, England. He believes that PCR assays are currently too biased for a single cutoff to be broadly used, and false-positive signals are most likely because of contamination.

Dana Wolf, MD, Clinical Virology Unit, Hadassah Hebrew University Medical Center in Israel, presented a large-scale data analysis of more than 133,000 pooled samples. Such a pooling strategy appeared to be highly efficient for a wide range of prevalence rates (<1% to 6%). “Our empirical evidence strongly projects on the feasibility and benefits of pooling in the current pandemic setting, to enhance continued surveillance, control, and community reopening,” she said.

Corine Geurts van Kessel, MD, PhD, Department of Virology, Erasmus University Rotterdam (the Netherlands), discussing antibodies testing for SARS-CoV-2, pointed out that disease severity can affect testing accuracy. “Reinfection cases tell us that we cannot rely on immunity acquired by natural infection to confer herd immunity,” she said.
 

Misinformation in the first digital pandemic

The world is not only facing a devastating pandemic, but also an alarming “infodemic” of misinformation. Between January and March 2020, a new COVID-19–related tweet appeared on Twitter every 45 milliseconds. Müge Çevik, MD, MSc, MRCP, an infectious disease clinician, scientist, and science communicator, said that “the greatest challenge for science communication is reaching the audience.”

People have always been skeptical of science reporting by journalists and would rather have scientists communicate with them directly, she noted. Science communication plays a dual role. “On one hand is the need to promote science to a wide audience in order to inform and educate and inspire the next generation of scientists, and on the other hand there is also a need to engage effectively in public dialogue,” she added. Dr. Çevik and colleagues think that “The responsibility of academics should not end with finding the truth. It should end after communicating it.”
 

Treatment in the ICU

Matteo Bassetti, MD, with the University of Genoa (Italy), who was asked about when to use remdesivir in the intensive care unit and for how long, said, “In the majority of cases, 5 days is probably enough.” However, if there is high viremia, he said, physicians may choose to continue the regimen beyond 5 days. Data show it is important to prescribe this drug for patients with oxygen support in an early phase, within 10 days of the first symptoms, he added. “In the late phase, there is a very limited role for remdesivir, as we know that we are already out of the viremic phase.” He also emphasized that there is no role for hydroxychloroquine or lopinavir-ritonavir.

Breaking the chains of transmission

During the wrap-up session, former US CDC Director Tom Frieden, MD, said, “We’re not even halfway through it” about the pandemic trajectory. “And we have to be very clear that the risk of explosive spread will not end with a vaccine.” He is now president and CEO of Resolve to Save Lives.

Different parts of the world will have very different experiences, Dr. Frieden said, noting that Africa, where 4% of the population is older than 65, has a very different risk level than Europe and the United States, where 10%-20% of people are in older age groups.

“We need a one-two punch,” he noted, first preventing spread, and when it does happen, boxing it in. Mask wearing is essential. “States in the US that mandated universal mask-wearing experienced much more rapid declines (in cases) for every 5 days the mandate was in place.”

Michael Ryan, MD, executive director for the WHO’s Health Emergencies Programme, added, “We need to collectively recommit to winning this game. We know how to break the chains of transmission. We need recommitment to a scientific, societal, and political strategy, and an alliance – a contract – between those entities to try to move us forward.”

This article first appeared on Medscape.com.

Although the efficacy of two pre-exposure prophylaxis (PrEP) regimens containing differing prodrug formulations of tenofovir are virtually identical, the balance between benefit and risk tips in favor of the combination using the older formulation, tenofovir disoproxil fumarate (TDF), a pharmacology researcher said.

An analysis of the pharmacologic profiles of TDF plus emtricitabine (FTC; Truvada and generic) with tenofovir alafenamide (TAF) plus FTC (Descovy) shows that the risk of decreased bone mineral density and renal toxicity with TDF are significantly lower than those of weight gain and related metabolic and cardiovascular problems associated with the newer tenofovir formulation TAF, according to pharmacology research fellow Andrew Hill, MD, PhD, from the University of Liverpool (England).

“I think when we’re comparing these two drugs overall, we have a clear benefit/risk, and we need to take both of these potential toxicities seriously, “ he said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases held virtually this year.

“But in my view, treating women – Black women – with TAF/FTC is a bad thing,” he continued. “I think it’s going lead to more harm, more myocardial infarctions, more cases of diabetes, and potentially more adverse birth outcomes, and I think that is a risk that is not worth taking, given that the apparent benefit in terms of bone mineral density and renal markers is a hypothesis at best, and is not translated into hard clinical endpoints.”
 

Adverse event profiles

Dr. Hill compared the side effect profiles of the two agents when used both in antiretroviral therapy (ART) in combination the integrase inhibitor dolutegravir (DTG; Tivicay), and in PrEP.

World Health Organization guidelines for first-line ART recommend the use of TDF/FTC/DTG, reserving TAF plus lamivudine (3TC) and DTG for use in special circumstances only, Dr. Hill noted.

He pointed to a pooled analysis of data from eight randomized, controlled trials of treatment-naive people living with HIV who started on ART from 2003 to 2015. The authors found that demographic factors associated with weight gain included lower CD4 cell counter, higher levels of HIV type 1 RNA, no injection drug use, female sex, and Black race.

They also found that, among nucleoside/nucleotide reverse transcriptase inhibitors, TAF was associated with more weight gain than TDF, abacavir, or zidovudine.

“This pattern is seen consistently across studies both of pre-exposure prophylaxis or treatment comparing tenofovir with either TAF or other nucleoside analogs,” he said.

The greater weight gain with TAF versus TDF was seen in both treatment trials and in the DISCOVER PrEP trial.

In addition, in a crossover trial conducted in Germany, patients who switched from TDF to TAF had an approximately 2 kg increase in body weight.

TAF has also been associated with higher grade 3 or 4 glucose and LDL cholesterol than TDF in clinical trials for the treatment of hepatitis B infections, and with higher LDL cholesterol and total cholesterol levels as well as diabetes in patients treated with the drugs in combination in the EMERALD HIV trial.

Clinical trials also tend to underestimate the real-world population of persons at highest risk for adverse events from TAF, Dr. Hill said, noting that the percentage of Black women in phase 3 trials for dolutegravir was 9%, compared with 42% among persons infected with HIV worldwide. The respective percentages for Black men are 16% versus 30%. These differences are similar across clinical trial programs for other ART agents.

“Generally, it’s women and Black people who seem to be at greatest risk for safety issues,” he said.

In the ADVANCE trial comparing TAF/FTC/DTG with TDF/FTC/DTG and a control arm of TDF, FTC and efavirenz, the mean change in weight among men after 3 years on the TAF-based regimen was a gain of 7.2 kg (15.9 lbs), compared with 5.5 kg (12 lbs) with TDF, and 2.6 kg (5.7 lbs) with the efavirenz-containing regimen.

In women enrolled in the same trial, the respective mean weight gains were 12.3 kg (27 lbs), 7.4 kg (16.3 lbs), and 5.5 kg (12 lbs).

“All of our analyses so far have shown that the weight continues to go up. We’re actually seeing people doubling in their body weight. We’ve seen some women come into clinic and their doctors don’t even recognize them because they’ve put on so much weight,” he said.

In women, most of the gain in weight occurs as limb or trunk fat, with a predominance of visceral fat.

People taking TAF in the trial were also at significantly greater risk for developing the metabolic syndrome, and at week 96, 27% of women on TAF/FTC/DTG had treatment-emergent obesity, compared with 17% for those on TDF/FTC/DTG and 11% for those on TDF/FTC/EFV. In men, the respective 96-week rates of treatment-emergent obesity were 7%, 3%, and 2%.

Clinical obesity itself is a risk factor for obstetric complications and birth outcomes, Alzheimer’s disease, type 2 diabetes, cardiovascular disease, hypertension and cancer, and an average 4-year reduction in life expectancy, Dr. Hill said. “I think it’s actually very unlikely that the [World Health Organization] guidelines will now change and allow the widespread use of TAF/FTC in combination with integrase inhibitors worldwide given these potential implications.”
 

Modern times

The bad rap that TDF gets for its alleged effects on bone mineral density and kidneys comes from studies where the drug was given in a boosted regimen that can amplify tenofovir toxicities, Dr. Hill said.

He noted that data from Gilead Sciences shows through 7 years of therapy in previously ART-naive patients, the combination of TDF/3TC/EFV showed sustained durable efficacy, no discontinuations to renal adverse effects, and no evidence of clinically relevant bone effects.

“I think we need to be very careful when we look at tenofovir and TAF. We need to look at the more modern way that these drugs are used, which is not with pharmacokinetic boosters anymore, and in that situation the toxicity profile of tenofovir/3TC – the original TDF – is very favorable,” he said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Hill presented his data, said that his clinical experience mirrors the pharmacokinetic findings.

“I certainly have strong feelings about the use of TDF in pre-exposure prophylaxis,” he said in an interview. “TDF is an effective and safe formulation of tenofovir to be used in pre-exposure prophylaxis, and one that we have more experience with. It’s the formulation of tenofovir that I use for all of my patients who are on pre-exposure prophylaxis, and I think it is the most cost-effective.’

No funding source was reported. Andrew Hill consults for Tibotec on clinical trial programs for darunavir, etravirine, and rilpivirine. Dr. Goldstein reported having no relevant disclosures.

Although the efficacy of two pre-exposure prophylaxis (PrEP) regimens containing differing prodrug formulations of tenofovir are virtually identical, the balance between benefit and risk tips in favor of the combination using the older formulation, tenofovir disoproxil fumarate (TDF), a pharmacology researcher said.

An analysis of the pharmacologic profiles of TDF plus emtricitabine (FTC; Truvada and generic) with tenofovir alafenamide (TAF) plus FTC (Descovy) shows that the risk of decreased bone mineral density and renal toxicity with TDF are significantly lower than those of weight gain and related metabolic and cardiovascular problems associated with the newer tenofovir formulation TAF, according to pharmacology research fellow Andrew Hill, MD, PhD, from the University of Liverpool (England).

“I think when we’re comparing these two drugs overall, we have a clear benefit/risk, and we need to take both of these potential toxicities seriously, “ he said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases held virtually this year.

“But in my view, treating women – Black women – with TAF/FTC is a bad thing,” he continued. “I think it’s going lead to more harm, more myocardial infarctions, more cases of diabetes, and potentially more adverse birth outcomes, and I think that is a risk that is not worth taking, given that the apparent benefit in terms of bone mineral density and renal markers is a hypothesis at best, and is not translated into hard clinical endpoints.”
 

Adverse event profiles

Dr. Hill compared the side effect profiles of the two agents when used both in antiretroviral therapy (ART) in combination the integrase inhibitor dolutegravir (DTG; Tivicay), and in PrEP.

World Health Organization guidelines for first-line ART recommend the use of TDF/FTC/DTG, reserving TAF plus lamivudine (3TC) and DTG for use in special circumstances only, Dr. Hill noted.

He pointed to a pooled analysis of data from eight randomized, controlled trials of treatment-naive people living with HIV who started on ART from 2003 to 2015. The authors found that demographic factors associated with weight gain included lower CD4 cell counter, higher levels of HIV type 1 RNA, no injection drug use, female sex, and Black race.

They also found that, among nucleoside/nucleotide reverse transcriptase inhibitors, TAF was associated with more weight gain than TDF, abacavir, or zidovudine.

“This pattern is seen consistently across studies both of pre-exposure prophylaxis or treatment comparing tenofovir with either TAF or other nucleoside analogs,” he said.

The greater weight gain with TAF versus TDF was seen in both treatment trials and in the DISCOVER PrEP trial.

In addition, in a crossover trial conducted in Germany, patients who switched from TDF to TAF had an approximately 2 kg increase in body weight.

TAF has also been associated with higher grade 3 or 4 glucose and LDL cholesterol than TDF in clinical trials for the treatment of hepatitis B infections, and with higher LDL cholesterol and total cholesterol levels as well as diabetes in patients treated with the drugs in combination in the EMERALD HIV trial.

Clinical trials also tend to underestimate the real-world population of persons at highest risk for adverse events from TAF, Dr. Hill said, noting that the percentage of Black women in phase 3 trials for dolutegravir was 9%, compared with 42% among persons infected with HIV worldwide. The respective percentages for Black men are 16% versus 30%. These differences are similar across clinical trial programs for other ART agents.

“Generally, it’s women and Black people who seem to be at greatest risk for safety issues,” he said.

In the ADVANCE trial comparing TAF/FTC/DTG with TDF/FTC/DTG and a control arm of TDF, FTC and efavirenz, the mean change in weight among men after 3 years on the TAF-based regimen was a gain of 7.2 kg (15.9 lbs), compared with 5.5 kg (12 lbs) with TDF, and 2.6 kg (5.7 lbs) with the efavirenz-containing regimen.

In women enrolled in the same trial, the respective mean weight gains were 12.3 kg (27 lbs), 7.4 kg (16.3 lbs), and 5.5 kg (12 lbs).

“All of our analyses so far have shown that the weight continues to go up. We’re actually seeing people doubling in their body weight. We’ve seen some women come into clinic and their doctors don’t even recognize them because they’ve put on so much weight,” he said.

In women, most of the gain in weight occurs as limb or trunk fat, with a predominance of visceral fat.

People taking TAF in the trial were also at significantly greater risk for developing the metabolic syndrome, and at week 96, 27% of women on TAF/FTC/DTG had treatment-emergent obesity, compared with 17% for those on TDF/FTC/DTG and 11% for those on TDF/FTC/EFV. In men, the respective 96-week rates of treatment-emergent obesity were 7%, 3%, and 2%.

Clinical obesity itself is a risk factor for obstetric complications and birth outcomes, Alzheimer’s disease, type 2 diabetes, cardiovascular disease, hypertension and cancer, and an average 4-year reduction in life expectancy, Dr. Hill said. “I think it’s actually very unlikely that the [World Health Organization] guidelines will now change and allow the widespread use of TAF/FTC in combination with integrase inhibitors worldwide given these potential implications.”
 

Modern times

The bad rap that TDF gets for its alleged effects on bone mineral density and kidneys comes from studies where the drug was given in a boosted regimen that can amplify tenofovir toxicities, Dr. Hill said.

He noted that data from Gilead Sciences shows through 7 years of therapy in previously ART-naive patients, the combination of TDF/3TC/EFV showed sustained durable efficacy, no discontinuations to renal adverse effects, and no evidence of clinically relevant bone effects.

“I think we need to be very careful when we look at tenofovir and TAF. We need to look at the more modern way that these drugs are used, which is not with pharmacokinetic boosters anymore, and in that situation the toxicity profile of tenofovir/3TC – the original TDF – is very favorable,” he said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Hill presented his data, said that his clinical experience mirrors the pharmacokinetic findings.

“I certainly have strong feelings about the use of TDF in pre-exposure prophylaxis,” he said in an interview. “TDF is an effective and safe formulation of tenofovir to be used in pre-exposure prophylaxis, and one that we have more experience with. It’s the formulation of tenofovir that I use for all of my patients who are on pre-exposure prophylaxis, and I think it is the most cost-effective.’

No funding source was reported. Andrew Hill consults for Tibotec on clinical trial programs for darunavir, etravirine, and rilpivirine. Dr. Goldstein reported having no relevant disclosures.

Although the efficacy of two pre-exposure prophylaxis (PrEP) regimens containing differing prodrug formulations of tenofovir are virtually identical, the balance between benefit and risk tips in favor of the combination using the older formulation, tenofovir disoproxil fumarate (TDF), a pharmacology researcher said.

An analysis of the pharmacologic profiles of TDF plus emtricitabine (FTC; Truvada and generic) with tenofovir alafenamide (TAF) plus FTC (Descovy) shows that the risk of decreased bone mineral density and renal toxicity with TDF are significantly lower than those of weight gain and related metabolic and cardiovascular problems associated with the newer tenofovir formulation TAF, according to pharmacology research fellow Andrew Hill, MD, PhD, from the University of Liverpool (England).

“I think when we’re comparing these two drugs overall, we have a clear benefit/risk, and we need to take both of these potential toxicities seriously, “ he said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases held virtually this year.

“But in my view, treating women – Black women – with TAF/FTC is a bad thing,” he continued. “I think it’s going lead to more harm, more myocardial infarctions, more cases of diabetes, and potentially more adverse birth outcomes, and I think that is a risk that is not worth taking, given that the apparent benefit in terms of bone mineral density and renal markers is a hypothesis at best, and is not translated into hard clinical endpoints.”
 

Adverse event profiles

Dr. Hill compared the side effect profiles of the two agents when used both in antiretroviral therapy (ART) in combination the integrase inhibitor dolutegravir (DTG; Tivicay), and in PrEP.

World Health Organization guidelines for first-line ART recommend the use of TDF/FTC/DTG, reserving TAF plus lamivudine (3TC) and DTG for use in special circumstances only, Dr. Hill noted.

He pointed to a pooled analysis of data from eight randomized, controlled trials of treatment-naive people living with HIV who started on ART from 2003 to 2015. The authors found that demographic factors associated with weight gain included lower CD4 cell counter, higher levels of HIV type 1 RNA, no injection drug use, female sex, and Black race.

They also found that, among nucleoside/nucleotide reverse transcriptase inhibitors, TAF was associated with more weight gain than TDF, abacavir, or zidovudine.

“This pattern is seen consistently across studies both of pre-exposure prophylaxis or treatment comparing tenofovir with either TAF or other nucleoside analogs,” he said.

The greater weight gain with TAF versus TDF was seen in both treatment trials and in the DISCOVER PrEP trial.

In addition, in a crossover trial conducted in Germany, patients who switched from TDF to TAF had an approximately 2 kg increase in body weight.

TAF has also been associated with higher grade 3 or 4 glucose and LDL cholesterol than TDF in clinical trials for the treatment of hepatitis B infections, and with higher LDL cholesterol and total cholesterol levels as well as diabetes in patients treated with the drugs in combination in the EMERALD HIV trial.

Clinical trials also tend to underestimate the real-world population of persons at highest risk for adverse events from TAF, Dr. Hill said, noting that the percentage of Black women in phase 3 trials for dolutegravir was 9%, compared with 42% among persons infected with HIV worldwide. The respective percentages for Black men are 16% versus 30%. These differences are similar across clinical trial programs for other ART agents.

“Generally, it’s women and Black people who seem to be at greatest risk for safety issues,” he said.

In the ADVANCE trial comparing TAF/FTC/DTG with TDF/FTC/DTG and a control arm of TDF, FTC and efavirenz, the mean change in weight among men after 3 years on the TAF-based regimen was a gain of 7.2 kg (15.9 lbs), compared with 5.5 kg (12 lbs) with TDF, and 2.6 kg (5.7 lbs) with the efavirenz-containing regimen.

In women enrolled in the same trial, the respective mean weight gains were 12.3 kg (27 lbs), 7.4 kg (16.3 lbs), and 5.5 kg (12 lbs).

“All of our analyses so far have shown that the weight continues to go up. We’re actually seeing people doubling in their body weight. We’ve seen some women come into clinic and their doctors don’t even recognize them because they’ve put on so much weight,” he said.

In women, most of the gain in weight occurs as limb or trunk fat, with a predominance of visceral fat.

People taking TAF in the trial were also at significantly greater risk for developing the metabolic syndrome, and at week 96, 27% of women on TAF/FTC/DTG had treatment-emergent obesity, compared with 17% for those on TDF/FTC/DTG and 11% for those on TDF/FTC/EFV. In men, the respective 96-week rates of treatment-emergent obesity were 7%, 3%, and 2%.

Clinical obesity itself is a risk factor for obstetric complications and birth outcomes, Alzheimer’s disease, type 2 diabetes, cardiovascular disease, hypertension and cancer, and an average 4-year reduction in life expectancy, Dr. Hill said. “I think it’s actually very unlikely that the [World Health Organization] guidelines will now change and allow the widespread use of TAF/FTC in combination with integrase inhibitors worldwide given these potential implications.”
 

Modern times

The bad rap that TDF gets for its alleged effects on bone mineral density and kidneys comes from studies where the drug was given in a boosted regimen that can amplify tenofovir toxicities, Dr. Hill said.

He noted that data from Gilead Sciences shows through 7 years of therapy in previously ART-naive patients, the combination of TDF/3TC/EFV showed sustained durable efficacy, no discontinuations to renal adverse effects, and no evidence of clinically relevant bone effects.

“I think we need to be very careful when we look at tenofovir and TAF. We need to look at the more modern way that these drugs are used, which is not with pharmacokinetic boosters anymore, and in that situation the toxicity profile of tenofovir/3TC – the original TDF – is very favorable,” he said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Hill presented his data, said that his clinical experience mirrors the pharmacokinetic findings.

“I certainly have strong feelings about the use of TDF in pre-exposure prophylaxis,” he said in an interview. “TDF is an effective and safe formulation of tenofovir to be used in pre-exposure prophylaxis, and one that we have more experience with. It’s the formulation of tenofovir that I use for all of my patients who are on pre-exposure prophylaxis, and I think it is the most cost-effective.’

No funding source was reported. Andrew Hill consults for Tibotec on clinical trial programs for darunavir, etravirine, and rilpivirine. Dr. Goldstein reported having no relevant disclosures.

A patient-centered approach can help guide persons at risk for HIV exposure to decide on the best choice of pre-exposure prophylaxis (PrEP) regimens for them, stifling the noise generated by direct-to-consumer advertising, an infectious disease specialist recommends.

The decision for patients whether to start or remain on the PrEP combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC; Truvada and generic) or on tenofovir alafenamide (TAF) plus FTC (Descovy) is made more fraught by confusion regarding the use of the newer and allegedly safer TAF prodrug of tenofovir in HIV treatment regimens, said Oni Blackstock, MD, founder and executive director of Health Justice and an attending physician in the division of infectious diseases at Harlem Hospital, New York.

“There have been commercials on TV as well as on social media around class-action lawsuits against [Truvada maker] Gilead,” she said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases, held virtually this year.

“These lawsuits focus on TDF for HIV treatment, but they have sown a great deal of confusion about TDF versus TAF for PrEP among potential and actual PrEP users,” she added.

Dr. Blackstock described her approach to shared decision-making regarding TDF/FTC versus TAF/FTC, and to helping patients understand the relative benefits and risks of each formulation.

In January of 2020, Dr. Blackstock, who was then assistant commissioner of the HIV bureau of the New York City Department of Health and Mental Hygiene, issued with other Bureau members a “Dear colleague” letter stating why they believed that TDF/FTC should remain the first-line regimen for PrEP.

That opinion, she said, was bolstered by an editorial published in February 2020 by Douglas E. Krakower, MD, from Beth Israel Deaconess Medical Center in Boston, and colleagues, which questioned the rush to shift from TDF to TAF in HIV treatment, and cautioned against the same approach to PrEP.

“Despite evidence that TAF/FTC would not be cost-effective, compared with generic TDF/FTC , the newer regimen quickly and irrevocably displaced TDF/FTC for HIV treatment in the U.S. A similar shift for PrEP – especially for populations in which TAF/FTC is untested – would be premature, costly, and counterproductive for population impact,” Krakower et al. wrote.
 

Shared decision-making

Clinicians can help patients who may be a candidate for either PrEP regimen by engaging them in shared decision-making.

“The clinician provides information in this case about a prevention strategy, options, benefits and risks, alternatives, and the patient provides their preferences and values, and together the clinician and patient make a decision,” Dr. Blackstock said.

The process differs from the model of informed decision-making, where the clinician gives the patient the information and the patient comes to a decision, or the old, “paternalistic” model in which the clinician gives information and makes recommendations to the patient.

“Shared decision-making has been studied extensively and has been shown to improve patient satisfaction, patient communication, and also potentially reducing health inequities that we see,” she said.

The model for shared decision-making for clinical practice includes three distinct portions: a choice talk, option talk, and decision talk.
 

Choice

To begin the discussion, the physician informs the patients of the availability of choices and justifies them, saying, for example, “there is good information about how these two PrEP options differ that I’d like to discuss with you,” and “the two PrEP options have different side effects … some will matter more to you than other people.”

At this stage the clinician should defer closure by offering a more detailed discussion of the choices.
 

Option

Here the clinician solicits information about what the patient has heard or read about PrEP, describes each option in practical terms, and points out where the two regimens differ, being specific about the pros and cons of each (for example, potential bone mineral density loss or renal complications with TDF, and potential weight gain with subsequent metabolic and cardiovascular consequences with TAF).

The TDF versus TAF-based PrEP discussion could also focus on what’s known about the comparative effectiveness of each regimen.

For example, TDF/FTC has been shown to be about 99% effective at preventing infection in men who have sex with men and in transgender women, also about 99% effective in heterosexual women and men, and 74%-84% effective in persons who inject drugs.

In contrast, TAF/FTC has been shown to be about 99% effective in men who have sex with men and transgender women, but it’s efficacy in the other two categories is unknown, Dr. Blackstock said.

The option discussion should include a comparison of the evidence base for each regimen, including the real-world experience with TDF/FTC since 2012, and much more limited experience with TAF/FTC.

Discussing relative costs, although the wholesale costs of the regimens are similar, there is now a generic version of TDF/FTC made by Teva Pharmaceuticals that sells for about $400 less per month than the brand name, which might make the option more acceptable to health insurers.
 

Decision

The decision talk is about considering the patients preferences and deciding with them what is best.

The clinician could say, for example: “What, from your point of view, matters most to you?”

The clinician should also be willing to allow the patient to defer a decision or to guide them depending on their stated wish, asking something like: “Are you ready to decide, or do you want more time? Do you have more questions? Are there more things we should discuss?

Offering the patient a chance to review the decision can also be a good way to arrive at closure, Dr. Blackstock said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Blackstock presented her talk, said that he also uses a similar approach to the PrEP discussion.

“I use a very patient-centered approach of providing information and talking through the data that are available,” he said.

“I will say that, as patients come to me talking about the transition from TDF to TAF for pre-exposure prophylaxis, I am very clear with them about the limited benefit or no benefit that I see with TAF for pre-exposure prophylaxis, and all of my patients have remained on TDF for pre-exposure prophylaxis,” he added.

No funding source for the presentation was reported. Dr. Blackstock and Dr. Goldstein reported having no conflicts of interest to disclose.

A patient-centered approach can help guide persons at risk for HIV exposure to decide on the best choice of pre-exposure prophylaxis (PrEP) regimens for them, stifling the noise generated by direct-to-consumer advertising, an infectious disease specialist recommends.

The decision for patients whether to start or remain on the PrEP combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC; Truvada and generic) or on tenofovir alafenamide (TAF) plus FTC (Descovy) is made more fraught by confusion regarding the use of the newer and allegedly safer TAF prodrug of tenofovir in HIV treatment regimens, said Oni Blackstock, MD, founder and executive director of Health Justice and an attending physician in the division of infectious diseases at Harlem Hospital, New York.

“There have been commercials on TV as well as on social media around class-action lawsuits against [Truvada maker] Gilead,” she said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases, held virtually this year.

“These lawsuits focus on TDF for HIV treatment, but they have sown a great deal of confusion about TDF versus TAF for PrEP among potential and actual PrEP users,” she added.

Dr. Blackstock described her approach to shared decision-making regarding TDF/FTC versus TAF/FTC, and to helping patients understand the relative benefits and risks of each formulation.

In January of 2020, Dr. Blackstock, who was then assistant commissioner of the HIV bureau of the New York City Department of Health and Mental Hygiene, issued with other Bureau members a “Dear colleague” letter stating why they believed that TDF/FTC should remain the first-line regimen for PrEP.

That opinion, she said, was bolstered by an editorial published in February 2020 by Douglas E. Krakower, MD, from Beth Israel Deaconess Medical Center in Boston, and colleagues, which questioned the rush to shift from TDF to TAF in HIV treatment, and cautioned against the same approach to PrEP.

“Despite evidence that TAF/FTC would not be cost-effective, compared with generic TDF/FTC , the newer regimen quickly and irrevocably displaced TDF/FTC for HIV treatment in the U.S. A similar shift for PrEP – especially for populations in which TAF/FTC is untested – would be premature, costly, and counterproductive for population impact,” Krakower et al. wrote.
 

Shared decision-making

Clinicians can help patients who may be a candidate for either PrEP regimen by engaging them in shared decision-making.

“The clinician provides information in this case about a prevention strategy, options, benefits and risks, alternatives, and the patient provides their preferences and values, and together the clinician and patient make a decision,” Dr. Blackstock said.

The process differs from the model of informed decision-making, where the clinician gives the patient the information and the patient comes to a decision, or the old, “paternalistic” model in which the clinician gives information and makes recommendations to the patient.

“Shared decision-making has been studied extensively and has been shown to improve patient satisfaction, patient communication, and also potentially reducing health inequities that we see,” she said.

The model for shared decision-making for clinical practice includes three distinct portions: a choice talk, option talk, and decision talk.
 

Choice

To begin the discussion, the physician informs the patients of the availability of choices and justifies them, saying, for example, “there is good information about how these two PrEP options differ that I’d like to discuss with you,” and “the two PrEP options have different side effects … some will matter more to you than other people.”

At this stage the clinician should defer closure by offering a more detailed discussion of the choices.
 

Option

Here the clinician solicits information about what the patient has heard or read about PrEP, describes each option in practical terms, and points out where the two regimens differ, being specific about the pros and cons of each (for example, potential bone mineral density loss or renal complications with TDF, and potential weight gain with subsequent metabolic and cardiovascular consequences with TAF).

The TDF versus TAF-based PrEP discussion could also focus on what’s known about the comparative effectiveness of each regimen.

For example, TDF/FTC has been shown to be about 99% effective at preventing infection in men who have sex with men and in transgender women, also about 99% effective in heterosexual women and men, and 74%-84% effective in persons who inject drugs.

In contrast, TAF/FTC has been shown to be about 99% effective in men who have sex with men and transgender women, but it’s efficacy in the other two categories is unknown, Dr. Blackstock said.

The option discussion should include a comparison of the evidence base for each regimen, including the real-world experience with TDF/FTC since 2012, and much more limited experience with TAF/FTC.

Discussing relative costs, although the wholesale costs of the regimens are similar, there is now a generic version of TDF/FTC made by Teva Pharmaceuticals that sells for about $400 less per month than the brand name, which might make the option more acceptable to health insurers.
 

Decision

The decision talk is about considering the patients preferences and deciding with them what is best.

The clinician could say, for example: “What, from your point of view, matters most to you?”

The clinician should also be willing to allow the patient to defer a decision or to guide them depending on their stated wish, asking something like: “Are you ready to decide, or do you want more time? Do you have more questions? Are there more things we should discuss?

Offering the patient a chance to review the decision can also be a good way to arrive at closure, Dr. Blackstock said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Blackstock presented her talk, said that he also uses a similar approach to the PrEP discussion.

“I use a very patient-centered approach of providing information and talking through the data that are available,” he said.

“I will say that, as patients come to me talking about the transition from TDF to TAF for pre-exposure prophylaxis, I am very clear with them about the limited benefit or no benefit that I see with TAF for pre-exposure prophylaxis, and all of my patients have remained on TDF for pre-exposure prophylaxis,” he added.

No funding source for the presentation was reported. Dr. Blackstock and Dr. Goldstein reported having no conflicts of interest to disclose.

A patient-centered approach can help guide persons at risk for HIV exposure to decide on the best choice of pre-exposure prophylaxis (PrEP) regimens for them, stifling the noise generated by direct-to-consumer advertising, an infectious disease specialist recommends.

The decision for patients whether to start or remain on the PrEP combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC; Truvada and generic) or on tenofovir alafenamide (TAF) plus FTC (Descovy) is made more fraught by confusion regarding the use of the newer and allegedly safer TAF prodrug of tenofovir in HIV treatment regimens, said Oni Blackstock, MD, founder and executive director of Health Justice and an attending physician in the division of infectious diseases at Harlem Hospital, New York.

“There have been commercials on TV as well as on social media around class-action lawsuits against [Truvada maker] Gilead,” she said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases, held virtually this year.

“These lawsuits focus on TDF for HIV treatment, but they have sown a great deal of confusion about TDF versus TAF for PrEP among potential and actual PrEP users,” she added.

Dr. Blackstock described her approach to shared decision-making regarding TDF/FTC versus TAF/FTC, and to helping patients understand the relative benefits and risks of each formulation.

In January of 2020, Dr. Blackstock, who was then assistant commissioner of the HIV bureau of the New York City Department of Health and Mental Hygiene, issued with other Bureau members a “Dear colleague” letter stating why they believed that TDF/FTC should remain the first-line regimen for PrEP.

That opinion, she said, was bolstered by an editorial published in February 2020 by Douglas E. Krakower, MD, from Beth Israel Deaconess Medical Center in Boston, and colleagues, which questioned the rush to shift from TDF to TAF in HIV treatment, and cautioned against the same approach to PrEP.

“Despite evidence that TAF/FTC would not be cost-effective, compared with generic TDF/FTC , the newer regimen quickly and irrevocably displaced TDF/FTC for HIV treatment in the U.S. A similar shift for PrEP – especially for populations in which TAF/FTC is untested – would be premature, costly, and counterproductive for population impact,” Krakower et al. wrote.
 

Shared decision-making

Clinicians can help patients who may be a candidate for either PrEP regimen by engaging them in shared decision-making.

“The clinician provides information in this case about a prevention strategy, options, benefits and risks, alternatives, and the patient provides their preferences and values, and together the clinician and patient make a decision,” Dr. Blackstock said.

The process differs from the model of informed decision-making, where the clinician gives the patient the information and the patient comes to a decision, or the old, “paternalistic” model in which the clinician gives information and makes recommendations to the patient.

“Shared decision-making has been studied extensively and has been shown to improve patient satisfaction, patient communication, and also potentially reducing health inequities that we see,” she said.

The model for shared decision-making for clinical practice includes three distinct portions: a choice talk, option talk, and decision talk.