Infectious Diseases

Mirroring the opioid crisis, maternal and newborn hepatitis C infections (HCV) more than doubled in the United States between 2009 and 2019, with disproportionate increases in people of White, American Indian, and Alaska Native race, especially those with less education, according to a cross-sectional study published in JAMA Health Forum. However, the level of risk within these populations was mitigated in counties with higher employment, reported Stephen W. Patrick, MD, of Vanderbilt University, in Nashville, Tenn., and coauthors.

“As we develop public health approaches to prevent HCV infections, connect to treatment, and monitor exposed infants, understanding these factors can be of critical importance to tailoring interventions,” Dr. Patrick said in an interview. “HCV is one more complication of the opioid crisis,” he added. “These data also enable us to step back a bit from HCV and look at the landscape of how the opioid crisis continues to grow in complexity and scope. Throughout the opioid crisis we have often failed to recognize and address the unique needs of pregnant people and infants.”

The study authors used data from the National Center for Health Statistics at the Centers for Disease Control and Prevention, and from the Area Health Resource File to examine maternal-infant HCV infection among all U.S. births between 2009 and 2019. The researchers also examined community-level risk factors including rurality, employment, and access to medical care.

In counties reporting HCV, there were 39,380,122 people who had live births, of whom 138,343 (0.4%) were diagnosed with HCV. The overall rate of maternal HCV infection increased from 1.8 to 5.1 per 1,000 live births between 2009 and 2019.

Infection rates were highest in American Indian/Alaska Native (AI/AN) and White people (adjusted odds ratio [aOR] 7.94 and 7.37, respectively) compared with Black people. They were higher among individuals without a 4-year degree compared to those with higher education (aOR, 3.19).

Among these groups considered to be at higher risk for HCV infection, high employment rates somewhat mitigated the risk. Specifically, in counties in the 10th percentile of employment, the predicted probability of HCV increased from 0.16% to 1.37%, between 2009 and 2019, whereas in counties at the 90th percentile of employment, the predicted probability remained similar, at 0.36% in 2009 and 0.48% in 2019.

“With constrained national resources, understanding both individual and community-level factors associated with HCV infections in pregnant people could inform strategies to mitigate its spread, such as harm reduction efforts (e.g., syringe service programs), improving access to treatment for [opioid use disorder] or increasing the obstetrical workforce in high-risk communities, HCV testing strategies in pregnant people and people of childbearing age, and treatment with novel antiviral therapies,” wrote the authors.

In the time since the authors began the study, universal HCV screening for every pregnancy has been recommended by a number of groups, including the U.S. Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine (SMFM). However, Dr. Patrick says even though such recommendations are now adopted, it will be some time before they are fully operational, making knowledge of HCV risk factors important for obstetricians as well as pediatricians and family physicians. “We don’t know how if hospitals and clinicians have started universal screening for HCV and even when it is completely adopted, understanding individual and community-level factors associated with HCV in pregnant people is still of critical importance,” he explained. “In some of our previous work we have found that non-White HCV-exposed infants are less likely to be tested for HCV than are White infants, even after accounting for multiple individual and hospital-level factors. The pattern we are seeing in our research and in research in other groups is one of unequal treatment of pregnant people with substance use disorder in terms of being given evidence-based treatments, being tested for HCV, and even in child welfare outcomes like foster placement. It is important to know these issues are occurring, but we need specific equitable approaches to ensuring optimal outcomes for all families.

Jeffrey A. Kuller, MD, one of the authors of the SMFM’s new recommendations for universal HCV screening in pregnancy, agreed that until universal screening is widely adopted, awareness of maternal HCV risk factors is important, “to better determine who is at highest risk for hep C, barriers to care, and patients to better target.” This information also affects procedure at the time of delivery, added Dr. Kuller, professor of obstetrics and gynecology in the division of maternal-fetal medicine at Duke University, Durham, N.C. “We do not perform C-sections for the presence of hep C,” he told this publication. However, in labor, “we try to avoid internal fetal monitoring when possible, and early artificial rupture of membranes when possible, and avoid the use of routine episiotomy,” he said. “Hep C–positive patients should also be assessed for other sexually transmitted diseases including HIV, syphilis, gonorrhea, chlamydia, and hep B. “Although we do not typically treat hep C pharmacologically during pregnancy, we try to get the patient placed with a hepatologist for long-term management.”

The study has important implications for pediatric patients, added Audrey R. Lloyd, MD, a med-peds infectious disease fellow who is studying HCV in pregnancy at the University of Alabama at Birmingham. “In the setting of maternal HCV viremia, maternal-fetal transmission occurs in around 6% of exposed infants and around 10% if there is maternal HIV-HCV coinfection,” she said in an interview. “With the increasing rates of HCV in pregnant women described by Dr. Patrick et al., HCV infections among infants will also rise. Even when maternal HCV infection is documented, we often do not do a good job screening the infants for infection and linking them to treatment. This new data makes me worried we may see more complications of pediatric HCV infection in the future,” she added. She explained that safe and effective treatments for HCV infection are approved down to 3 years of age, but patients must first be diagnosed to receive treatment. 

From whichever angle you approach it, tackling both the opioid epidemic and HCV infection in pregnancy will inevitably end up helping both parts of the mother-infant dyad, said Dr. Patrick. “Not too long ago I was caring for an opioid-exposed infant at the hospital where I practice who had transferred in from another center hours away. The mother had not been tested for HCV, so I tested the infant for HCV antibodies which were positive. Imagine that, determining a mother is HCV positive by testing the infant. There are so many layers of systems that should be fixed to make this not happen. And what are the chances the mother, after she found out, was able to access treatment for HCV? What about the infant being tested? The systems are just fragmented and we need to do better.”

The study was funded by the National Institute on Drug Abuse of the National Institutes of Health. Neither Dr. Patrick, Dr. Kuller, nor Dr. Lloyd reported any conflicts of interest.

Mirroring the opioid crisis, maternal and newborn hepatitis C infections (HCV) more than doubled in the United States between 2009 and 2019, with disproportionate increases in people of White, American Indian, and Alaska Native race, especially those with less education, according to a cross-sectional study published in JAMA Health Forum. However, the level of risk within these populations was mitigated in counties with higher employment, reported Stephen W. Patrick, MD, of Vanderbilt University, in Nashville, Tenn., and coauthors.

“As we develop public health approaches to prevent HCV infections, connect to treatment, and monitor exposed infants, understanding these factors can be of critical importance to tailoring interventions,” Dr. Patrick said in an interview. “HCV is one more complication of the opioid crisis,” he added. “These data also enable us to step back a bit from HCV and look at the landscape of how the opioid crisis continues to grow in complexity and scope. Throughout the opioid crisis we have often failed to recognize and address the unique needs of pregnant people and infants.”

The study authors used data from the National Center for Health Statistics at the Centers for Disease Control and Prevention, and from the Area Health Resource File to examine maternal-infant HCV infection among all U.S. births between 2009 and 2019. The researchers also examined community-level risk factors including rurality, employment, and access to medical care.

In counties reporting HCV, there were 39,380,122 people who had live births, of whom 138,343 (0.4%) were diagnosed with HCV. The overall rate of maternal HCV infection increased from 1.8 to 5.1 per 1,000 live births between 2009 and 2019.

Infection rates were highest in American Indian/Alaska Native (AI/AN) and White people (adjusted odds ratio [aOR] 7.94 and 7.37, respectively) compared with Black people. They were higher among individuals without a 4-year degree compared to those with higher education (aOR, 3.19).

Among these groups considered to be at higher risk for HCV infection, high employment rates somewhat mitigated the risk. Specifically, in counties in the 10th percentile of employment, the predicted probability of HCV increased from 0.16% to 1.37%, between 2009 and 2019, whereas in counties at the 90th percentile of employment, the predicted probability remained similar, at 0.36% in 2009 and 0.48% in 2019.

“With constrained national resources, understanding both individual and community-level factors associated with HCV infections in pregnant people could inform strategies to mitigate its spread, such as harm reduction efforts (e.g., syringe service programs), improving access to treatment for [opioid use disorder] or increasing the obstetrical workforce in high-risk communities, HCV testing strategies in pregnant people and people of childbearing age, and treatment with novel antiviral therapies,” wrote the authors.

In the time since the authors began the study, universal HCV screening for every pregnancy has been recommended by a number of groups, including the U.S. Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine (SMFM). However, Dr. Patrick says even though such recommendations are now adopted, it will be some time before they are fully operational, making knowledge of HCV risk factors important for obstetricians as well as pediatricians and family physicians. “We don’t know how if hospitals and clinicians have started universal screening for HCV and even when it is completely adopted, understanding individual and community-level factors associated with HCV in pregnant people is still of critical importance,” he explained. “In some of our previous work we have found that non-White HCV-exposed infants are less likely to be tested for HCV than are White infants, even after accounting for multiple individual and hospital-level factors. The pattern we are seeing in our research and in research in other groups is one of unequal treatment of pregnant people with substance use disorder in terms of being given evidence-based treatments, being tested for HCV, and even in child welfare outcomes like foster placement. It is important to know these issues are occurring, but we need specific equitable approaches to ensuring optimal outcomes for all families.

Jeffrey A. Kuller, MD, one of the authors of the SMFM’s new recommendations for universal HCV screening in pregnancy, agreed that until universal screening is widely adopted, awareness of maternal HCV risk factors is important, “to better determine who is at highest risk for hep C, barriers to care, and patients to better target.” This information also affects procedure at the time of delivery, added Dr. Kuller, professor of obstetrics and gynecology in the division of maternal-fetal medicine at Duke University, Durham, N.C. “We do not perform C-sections for the presence of hep C,” he told this publication. However, in labor, “we try to avoid internal fetal monitoring when possible, and early artificial rupture of membranes when possible, and avoid the use of routine episiotomy,” he said. “Hep C–positive patients should also be assessed for other sexually transmitted diseases including HIV, syphilis, gonorrhea, chlamydia, and hep B. “Although we do not typically treat hep C pharmacologically during pregnancy, we try to get the patient placed with a hepatologist for long-term management.”

The study has important implications for pediatric patients, added Audrey R. Lloyd, MD, a med-peds infectious disease fellow who is studying HCV in pregnancy at the University of Alabama at Birmingham. “In the setting of maternal HCV viremia, maternal-fetal transmission occurs in around 6% of exposed infants and around 10% if there is maternal HIV-HCV coinfection,” she said in an interview. “With the increasing rates of HCV in pregnant women described by Dr. Patrick et al., HCV infections among infants will also rise. Even when maternal HCV infection is documented, we often do not do a good job screening the infants for infection and linking them to treatment. This new data makes me worried we may see more complications of pediatric HCV infection in the future,” she added. She explained that safe and effective treatments for HCV infection are approved down to 3 years of age, but patients must first be diagnosed to receive treatment. 

From whichever angle you approach it, tackling both the opioid epidemic and HCV infection in pregnancy will inevitably end up helping both parts of the mother-infant dyad, said Dr. Patrick. “Not too long ago I was caring for an opioid-exposed infant at the hospital where I practice who had transferred in from another center hours away. The mother had not been tested for HCV, so I tested the infant for HCV antibodies which were positive. Imagine that, determining a mother is HCV positive by testing the infant. There are so many layers of systems that should be fixed to make this not happen. And what are the chances the mother, after she found out, was able to access treatment for HCV? What about the infant being tested? The systems are just fragmented and we need to do better.”

The study was funded by the National Institute on Drug Abuse of the National Institutes of Health. Neither Dr. Patrick, Dr. Kuller, nor Dr. Lloyd reported any conflicts of interest.

Mirroring the opioid crisis, maternal and newborn hepatitis C infections (HCV) more than doubled in the United States between 2009 and 2019, with disproportionate increases in people of White, American Indian, and Alaska Native race, especially those with less education, according to a cross-sectional study published in JAMA Health Forum. However, the level of risk within these populations was mitigated in counties with higher employment, reported Stephen W. Patrick, MD, of Vanderbilt University, in Nashville, Tenn., and coauthors.

“As we develop public health approaches to prevent HCV infections, connect to treatment, and monitor exposed infants, understanding these factors can be of critical importance to tailoring interventions,” Dr. Patrick said in an interview. “HCV is one more complication of the opioid crisis,” he added. “These data also enable us to step back a bit from HCV and look at the landscape of how the opioid crisis continues to grow in complexity and scope. Throughout the opioid crisis we have often failed to recognize and address the unique needs of pregnant people and infants.”

The study authors used data from the National Center for Health Statistics at the Centers for Disease Control and Prevention, and from the Area Health Resource File to examine maternal-infant HCV infection among all U.S. births between 2009 and 2019. The researchers also examined community-level risk factors including rurality, employment, and access to medical care.

In counties reporting HCV, there were 39,380,122 people who had live births, of whom 138,343 (0.4%) were diagnosed with HCV. The overall rate of maternal HCV infection increased from 1.8 to 5.1 per 1,000 live births between 2009 and 2019.

Infection rates were highest in American Indian/Alaska Native (AI/AN) and White people (adjusted odds ratio [aOR] 7.94 and 7.37, respectively) compared with Black people. They were higher among individuals without a 4-year degree compared to those with higher education (aOR, 3.19).

Among these groups considered to be at higher risk for HCV infection, high employment rates somewhat mitigated the risk. Specifically, in counties in the 10th percentile of employment, the predicted probability of HCV increased from 0.16% to 1.37%, between 2009 and 2019, whereas in counties at the 90th percentile of employment, the predicted probability remained similar, at 0.36% in 2009 and 0.48% in 2019.

“With constrained national resources, understanding both individual and community-level factors associated with HCV infections in pregnant people could inform strategies to mitigate its spread, such as harm reduction efforts (e.g., syringe service programs), improving access to treatment for [opioid use disorder] or increasing the obstetrical workforce in high-risk communities, HCV testing strategies in pregnant people and people of childbearing age, and treatment with novel antiviral therapies,” wrote the authors.

In the time since the authors began the study, universal HCV screening for every pregnancy has been recommended by a number of groups, including the U.S. Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine (SMFM). However, Dr. Patrick says even though such recommendations are now adopted, it will be some time before they are fully operational, making knowledge of HCV risk factors important for obstetricians as well as pediatricians and family physicians. “We don’t know how if hospitals and clinicians have started universal screening for HCV and even when it is completely adopted, understanding individual and community-level factors associated with HCV in pregnant people is still of critical importance,” he explained. “In some of our previous work we have found that non-White HCV-exposed infants are less likely to be tested for HCV than are White infants, even after accounting for multiple individual and hospital-level factors. The pattern we are seeing in our research and in research in other groups is one of unequal treatment of pregnant people with substance use disorder in terms of being given evidence-based treatments, being tested for HCV, and even in child welfare outcomes like foster placement. It is important to know these issues are occurring, but we need specific equitable approaches to ensuring optimal outcomes for all families.

Jeffrey A. Kuller, MD, one of the authors of the SMFM’s new recommendations for universal HCV screening in pregnancy, agreed that until universal screening is widely adopted, awareness of maternal HCV risk factors is important, “to better determine who is at highest risk for hep C, barriers to care, and patients to better target.” This information also affects procedure at the time of delivery, added Dr. Kuller, professor of obstetrics and gynecology in the division of maternal-fetal medicine at Duke University, Durham, N.C. “We do not perform C-sections for the presence of hep C,” he told this publication. However, in labor, “we try to avoid internal fetal monitoring when possible, and early artificial rupture of membranes when possible, and avoid the use of routine episiotomy,” he said. “Hep C–positive patients should also be assessed for other sexually transmitted diseases including HIV, syphilis, gonorrhea, chlamydia, and hep B. “Although we do not typically treat hep C pharmacologically during pregnancy, we try to get the patient placed with a hepatologist for long-term management.”

The study has important implications for pediatric patients, added Audrey R. Lloyd, MD, a med-peds infectious disease fellow who is studying HCV in pregnancy at the University of Alabama at Birmingham. “In the setting of maternal HCV viremia, maternal-fetal transmission occurs in around 6% of exposed infants and around 10% if there is maternal HIV-HCV coinfection,” she said in an interview. “With the increasing rates of HCV in pregnant women described by Dr. Patrick et al., HCV infections among infants will also rise. Even when maternal HCV infection is documented, we often do not do a good job screening the infants for infection and linking them to treatment. This new data makes me worried we may see more complications of pediatric HCV infection in the future,” she added. She explained that safe and effective treatments for HCV infection are approved down to 3 years of age, but patients must first be diagnosed to receive treatment. 

From whichever angle you approach it, tackling both the opioid epidemic and HCV infection in pregnancy will inevitably end up helping both parts of the mother-infant dyad, said Dr. Patrick. “Not too long ago I was caring for an opioid-exposed infant at the hospital where I practice who had transferred in from another center hours away. The mother had not been tested for HCV, so I tested the infant for HCV antibodies which were positive. Imagine that, determining a mother is HCV positive by testing the infant. There are so many layers of systems that should be fixed to make this not happen. And what are the chances the mother, after she found out, was able to access treatment for HCV? What about the infant being tested? The systems are just fragmented and we need to do better.”

The study was funded by the National Institute on Drug Abuse of the National Institutes of Health. Neither Dr. Patrick, Dr. Kuller, nor Dr. Lloyd reported any conflicts of interest.

With children aged 5-11 years about to enter the battle-of-the-COVID-vaccine phase of the war on COVID, there are many questions. MDedge takes a look at one: How long will it take to get 5- to 11-year-olds vaccinated?

Previous experience may provide some guidance. The vaccine was approved by the Centers for Disease Control and Prevention for the closest group in age, 12- to 15-year-olds, on May 12, 2021, and by May 17, over 750,000 children, or 5% of the demographic category, had received at least one dose. By Sept. 9 – 109 days later – 50% of all 15.2 million children aged 12-15 had received at least one dose of the COVID-19 vaccine, according to data from the CDC.

(Use of the 5% figure acknowledges the uneven start after approval – the vaccine became available to different age groups at different times, even though it had been approved for all adults aged 18 years and older.)

The 16- to 17-year-olds, despite being a smaller group of less than 7.6 million individuals, took 120 days to go from 5% to 50% coverage. For those aged 18-24 years, the corresponding time was 132 days, while the 24- to 36-year-olds took longer than any other age group, 135 days, to reach the 50%-with-at-least-one-dose milestone. The time, in turn, decreased for each group as age increased, with those aged 75 and older taking just 41 days to get at least one dose in 50% of individuals, the CDC data show.

That trend also applies to full vaccination, for the most part. The oldest group, 75 and older, had the shortest time to 50% being fully vaccinated at 69 days, and the 25- to 39-year-olds had the longest time at 206 days, with the length rising as age decreased and dropping for groups younger than 25-39. Except for the 12- to 15-year-olds. It has been 160 days (as of Nov. 2) since the 5% mark was reached on May 17, but only 47.4% of the group is fully vaccinated, making it unlikely that the 50% mark will be reached earlier than the 169 days it took the 16- to 17-year-olds.

So where does that put the 5- to 11-year-olds?

The White House said on Nov. 1 that vaccinations could start the first week of November, pending approval from the CDC’s Advisory Committee on Immunization Practices, which meets on Nov. 2. “This is an important step forward in our nation’s fight against the virus,” Jeff Zients, the White House COVID-19 Response Coordinator, said in a briefing. “As we await the CDC decision, we are not waiting on the operations and logistics. In fact, we’ve been preparing for weeks.”

Availability, of course, is not the only factor involved. In a survey conducted Oct. 14-24, the Kaiser Family Foundation found that only 27% of parents of children aged 5-11 years are planning to have them vaccinated against COVID-19 “right away” once the vaccine is available, and that 33% would “wait and see” how the vaccine works.

“Parents of 5-11 year-olds cite a range of concerns when it comes to vaccinating their children for COVID-19, with safety issues topping off the list,” and “two-thirds say they are concerned the vaccine may negatively impact their child’s fertility in the future,” Kaiser said.

rfranki@mdedge.com

With children aged 5-11 years about to enter the battle-of-the-COVID-vaccine phase of the war on COVID, there are many questions. MDedge takes a look at one: How long will it take to get 5- to 11-year-olds vaccinated?

Previous experience may provide some guidance. The vaccine was approved by the Centers for Disease Control and Prevention for the closest group in age, 12- to 15-year-olds, on May 12, 2021, and by May 17, over 750,000 children, or 5% of the demographic category, had received at least one dose. By Sept. 9 – 109 days later – 50% of all 15.2 million children aged 12-15 had received at least one dose of the COVID-19 vaccine, according to data from the CDC.

(Use of the 5% figure acknowledges the uneven start after approval – the vaccine became available to different age groups at different times, even though it had been approved for all adults aged 18 years and older.)

The 16- to 17-year-olds, despite being a smaller group of less than 7.6 million individuals, took 120 days to go from 5% to 50% coverage. For those aged 18-24 years, the corresponding time was 132 days, while the 24- to 36-year-olds took longer than any other age group, 135 days, to reach the 50%-with-at-least-one-dose milestone. The time, in turn, decreased for each group as age increased, with those aged 75 and older taking just 41 days to get at least one dose in 50% of individuals, the CDC data show.

That trend also applies to full vaccination, for the most part. The oldest group, 75 and older, had the shortest time to 50% being fully vaccinated at 69 days, and the 25- to 39-year-olds had the longest time at 206 days, with the length rising as age decreased and dropping for groups younger than 25-39. Except for the 12- to 15-year-olds. It has been 160 days (as of Nov. 2) since the 5% mark was reached on May 17, but only 47.4% of the group is fully vaccinated, making it unlikely that the 50% mark will be reached earlier than the 169 days it took the 16- to 17-year-olds.

So where does that put the 5- to 11-year-olds?

The White House said on Nov. 1 that vaccinations could start the first week of November, pending approval from the CDC’s Advisory Committee on Immunization Practices, which meets on Nov. 2. “This is an important step forward in our nation’s fight against the virus,” Jeff Zients, the White House COVID-19 Response Coordinator, said in a briefing. “As we await the CDC decision, we are not waiting on the operations and logistics. In fact, we’ve been preparing for weeks.”

Availability, of course, is not the only factor involved. In a survey conducted Oct. 14-24, the Kaiser Family Foundation found that only 27% of parents of children aged 5-11 years are planning to have them vaccinated against COVID-19 “right away” once the vaccine is available, and that 33% would “wait and see” how the vaccine works.

“Parents of 5-11 year-olds cite a range of concerns when it comes to vaccinating their children for COVID-19, with safety issues topping off the list,” and “two-thirds say they are concerned the vaccine may negatively impact their child’s fertility in the future,” Kaiser said.

rfranki@mdedge.com

With children aged 5-11 years about to enter the battle-of-the-COVID-vaccine phase of the war on COVID, there are many questions. MDedge takes a look at one: How long will it take to get 5- to 11-year-olds vaccinated?

Previous experience may provide some guidance. The vaccine was approved by the Centers for Disease Control and Prevention for the closest group in age, 12- to 15-year-olds, on May 12, 2021, and by May 17, over 750,000 children, or 5% of the demographic category, had received at least one dose. By Sept. 9 – 109 days later – 50% of all 15.2 million children aged 12-15 had received at least one dose of the COVID-19 vaccine, according to data from the CDC.

(Use of the 5% figure acknowledges the uneven start after approval – the vaccine became available to different age groups at different times, even though it had been approved for all adults aged 18 years and older.)

The 16- to 17-year-olds, despite being a smaller group of less than 7.6 million individuals, took 120 days to go from 5% to 50% coverage. For those aged 18-24 years, the corresponding time was 132 days, while the 24- to 36-year-olds took longer than any other age group, 135 days, to reach the 50%-with-at-least-one-dose milestone. The time, in turn, decreased for each group as age increased, with those aged 75 and older taking just 41 days to get at least one dose in 50% of individuals, the CDC data show.

That trend also applies to full vaccination, for the most part. The oldest group, 75 and older, had the shortest time to 50% being fully vaccinated at 69 days, and the 25- to 39-year-olds had the longest time at 206 days, with the length rising as age decreased and dropping for groups younger than 25-39. Except for the 12- to 15-year-olds. It has been 160 days (as of Nov. 2) since the 5% mark was reached on May 17, but only 47.4% of the group is fully vaccinated, making it unlikely that the 50% mark will be reached earlier than the 169 days it took the 16- to 17-year-olds.

So where does that put the 5- to 11-year-olds?

The White House said on Nov. 1 that vaccinations could start the first week of November, pending approval from the CDC’s Advisory Committee on Immunization Practices, which meets on Nov. 2. “This is an important step forward in our nation’s fight against the virus,” Jeff Zients, the White House COVID-19 Response Coordinator, said in a briefing. “As we await the CDC decision, we are not waiting on the operations and logistics. In fact, we’ve been preparing for weeks.”

Availability, of course, is not the only factor involved. In a survey conducted Oct. 14-24, the Kaiser Family Foundation found that only 27% of parents of children aged 5-11 years are planning to have them vaccinated against COVID-19 “right away” once the vaccine is available, and that 33% would “wait and see” how the vaccine works.

“Parents of 5-11 year-olds cite a range of concerns when it comes to vaccinating their children for COVID-19, with safety issues topping off the list,” and “two-thirds say they are concerned the vaccine may negatively impact their child’s fertility in the future,” Kaiser said.

rfranki@mdedge.com

Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.

In a large case-control study, investigators found the odds of PD were elevated by approximately 90% for PD that occurred more than 15 years after influenza infection and by more than 70% for PD occurring more than 10 years after the flu.

“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.

The study was published online Oct. 25 in JAMA Neurology.

Ongoing debate

The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.

Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.

They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.

Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.

They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.

The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.

“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.

Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.

For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.

The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).

However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
 

Potential COVID-19–related PD surge?

In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.

Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.

Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.

“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.

An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.

“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.

It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.

“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.

As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.

However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.

Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
 

‘Exciting and important’ findings

Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.

However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.

The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.

Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”

The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.

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

Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.

In a large case-control study, investigators found the odds of PD were elevated by approximately 90% for PD that occurred more than 15 years after influenza infection and by more than 70% for PD occurring more than 10 years after the flu.

“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.

The study was published online Oct. 25 in JAMA Neurology.

Ongoing debate

The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.

Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.

They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.

Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.

They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.

The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.

“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.

Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.

For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.

The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).

However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
 

Potential COVID-19–related PD surge?

In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.

Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.

Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.

“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.

An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.

“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.

It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.

“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.

As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.

However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.

Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
 

‘Exciting and important’ findings

Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.

However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.

The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.

Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”

The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.

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

Influenza infection is linked to a subsequent diagnosis of Parkinson’s disease (PD) more than 10 years later, resurfacing a long-held debate about whether infection increases the risk for movement disorders over the long term.

In a large case-control study, investigators found the odds of PD were elevated by approximately 90% for PD that occurred more than 15 years after influenza infection and by more than 70% for PD occurring more than 10 years after the flu.

“This study is not definitive by any means, but it certainly suggests there are potential long-term consequences from influenza,” study investigator Noelle M. Cocoros, DSc, research scientist at Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, said in an interview.

The study was published online Oct. 25 in JAMA Neurology.

Ongoing debate

The debate about whether influenza is associated with PD has been going on as far back as the 1918 influenza pandemic, when experts documented parkinsonism in affected individuals.

Using data from the Danish patient registry, researchers identified 10,271 subjects diagnosed with PD during a 17-year period (2000-2016). Of these, 38.7% were female, and the mean age was 71.4 years.

They matched these subjects for age and sex to 51,355 controls without PD. Compared with controls, slightly fewer individuals with PD had chronic obstructive pulmonary disease (COPD) or emphysema, but there was a similar distribution of cardiovascular disease and various other conditions.

Researchers collected data on influenza diagnoses from inpatient and outpatient hospital clinics from 1977 to 2016. They plotted these by month and year on a graph, calculated the median number of diagnoses per month, and identified peaks as those with more than threefold the median.

They categorized cases in groups related to the time between the infection and PD: More than 10 years, 10-15 years, and more than 15 years.

The time lapse accounts for a rather long “run-up” to PD, said Dr. Cocoros. There’s a sometimes decades-long preclinical phase before patients develop typical motor signs and a prodromal phase where they may present with nonmotor symptoms such as sleep disorders and constipation.

“We expected there would be at least 10 years between any infection and PD if there was an association present,” said Dr. Cocoros.

Investigators found an association between influenza exposure and PD diagnosis “that held up over time,” she said.

For more than 10 years before PD, the likelihood of a diagnosis for the infected compared with the unexposed was increased 73% (odds ratio [OR] 1.73; 95% confidence interval, 1.11-2.71; P = .02) after adjustment for cardiovascular disease, diabetes, chronic obstructive pulmonary disease, emphysema, lung cancer, Crohn’s disease, and ulcerative colitis.

The odds increased with more time from infection. For more than 15 years, the adjusted OR was 1.91 (95% CI, 1.14 - 3.19; P =.01).

However, for the 10- to 15-year time frame, the point estimate was reduced and the CI nonsignificant (OR, 1.33; 95% CI, 0.54-3.27; P = .53). This “is a little hard to interpret,” but could be a result of the small numbers, exposure misclassification, or because “the longer time interval is what’s meaningful,” said Dr. Cocoros.
 

Potential COVID-19–related PD surge?

In a sensitivity analysis, researchers looked at peak infection activity. “We wanted to increase the likelihood of these diagnoses representing actual infection,” Dr. Cocoros noted.

Here, the OR was still elevated at more than 10 years, but the CI was quite wide and included 1 (OR, 1.52; 95% CI, 0.80-2.89; P = .21). “So the association holds up, but the estimates are quite unstable,” said Dr. Cocoros.

Researchers examined associations with numerous other infection types, but did not see the same trend over time. Some infections – for example, gastrointestinal infections and septicemia – were associated with PD within 5 years, but most associations appeared to be null after more than 10 years.

“There seemed to be associations earlier between the infection and PD, which we interpret to suggest there’s actually not a meaningful association,” said Dr. Cocoros.

An exception might be urinary tract infections (UTIs), where after 10 years, the adjusted OR was 1.19 (95% CI, 1.01-1.40). Research suggests patients with PD often have UTIs and neurogenic bladder.

“It’s possible that UTIs could be an early symptom of PD rather than a causative factor,” said Dr. Cocoros.

It’s unclear how influenza might lead to PD but it could be that the virus gets into the central nervous system, resulting in neuroinflammation. Cytokines generated in response to the influenza infection might damage the brain.

“The infection could be a ‘primer’ or an initial ‘hit’ to the system, maybe setting people up for PD,” said Dr. Cocoros.

As for the current COVID-19 pandemic, some experts are concerned about a potential surge in PD cases in decades to come, and are calling for prospective monitoring of patients with this infection, said Dr. Cocoros.

However, she noted that infections don’t account for all PD cases and that genetic and environmental factors also influence risk.

Many individuals who contract influenza don’t seek medical care or get tested, so it’s possible the study counted those who had the infection as unexposed. Another potential study limitation was that small numbers for some infections, for example, Helicobacter pylori and hepatitis C, limited the ability to interpret results.
 

‘Exciting and important’ findings

Commenting on the research for this news organization, Aparna Wagle Shukla, MD, professor, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, said the results amid the current pandemic are “exciting and important” and “have reinvigorated interest” in the role of infection in PD.

However, the study had some limitations, an important one being lack of accounting for confounding factors, including environmental factors, she said. Exposure to pesticides, living in a rural area, drinking well water, and having had a head injury may increase PD risk, whereas high intake of caffeine, nicotine, alcohol, and nonsteroidal anti-inflammatory drugs might lower the risk.

The researchers did not take into account exposure to multiple microbes or “infection burden,” said Dr. Wagle Shukla, who was not involved in the current study. In addition, as the data are from a single country with exposure to specific influenza strains, application of the findings elsewhere may be limited.

Dr. Wagle Shukla noted that a case-control design “isn’t ideal” from an epidemiological perspective. “Future studies should involve large cohorts followed longitudinally.”

The study was supported by grants from the Lundbeck Foundation and the Augustinus Foundation. Dr. Cocoros has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry. The full list can be found with the original article.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Clinicians are prescribing clarithromycin at high rates for Helicobacter pylori infections, despite increasing resistance to this antibiotic, researchers say.

In an analysis of 1 million U.S. prescriptions for H. pylori infections, 80% contained clarithromycin, said Carol Rockett, PharmD, associate vice president of RedHill Biopharma in Raleigh, N.C.

Dr. Rockett presented the findings at the annual meeting of the American College of Gastroenterology.

“Multiple talks [at the meeting] have suggested that the use of clarithromycin in H. pylori is obsolete,” she told this news organization. “Clarithromycin is particularly ineffective in people with a genetic variant that causes rapid metabolism.”

According to the 2017 ACG clinical guideline for treating H. pylori, patients diagnosed with this infection should be asked about their previous antibiotic exposure prior to treatment.

Additionally, clinicians should prescribe clarithromycin triple therapy with a proton pump inhibitor (PPI) and amoxicillin or metronidazole as a first-line treatment only in “regions where H. pylori clarithromycin resistance is known to be less than 15%” and in patients with no previous history of macrolide exposure.

The guideline puts bismuth quadruple therapy, consisting of a PPI, bismuth, tetracycline, and a nitroimidazole, at the top of its list of six alternative first-line therapies. However, three of the six alternatives include clarithromycin.
 

ERADICATE Hp and ERADICATE Hp2

To understand how U.S. physicians are treating patients with H. pylori, Dr. Rockett’s colleagues analyzed data from two phase 3 clinical trials of RedHill’s RHB-105 (Talicia): ERADICATE Hp and ERADICATE Hp2.

RHB-105 is an all-in‐one combination of omeprazole (40 mg), amoxicillin (1,000 mg), and rifabutin (50 mg) that the Food and Drug Administration approved for treatment of H pylori in 2019.

The researchers followed 38 subjects from ERADICATE Hp who remained positive for H. pylori after the study’s completion. A total of 33 had received a placebo in that trial, while the other 5 had received RHB-105.

The researchers obtained data on 31 of these patients. The overall cure rate was 61.3%. Of the 31 patients, 27 received a regimen including clarithromycin. Their cure rate was 59.3%.

Turning to ERADICATE Hp2, the researchers obtained data on 94 patients whose H. pylori infections persisted after the trial. Of those, 67 had received an active comparator (amoxicillin 250 mg and omeprazole 10 mg) and 27 had received RHB-105.

The overall cure rate was 56.2%. For the 48 subjects who received therapies including clarithromycin, the cure rate was 60.4%. For the 22 subjects who received a bismuth-based quadruple regimen, the cure rate was 45.4%.

In another analysis, the researchers crunched 12 months of numbers from IQVIA PharMetrics Plus medical and prescription claim database of over 1 million prescriptions for H. pylori. They found that 80% of the prescriptions made by gastroenterologists were for regimens containing clarithromycin. That proportion increased to 84% for physician assistants and internists, 85% for nurse practitioners, 86% for family practitioners, and 89% for general practitioners.

Finally, the researchers also analyzed patients for CYP2C19 gene status. They tested 65 subjects who received RHB-105 in ERADICATE Hp and all 445 subjects in ERADICATE Hp2. They found that 58.5% in ERADICATE Hp and 48.6% in ERADICATE Hp2 were normal metabolizers.

In 20 normal metabolizers who received clarithromycin, the drug eradicated the infection in 16 (80%). Out of 11 rapid metabolizers, clarithromycin eradicated the bacterium in 2 (18.2%). The difference was statistically significant (P = .0017).

“With clarithromycin, you can see that the efficacy is reduced in those patients who are rapid metabolizers,” Dr. Rockett said. “We didn’t see that with rifabutin [one of the drugs in RHB-105].”

Jared Magee, DO, MPH, a gastroenterology fellow at the Walter Reed National Military Medical Center in Bethesda, Md., said in treating H. pylori infections, he checks the patients’ medical records to see what antibiotics they have received in the past and generally begins treatment with the bismuth quadruple therapy.

“There is education needed to get the data out there that clarithromycin-based therapies may not be the right choice for patients,” he said. “There is a subset who will do well with it, but I think where we’re at now, with the frequency of macrolide prescriptions for other conditions, that clarithromycin is going to be a difficult therapy for a lot of people.”

Clinicians who are not gastroenterologists may not be aware of the guideline promulgated by the ACG, he pointed out.

Dr. Rockett is an employee of RedHill Biopharma. Dr. Magee has disclosed no relevant financial relationships. The study was funded by RedHill Biopharma.

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

Clinicians are prescribing clarithromycin at high rates for Helicobacter pylori infections, despite increasing resistance to this antibiotic, researchers say.

In an analysis of 1 million U.S. prescriptions for H. pylori infections, 80% contained clarithromycin, said Carol Rockett, PharmD, associate vice president of RedHill Biopharma in Raleigh, N.C.

Dr. Rockett presented the findings at the annual meeting of the American College of Gastroenterology.

“Multiple talks [at the meeting] have suggested that the use of clarithromycin in H. pylori is obsolete,” she told this news organization. “Clarithromycin is particularly ineffective in people with a genetic variant that causes rapid metabolism.”

According to the 2017 ACG clinical guideline for treating H. pylori, patients diagnosed with this infection should be asked about their previous antibiotic exposure prior to treatment.

Additionally, clinicians should prescribe clarithromycin triple therapy with a proton pump inhibitor (PPI) and amoxicillin or metronidazole as a first-line treatment only in “regions where H. pylori clarithromycin resistance is known to be less than 15%” and in patients with no previous history of macrolide exposure.

The guideline puts bismuth quadruple therapy, consisting of a PPI, bismuth, tetracycline, and a nitroimidazole, at the top of its list of six alternative first-line therapies. However, three of the six alternatives include clarithromycin.
 

ERADICATE Hp and ERADICATE Hp2

To understand how U.S. physicians are treating patients with H. pylori, Dr. Rockett’s colleagues analyzed data from two phase 3 clinical trials of RedHill’s RHB-105 (Talicia): ERADICATE Hp and ERADICATE Hp2.

RHB-105 is an all-in‐one combination of omeprazole (40 mg), amoxicillin (1,000 mg), and rifabutin (50 mg) that the Food and Drug Administration approved for treatment of H pylori in 2019.

The researchers followed 38 subjects from ERADICATE Hp who remained positive for H. pylori after the study’s completion. A total of 33 had received a placebo in that trial, while the other 5 had received RHB-105.

The researchers obtained data on 31 of these patients. The overall cure rate was 61.3%. Of the 31 patients, 27 received a regimen including clarithromycin. Their cure rate was 59.3%.

Turning to ERADICATE Hp2, the researchers obtained data on 94 patients whose H. pylori infections persisted after the trial. Of those, 67 had received an active comparator (amoxicillin 250 mg and omeprazole 10 mg) and 27 had received RHB-105.

The overall cure rate was 56.2%. For the 48 subjects who received therapies including clarithromycin, the cure rate was 60.4%. For the 22 subjects who received a bismuth-based quadruple regimen, the cure rate was 45.4%.

In another analysis, the researchers crunched 12 months of numbers from IQVIA PharMetrics Plus medical and prescription claim database of over 1 million prescriptions for H. pylori. They found that 80% of the prescriptions made by gastroenterologists were for regimens containing clarithromycin. That proportion increased to 84% for physician assistants and internists, 85% for nurse practitioners, 86% for family practitioners, and 89% for general practitioners.

Finally, the researchers also analyzed patients for CYP2C19 gene status. They tested 65 subjects who received RHB-105 in ERADICATE Hp and all 445 subjects in ERADICATE Hp2. They found that 58.5% in ERADICATE Hp and 48.6% in ERADICATE Hp2 were normal metabolizers.

In 20 normal metabolizers who received clarithromycin, the drug eradicated the infection in 16 (80%). Out of 11 rapid metabolizers, clarithromycin eradicated the bacterium in 2 (18.2%). The difference was statistically significant (P = .0017).

“With clarithromycin, you can see that the efficacy is reduced in those patients who are rapid metabolizers,” Dr. Rockett said. “We didn’t see that with rifabutin [one of the drugs in RHB-105].”

Jared Magee, DO, MPH, a gastroenterology fellow at the Walter Reed National Military Medical Center in Bethesda, Md., said in treating H. pylori infections, he checks the patients’ medical records to see what antibiotics they have received in the past and generally begins treatment with the bismuth quadruple therapy.

“There is education needed to get the data out there that clarithromycin-based therapies may not be the right choice for patients,” he said. “There is a subset who will do well with it, but I think where we’re at now, with the frequency of macrolide prescriptions for other conditions, that clarithromycin is going to be a difficult therapy for a lot of people.”

Clinicians who are not gastroenterologists may not be aware of the guideline promulgated by the ACG, he pointed out.

Dr. Rockett is an employee of RedHill Biopharma. Dr. Magee has disclosed no relevant financial relationships. The study was funded by RedHill Biopharma.

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

Clinicians are prescribing clarithromycin at high rates for Helicobacter pylori infections, despite increasing resistance to this antibiotic, researchers say.

In an analysis of 1 million U.S. prescriptions for H. pylori infections, 80% contained clarithromycin, said Carol Rockett, PharmD, associate vice president of RedHill Biopharma in Raleigh, N.C.

Dr. Rockett presented the findings at the annual meeting of the American College of Gastroenterology.

“Multiple talks [at the meeting] have suggested that the use of clarithromycin in H. pylori is obsolete,” she told this news organization. “Clarithromycin is particularly ineffective in people with a genetic variant that causes rapid metabolism.”

According to the 2017 ACG clinical guideline for treating H. pylori, patients diagnosed with this infection should be asked about their previous antibiotic exposure prior to treatment.

Additionally, clinicians should prescribe clarithromycin triple therapy with a proton pump inhibitor (PPI) and amoxicillin or metronidazole as a first-line treatment only in “regions where H. pylori clarithromycin resistance is known to be less than 15%” and in patients with no previous history of macrolide exposure.

The guideline puts bismuth quadruple therapy, consisting of a PPI, bismuth, tetracycline, and a nitroimidazole, at the top of its list of six alternative first-line therapies. However, three of the six alternatives include clarithromycin.
 

ERADICATE Hp and ERADICATE Hp2

To understand how U.S. physicians are treating patients with H. pylori, Dr. Rockett’s colleagues analyzed data from two phase 3 clinical trials of RedHill’s RHB-105 (Talicia): ERADICATE Hp and ERADICATE Hp2.

RHB-105 is an all-in‐one combination of omeprazole (40 mg), amoxicillin (1,000 mg), and rifabutin (50 mg) that the Food and Drug Administration approved for treatment of H pylori in 2019.

The researchers followed 38 subjects from ERADICATE Hp who remained positive for H. pylori after the study’s completion. A total of 33 had received a placebo in that trial, while the other 5 had received RHB-105.

The researchers obtained data on 31 of these patients. The overall cure rate was 61.3%. Of the 31 patients, 27 received a regimen including clarithromycin. Their cure rate was 59.3%.

Turning to ERADICATE Hp2, the researchers obtained data on 94 patients whose H. pylori infections persisted after the trial. Of those, 67 had received an active comparator (amoxicillin 250 mg and omeprazole 10 mg) and 27 had received RHB-105.

The overall cure rate was 56.2%. For the 48 subjects who received therapies including clarithromycin, the cure rate was 60.4%. For the 22 subjects who received a bismuth-based quadruple regimen, the cure rate was 45.4%.

In another analysis, the researchers crunched 12 months of numbers from IQVIA PharMetrics Plus medical and prescription claim database of over 1 million prescriptions for H. pylori. They found that 80% of the prescriptions made by gastroenterologists were for regimens containing clarithromycin. That proportion increased to 84% for physician assistants and internists, 85% for nurse practitioners, 86% for family practitioners, and 89% for general practitioners.

Finally, the researchers also analyzed patients for CYP2C19 gene status. They tested 65 subjects who received RHB-105 in ERADICATE Hp and all 445 subjects in ERADICATE Hp2. They found that 58.5% in ERADICATE Hp and 48.6% in ERADICATE Hp2 were normal metabolizers.

In 20 normal metabolizers who received clarithromycin, the drug eradicated the infection in 16 (80%). Out of 11 rapid metabolizers, clarithromycin eradicated the bacterium in 2 (18.2%). The difference was statistically significant (P = .0017).

“With clarithromycin, you can see that the efficacy is reduced in those patients who are rapid metabolizers,” Dr. Rockett said. “We didn’t see that with rifabutin [one of the drugs in RHB-105].”

Jared Magee, DO, MPH, a gastroenterology fellow at the Walter Reed National Military Medical Center in Bethesda, Md., said in treating H. pylori infections, he checks the patients’ medical records to see what antibiotics they have received in the past and generally begins treatment with the bismuth quadruple therapy.

“There is education needed to get the data out there that clarithromycin-based therapies may not be the right choice for patients,” he said. “There is a subset who will do well with it, but I think where we’re at now, with the frequency of macrolide prescriptions for other conditions, that clarithromycin is going to be a difficult therapy for a lot of people.”

Clinicians who are not gastroenterologists may not be aware of the guideline promulgated by the ACG, he pointed out.

Dr. Rockett is an employee of RedHill Biopharma. Dr. Magee has disclosed no relevant financial relationships. The study was funded by RedHill Biopharma.

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

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

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

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

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

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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