HIV

HIV continues to be a significant public health concern in the United States, with an estimated 1.2 million people currently living with the virus and more than 30,000 new diagnoses in 2020 alone.

Primary care clinicians can help decrease rates of HIV infection by prescribing pre-exposure prophylaxis to people who are sexually active.

But many do not.

“In medical school, we don’t spend much time discussing sexuality, sexual behavior, sexually transmitted infections, and such, so providers may feel uncomfortable asking what kind of sex their patient is having and with whom, whether they use a condom, and other basics,” said Matthew M. Hamill, MBChB, PhD, MPH, a specialist in sexually transmitted diseases at Johns Hopkins Medicine, Baltimore.

PrEP (pre-exposure prophylaxis) is an antiviral medication that cuts the risk of contracting HIV through sex by around 99% when taken as prescribed, according to the Centers for Disease Control and Prevention.

“Many people who would benefit from PrEP are not receiving this highly effective medication,” said John B. Wong, MD, a primary care internist and professor of medicine at Tufts University, Boston. The gap is particularly acute among Black, Hispanic, and Latino people, who are significantly more likely to be diagnosed with HIV but are much less likely than Whites to receive PrEP, he said.

Dr. Wong, a member of the U.S. Preventive Services Task Force, helped write the group’s new PrEP recommendations. Published in August, the guidelines call for clinicians to prescribe the drugs to adolescents and adults who do not have HIV but are at an increased risk for infection.

“Primary care physicians are ideally positioned to prescribe PrEP for their patients because they have longitudinal relationships: They get to know their patients, and hopefully their patients feel comfortable talking with them about their sexual health,” said Brandon Pollak, MD, a primary care physician and HIV specialist at the Ohio State University College of Medicine, Columbus.

Dr. Pollak, who was not involved with the USPSTF recommendations, cares for patients who are heterosexual and living with HIV.

Clinicians should consider PrEP for all patients who have sex with someone who has HIV, do not use condoms, or have had a sexually transmitted infection within the previous 6 months. Men who have sex with men, transgender women who have sex with men, people who inject illicit drugs or engage in transactional sex, and Black, Hispanic, and Latino individuals also are at increased risk for the infection.

“The vast majority of patients on PrEP in any form sail through with no problems; they have regular lab work and can follow up in person or by telemedicine,” Dr. Hamill said. “They tend to be young, fit people without complicated medical histories, and the medications are very well-tolerated, particularly if people expect some short-term side effects.”
 

What you need to know when prescribing PrEP

Prescribing PrEP is similar in complexity to prescribing hypertension or diabetes medications, Dr. Hamill said.

Because taking the medications while already infected with the virus can lead to the emergence of drug-resistant HIV, patients must have a negative HIV test before starting PrEP. In addition, the USPSTF recommends testing for other sexually transmitted infections and for pregnancy, if appropriate. The task force also recommends conducting kidney function and hepatitis B tests, and a lipid profile before starting specific types of PrEP.

HIV screening is also recommended at 3-month intervals.

“Providers may order labs done at 3- to 4-month intervals but only see patients in clinic once or twice per year, depending on patient needs and risk behaviors,” said Jill S. Blumenthal, MD, associate professor of medicine at UC San Diego Health.

Clinicians should consider medication adherence and whether a patient is likely to take a pill once a day or could benefit from receiving an injection every 2 months. Patients may experience side effects such as diarrhea or headache with oral PrEP or soreness at the injection site. In rare cases, some of the drugs may cause kidney toxicity or bone mineral loss, according to Dr. Hamill.

Three similarly effective forms of PrEP approved by the U.S. Food and Drug Administration enable clinicians to tailor the medications to the specific needs and preferences of each patient. Truvada (emtricitabine and tenofovir disoproxil fumarate) and Descovy (emtricitabine and tenofovir alafenamide) are both daily tablets, although the latter is not advised for people assigned female sex at birth who have receptive vaginal sex. Apretude (cabotegravir), an injectable agent, is not recommended for people who inject illegal drugs.

Patients with renal or bone disease are not good candidates for Truvada.

“Truvada can decrease bone density, so for someone with osteoporosis, you might choose Descovy or Apretude,” Dr. Pollak said. “For someone with chronic kidney disease, consider Descovy or Apretude. “If a patient has hepatitis B, Truvada or Descovy are appropriate, because hepatitis B is treatable.”

Patients taking an injectable PrEP may need more attention, because the concentration of the medication in the body decreases slowly and may linger for many months at low levels that don’t prevent HIV, according to Dr. Hamill. Someone who acquires HIV during that “tail” period might develop resistance to PrEP.

New research also showed that Descovy users were at elevated risk of developing hypertension and statin initiation, especially among those over age 40 years.

Primary care physicians may want to consult with renal specialists about medication safety in patients with severe kidney disease or with rheumatologists or endocrinologists about metabolic bone disease concerns, Dr. Hamill said.

Meanwhile, if a person begins a monogamous relationship and their risk for HIV drops, “it’s fine to stop taking PrEP tablets,” Dr. Pollak said. “I would still recommend routine HIV screening every 6 or 12 months or however often, depending on other risk factors.”

Caring for these patients entails ensuring labs are completed, monitoring adherence, ordering refills, and scheduling regular follow-up visits.

“For the vast majority of patients, the primary care physician is perfectly equipped for their care through the entire PrEP journey, from discussion and initiation to provision of PrEP,” and most cases do not require specialist care, Dr. Hamill said.

However, “if PrEP fails, which is exceedingly rare, primary care physicians should refer patients immediately, preferably with a warm handoff, for linkage to HIV care,” Dr. Blumenthal said.

Talking about PrEP opens the door to conversations with patients about sexual health and broader health issues, Dr. Hamill said. Although these may not come naturally to primary care clinicians, training is available. The National Network of STD Clinical Prevention Training Centers, funded by the CDC, trains providers on how to overcome their anxiety and have open, inclusive conversations about sexuality and sexual behaviors with transgender and gender-diverse, nonbinary people.

“People worry about saying the wrong thing, about causing offense,” Dr. Hamill said. “But once you get comfortable discussing sexuality, you may open conversations around other health issues.”
 

Barriers for patients

The task force identified several barriers to PrEP access for patients because of lack of trusting relationships with health care, the effects of structural racism on health disparities, and persistent biases within the health care system.

Racial and ethnic disparities in HIV incidence persist, with 42% of new diagnoses occurring among Black people, 27% among Hispanic or Latino people, and 26% among White people in 2020.

Rates of PrEP usage for a year or longer are also low. Sometimes the patient no longer needs PrEP, but barriers often involve the costs of taking time off from work and arranging transportation to clinic visits.

Although nearly all insurance plans and state Medicaid programs cover PrEP, if a patient does not have coverage, the drugs and required tests and office visits can be expensive.

“One of the biggest barriers for all providers is navigating our complicated health system and drug assistance programs,” said Mehri S. McKellar, MD, associate professor of medicine at Duke University School of Medicine, Durham, N.C.

But lower-cost FDA-approved generic emtricitabine/tenofovir disoproxil fumarate is now available, and clinicians can direct patients to programs that help provide the medications at low or no cost.

“Providing PrEP care is straightforward, beneficial, and satisfying,” Dr. Hamill said. “You help people protect themselves from a life-changing diagnosis, and the health system doesn’t need to pay the cost of treating HIV. Everyone wins.”

Dr. Hamill, Dr. McKellar, Dr. Pollak, and Dr. Wong have reported no relevant financial relationships. Dr. Blumenthal has reported a financial relationship with Gilead Sciences.

A version of this article appeared on Medscape.com.

HIV continues to be a significant public health concern in the United States, with an estimated 1.2 million people currently living with the virus and more than 30,000 new diagnoses in 2020 alone.

Primary care clinicians can help decrease rates of HIV infection by prescribing pre-exposure prophylaxis to people who are sexually active.

But many do not.

“In medical school, we don’t spend much time discussing sexuality, sexual behavior, sexually transmitted infections, and such, so providers may feel uncomfortable asking what kind of sex their patient is having and with whom, whether they use a condom, and other basics,” said Matthew M. Hamill, MBChB, PhD, MPH, a specialist in sexually transmitted diseases at Johns Hopkins Medicine, Baltimore.

PrEP (pre-exposure prophylaxis) is an antiviral medication that cuts the risk of contracting HIV through sex by around 99% when taken as prescribed, according to the Centers for Disease Control and Prevention.

“Many people who would benefit from PrEP are not receiving this highly effective medication,” said John B. Wong, MD, a primary care internist and professor of medicine at Tufts University, Boston. The gap is particularly acute among Black, Hispanic, and Latino people, who are significantly more likely to be diagnosed with HIV but are much less likely than Whites to receive PrEP, he said.

Dr. Wong, a member of the U.S. Preventive Services Task Force, helped write the group’s new PrEP recommendations. Published in August, the guidelines call for clinicians to prescribe the drugs to adolescents and adults who do not have HIV but are at an increased risk for infection.

“Primary care physicians are ideally positioned to prescribe PrEP for their patients because they have longitudinal relationships: They get to know their patients, and hopefully their patients feel comfortable talking with them about their sexual health,” said Brandon Pollak, MD, a primary care physician and HIV specialist at the Ohio State University College of Medicine, Columbus.

Dr. Pollak, who was not involved with the USPSTF recommendations, cares for patients who are heterosexual and living with HIV.

Clinicians should consider PrEP for all patients who have sex with someone who has HIV, do not use condoms, or have had a sexually transmitted infection within the previous 6 months. Men who have sex with men, transgender women who have sex with men, people who inject illicit drugs or engage in transactional sex, and Black, Hispanic, and Latino individuals also are at increased risk for the infection.

“The vast majority of patients on PrEP in any form sail through with no problems; they have regular lab work and can follow up in person or by telemedicine,” Dr. Hamill said. “They tend to be young, fit people without complicated medical histories, and the medications are very well-tolerated, particularly if people expect some short-term side effects.”
 

What you need to know when prescribing PrEP

Prescribing PrEP is similar in complexity to prescribing hypertension or diabetes medications, Dr. Hamill said.

Because taking the medications while already infected with the virus can lead to the emergence of drug-resistant HIV, patients must have a negative HIV test before starting PrEP. In addition, the USPSTF recommends testing for other sexually transmitted infections and for pregnancy, if appropriate. The task force also recommends conducting kidney function and hepatitis B tests, and a lipid profile before starting specific types of PrEP.

HIV screening is also recommended at 3-month intervals.

“Providers may order labs done at 3- to 4-month intervals but only see patients in clinic once or twice per year, depending on patient needs and risk behaviors,” said Jill S. Blumenthal, MD, associate professor of medicine at UC San Diego Health.

Clinicians should consider medication adherence and whether a patient is likely to take a pill once a day or could benefit from receiving an injection every 2 months. Patients may experience side effects such as diarrhea or headache with oral PrEP or soreness at the injection site. In rare cases, some of the drugs may cause kidney toxicity or bone mineral loss, according to Dr. Hamill.

Three similarly effective forms of PrEP approved by the U.S. Food and Drug Administration enable clinicians to tailor the medications to the specific needs and preferences of each patient. Truvada (emtricitabine and tenofovir disoproxil fumarate) and Descovy (emtricitabine and tenofovir alafenamide) are both daily tablets, although the latter is not advised for people assigned female sex at birth who have receptive vaginal sex. Apretude (cabotegravir), an injectable agent, is not recommended for people who inject illegal drugs.

Patients with renal or bone disease are not good candidates for Truvada.

“Truvada can decrease bone density, so for someone with osteoporosis, you might choose Descovy or Apretude,” Dr. Pollak said. “For someone with chronic kidney disease, consider Descovy or Apretude. “If a patient has hepatitis B, Truvada or Descovy are appropriate, because hepatitis B is treatable.”

Patients taking an injectable PrEP may need more attention, because the concentration of the medication in the body decreases slowly and may linger for many months at low levels that don’t prevent HIV, according to Dr. Hamill. Someone who acquires HIV during that “tail” period might develop resistance to PrEP.

New research also showed that Descovy users were at elevated risk of developing hypertension and statin initiation, especially among those over age 40 years.

Primary care physicians may want to consult with renal specialists about medication safety in patients with severe kidney disease or with rheumatologists or endocrinologists about metabolic bone disease concerns, Dr. Hamill said.

Meanwhile, if a person begins a monogamous relationship and their risk for HIV drops, “it’s fine to stop taking PrEP tablets,” Dr. Pollak said. “I would still recommend routine HIV screening every 6 or 12 months or however often, depending on other risk factors.”

Caring for these patients entails ensuring labs are completed, monitoring adherence, ordering refills, and scheduling regular follow-up visits.

“For the vast majority of patients, the primary care physician is perfectly equipped for their care through the entire PrEP journey, from discussion and initiation to provision of PrEP,” and most cases do not require specialist care, Dr. Hamill said.

However, “if PrEP fails, which is exceedingly rare, primary care physicians should refer patients immediately, preferably with a warm handoff, for linkage to HIV care,” Dr. Blumenthal said.

Talking about PrEP opens the door to conversations with patients about sexual health and broader health issues, Dr. Hamill said. Although these may not come naturally to primary care clinicians, training is available. The National Network of STD Clinical Prevention Training Centers, funded by the CDC, trains providers on how to overcome their anxiety and have open, inclusive conversations about sexuality and sexual behaviors with transgender and gender-diverse, nonbinary people.

“People worry about saying the wrong thing, about causing offense,” Dr. Hamill said. “But once you get comfortable discussing sexuality, you may open conversations around other health issues.”
 

Barriers for patients

The task force identified several barriers to PrEP access for patients because of lack of trusting relationships with health care, the effects of structural racism on health disparities, and persistent biases within the health care system.

Racial and ethnic disparities in HIV incidence persist, with 42% of new diagnoses occurring among Black people, 27% among Hispanic or Latino people, and 26% among White people in 2020.

Rates of PrEP usage for a year or longer are also low. Sometimes the patient no longer needs PrEP, but barriers often involve the costs of taking time off from work and arranging transportation to clinic visits.

Although nearly all insurance plans and state Medicaid programs cover PrEP, if a patient does not have coverage, the drugs and required tests and office visits can be expensive.

“One of the biggest barriers for all providers is navigating our complicated health system and drug assistance programs,” said Mehri S. McKellar, MD, associate professor of medicine at Duke University School of Medicine, Durham, N.C.

But lower-cost FDA-approved generic emtricitabine/tenofovir disoproxil fumarate is now available, and clinicians can direct patients to programs that help provide the medications at low or no cost.

“Providing PrEP care is straightforward, beneficial, and satisfying,” Dr. Hamill said. “You help people protect themselves from a life-changing diagnosis, and the health system doesn’t need to pay the cost of treating HIV. Everyone wins.”

Dr. Hamill, Dr. McKellar, Dr. Pollak, and Dr. Wong have reported no relevant financial relationships. Dr. Blumenthal has reported a financial relationship with Gilead Sciences.

A version of this article appeared on Medscape.com.

HIV continues to be a significant public health concern in the United States, with an estimated 1.2 million people currently living with the virus and more than 30,000 new diagnoses in 2020 alone.

Primary care clinicians can help decrease rates of HIV infection by prescribing pre-exposure prophylaxis to people who are sexually active.

But many do not.

“In medical school, we don’t spend much time discussing sexuality, sexual behavior, sexually transmitted infections, and such, so providers may feel uncomfortable asking what kind of sex their patient is having and with whom, whether they use a condom, and other basics,” said Matthew M. Hamill, MBChB, PhD, MPH, a specialist in sexually transmitted diseases at Johns Hopkins Medicine, Baltimore.

PrEP (pre-exposure prophylaxis) is an antiviral medication that cuts the risk of contracting HIV through sex by around 99% when taken as prescribed, according to the Centers for Disease Control and Prevention.

“Many people who would benefit from PrEP are not receiving this highly effective medication,” said John B. Wong, MD, a primary care internist and professor of medicine at Tufts University, Boston. The gap is particularly acute among Black, Hispanic, and Latino people, who are significantly more likely to be diagnosed with HIV but are much less likely than Whites to receive PrEP, he said.

Dr. Wong, a member of the U.S. Preventive Services Task Force, helped write the group’s new PrEP recommendations. Published in August, the guidelines call for clinicians to prescribe the drugs to adolescents and adults who do not have HIV but are at an increased risk for infection.

“Primary care physicians are ideally positioned to prescribe PrEP for their patients because they have longitudinal relationships: They get to know their patients, and hopefully their patients feel comfortable talking with them about their sexual health,” said Brandon Pollak, MD, a primary care physician and HIV specialist at the Ohio State University College of Medicine, Columbus.

Dr. Pollak, who was not involved with the USPSTF recommendations, cares for patients who are heterosexual and living with HIV.

Clinicians should consider PrEP for all patients who have sex with someone who has HIV, do not use condoms, or have had a sexually transmitted infection within the previous 6 months. Men who have sex with men, transgender women who have sex with men, people who inject illicit drugs or engage in transactional sex, and Black, Hispanic, and Latino individuals also are at increased risk for the infection.

“The vast majority of patients on PrEP in any form sail through with no problems; they have regular lab work and can follow up in person or by telemedicine,” Dr. Hamill said. “They tend to be young, fit people without complicated medical histories, and the medications are very well-tolerated, particularly if people expect some short-term side effects.”
 

What you need to know when prescribing PrEP

Prescribing PrEP is similar in complexity to prescribing hypertension or diabetes medications, Dr. Hamill said.

Because taking the medications while already infected with the virus can lead to the emergence of drug-resistant HIV, patients must have a negative HIV test before starting PrEP. In addition, the USPSTF recommends testing for other sexually transmitted infections and for pregnancy, if appropriate. The task force also recommends conducting kidney function and hepatitis B tests, and a lipid profile before starting specific types of PrEP.

HIV screening is also recommended at 3-month intervals.

“Providers may order labs done at 3- to 4-month intervals but only see patients in clinic once or twice per year, depending on patient needs and risk behaviors,” said Jill S. Blumenthal, MD, associate professor of medicine at UC San Diego Health.

Clinicians should consider medication adherence and whether a patient is likely to take a pill once a day or could benefit from receiving an injection every 2 months. Patients may experience side effects such as diarrhea or headache with oral PrEP or soreness at the injection site. In rare cases, some of the drugs may cause kidney toxicity or bone mineral loss, according to Dr. Hamill.

Three similarly effective forms of PrEP approved by the U.S. Food and Drug Administration enable clinicians to tailor the medications to the specific needs and preferences of each patient. Truvada (emtricitabine and tenofovir disoproxil fumarate) and Descovy (emtricitabine and tenofovir alafenamide) are both daily tablets, although the latter is not advised for people assigned female sex at birth who have receptive vaginal sex. Apretude (cabotegravir), an injectable agent, is not recommended for people who inject illegal drugs.

Patients with renal or bone disease are not good candidates for Truvada.

“Truvada can decrease bone density, so for someone with osteoporosis, you might choose Descovy or Apretude,” Dr. Pollak said. “For someone with chronic kidney disease, consider Descovy or Apretude. “If a patient has hepatitis B, Truvada or Descovy are appropriate, because hepatitis B is treatable.”

Patients taking an injectable PrEP may need more attention, because the concentration of the medication in the body decreases slowly and may linger for many months at low levels that don’t prevent HIV, according to Dr. Hamill. Someone who acquires HIV during that “tail” period might develop resistance to PrEP.

New research also showed that Descovy users were at elevated risk of developing hypertension and statin initiation, especially among those over age 40 years.

Primary care physicians may want to consult with renal specialists about medication safety in patients with severe kidney disease or with rheumatologists or endocrinologists about metabolic bone disease concerns, Dr. Hamill said.

Meanwhile, if a person begins a monogamous relationship and their risk for HIV drops, “it’s fine to stop taking PrEP tablets,” Dr. Pollak said. “I would still recommend routine HIV screening every 6 or 12 months or however often, depending on other risk factors.”

Caring for these patients entails ensuring labs are completed, monitoring adherence, ordering refills, and scheduling regular follow-up visits.

“For the vast majority of patients, the primary care physician is perfectly equipped for their care through the entire PrEP journey, from discussion and initiation to provision of PrEP,” and most cases do not require specialist care, Dr. Hamill said.

However, “if PrEP fails, which is exceedingly rare, primary care physicians should refer patients immediately, preferably with a warm handoff, for linkage to HIV care,” Dr. Blumenthal said.

Talking about PrEP opens the door to conversations with patients about sexual health and broader health issues, Dr. Hamill said. Although these may not come naturally to primary care clinicians, training is available. The National Network of STD Clinical Prevention Training Centers, funded by the CDC, trains providers on how to overcome their anxiety and have open, inclusive conversations about sexuality and sexual behaviors with transgender and gender-diverse, nonbinary people.

“People worry about saying the wrong thing, about causing offense,” Dr. Hamill said. “But once you get comfortable discussing sexuality, you may open conversations around other health issues.”
 

Barriers for patients

The task force identified several barriers to PrEP access for patients because of lack of trusting relationships with health care, the effects of structural racism on health disparities, and persistent biases within the health care system.

Racial and ethnic disparities in HIV incidence persist, with 42% of new diagnoses occurring among Black people, 27% among Hispanic or Latino people, and 26% among White people in 2020.

Rates of PrEP usage for a year or longer are also low. Sometimes the patient no longer needs PrEP, but barriers often involve the costs of taking time off from work and arranging transportation to clinic visits.

Although nearly all insurance plans and state Medicaid programs cover PrEP, if a patient does not have coverage, the drugs and required tests and office visits can be expensive.

“One of the biggest barriers for all providers is navigating our complicated health system and drug assistance programs,” said Mehri S. McKellar, MD, associate professor of medicine at Duke University School of Medicine, Durham, N.C.

But lower-cost FDA-approved generic emtricitabine/tenofovir disoproxil fumarate is now available, and clinicians can direct patients to programs that help provide the medications at low or no cost.

“Providing PrEP care is straightforward, beneficial, and satisfying,” Dr. Hamill said. “You help people protect themselves from a life-changing diagnosis, and the health system doesn’t need to pay the cost of treating HIV. Everyone wins.”

Dr. Hamill, Dr. McKellar, Dr. Pollak, and Dr. Wong have reported no relevant financial relationships. Dr. Blumenthal has reported a financial relationship with Gilead Sciences.

A version of this article appeared on Medscape.com.

The U.S. Preventive Services Task Force is expanding its recommendation for antiretrovirals in HIV now that more options are available on the market.

“With these new options we could potentially extend pre-exposure prophylaxis (PrEP) to a wider population,” says James Stevermer, MD, a member of the task force and a professor of family and community medicine at the University of Missouri–Columbia.

The guidance, published in JAMA, updates the group’s previous recommendation from 2019 to take into account the new options that have become available since the U.S. Food and Drug Administration approvals that included a long-acting injectable form.

In the original report, daily oral tenofovir disoproxil fumarate with emtricitabine was the only approved medication available and the task force recommended it. Since then, two new regimens have been approved: daily oral tenofovir alafenamide with emtricitabine and the long-acting injectable cabotegravir.

The task force is backing all three options and is recommending that clinicians use whichever formulation is most appropriate for their patients at risk for HIV infection.
 

Task force in primary and preventive care

The USPSTF is a volunteer group of experts in primary and preventive care who make recommendations on the best preventative interventions clinicians should take on everything from cancer screening, to preventive aspirin use, to behavioral counseling. The group is convened and supported by the Agency for Healthcare Research and Quality.

Recommendations from this group are particularly helpful for clinicians who may not see HIV as their area of expertise, says Carolyn Chu, MD, chief medical officer of the American Academy of HIV Medicine. “Hopefully, this will catch the eye of people who are not tracking all of the HIV updates,” she says.

A person’s risk for infection is mostly based on their behavior, Dr. Stevermer says. Those who use injectable drugs, particularly if they share needles, those who use condoms inconsistently and do not know their partner’s HIV status, and those who have recently had bacterial sexually transmitted infections like gonorrhea and syphilis are all at higher risk.

The efficacy of each of the three options is close enough to equal that it doesn’t usually matter which is prescribed, according to the task force. However, daily oral tenofovir alafenamide with emtricitabine is not approved for use by people engaging in receptive vaginal sex. For most people, the best medication option is the one they are most likely able to integrate into their routine. Cabotegravir, for example, which requires injections every 2 months, is an easier method for some people, particularly those who don’t think they could successfully take a daily pill.
 

Reducing risk

“The evidence is very clear that being able to adhere to taking the medication daily was very closely associated with the effectiveness of PrEP,” Dr. Stevermer says. “So, everything that we can do to make sure that the person who wants to prevent HIV is getting their PrEP as it is supposed to be taken makes it that much more effective.”

Expanding access to antiretrovirals among at-risk groups is an important part of the Ending the HIV Epidemic in the United States initiative that aims to reduce new HIV cases by 90% by 2030.

But an editorial published alongside the recommendation in JAMA notes that uptake of PrEP has been disproportionately low among populations most heavily affected by HIV.

In 2021, 78% of White people expected to benefit from PrEP received it, compared with just 11% of Black people and 21% of Hispanic people, despite both of those populations having a higher incidence of HIV than Whites. PrEP use is also substantially lower among cisgender and transgender women, youth, and people who inject drugs.

“We have an intervention that can markedly reduce people’s risk of getting HIV and so we want to make sure we get this out to all those populations at increased risk,” Dr. Stevermer says.

Having multiple options when it comes to PrEP is a big part of expanding access to the treatment for underserved groups, Dr. Chu says. “Even though oral tenofovir disoproxil fumarate with emtricitabine has been out for a while, we know it’s not getting to everyone, and there may be clinical circumstances that means it’s not the right option,” she says. “Making sure we are supporting choices so people can make the decision for themselves is important.”

But doctors also need to be willing to have an open conversation with their patients and bring up the topic of PrEP in a way that doesn’t feel judgmental or stigmatizing, Dr. Chu says.

It is also important not to make assumptions about who would want to talk about medication, she adds. “How can we change the narrative around PrEP?” she asks. “The evidence is there, these medications are effective and safe; weave PrEP into your preventive care portfolio to at least start the conversation.”

A version of this article appeared on Medscape.com.

The U.S. Preventive Services Task Force is expanding its recommendation for antiretrovirals in HIV now that more options are available on the market.

“With these new options we could potentially extend pre-exposure prophylaxis (PrEP) to a wider population,” says James Stevermer, MD, a member of the task force and a professor of family and community medicine at the University of Missouri–Columbia.

The guidance, published in JAMA, updates the group’s previous recommendation from 2019 to take into account the new options that have become available since the U.S. Food and Drug Administration approvals that included a long-acting injectable form.

In the original report, daily oral tenofovir disoproxil fumarate with emtricitabine was the only approved medication available and the task force recommended it. Since then, two new regimens have been approved: daily oral tenofovir alafenamide with emtricitabine and the long-acting injectable cabotegravir.

The task force is backing all three options and is recommending that clinicians use whichever formulation is most appropriate for their patients at risk for HIV infection.
 

Task force in primary and preventive care

The USPSTF is a volunteer group of experts in primary and preventive care who make recommendations on the best preventative interventions clinicians should take on everything from cancer screening, to preventive aspirin use, to behavioral counseling. The group is convened and supported by the Agency for Healthcare Research and Quality.

Recommendations from this group are particularly helpful for clinicians who may not see HIV as their area of expertise, says Carolyn Chu, MD, chief medical officer of the American Academy of HIV Medicine. “Hopefully, this will catch the eye of people who are not tracking all of the HIV updates,” she says.

A person’s risk for infection is mostly based on their behavior, Dr. Stevermer says. Those who use injectable drugs, particularly if they share needles, those who use condoms inconsistently and do not know their partner’s HIV status, and those who have recently had bacterial sexually transmitted infections like gonorrhea and syphilis are all at higher risk.

The efficacy of each of the three options is close enough to equal that it doesn’t usually matter which is prescribed, according to the task force. However, daily oral tenofovir alafenamide with emtricitabine is not approved for use by people engaging in receptive vaginal sex. For most people, the best medication option is the one they are most likely able to integrate into their routine. Cabotegravir, for example, which requires injections every 2 months, is an easier method for some people, particularly those who don’t think they could successfully take a daily pill.
 

Reducing risk

“The evidence is very clear that being able to adhere to taking the medication daily was very closely associated with the effectiveness of PrEP,” Dr. Stevermer says. “So, everything that we can do to make sure that the person who wants to prevent HIV is getting their PrEP as it is supposed to be taken makes it that much more effective.”

Expanding access to antiretrovirals among at-risk groups is an important part of the Ending the HIV Epidemic in the United States initiative that aims to reduce new HIV cases by 90% by 2030.

But an editorial published alongside the recommendation in JAMA notes that uptake of PrEP has been disproportionately low among populations most heavily affected by HIV.

In 2021, 78% of White people expected to benefit from PrEP received it, compared with just 11% of Black people and 21% of Hispanic people, despite both of those populations having a higher incidence of HIV than Whites. PrEP use is also substantially lower among cisgender and transgender women, youth, and people who inject drugs.

“We have an intervention that can markedly reduce people’s risk of getting HIV and so we want to make sure we get this out to all those populations at increased risk,” Dr. Stevermer says.

Having multiple options when it comes to PrEP is a big part of expanding access to the treatment for underserved groups, Dr. Chu says. “Even though oral tenofovir disoproxil fumarate with emtricitabine has been out for a while, we know it’s not getting to everyone, and there may be clinical circumstances that means it’s not the right option,” she says. “Making sure we are supporting choices so people can make the decision for themselves is important.”

But doctors also need to be willing to have an open conversation with their patients and bring up the topic of PrEP in a way that doesn’t feel judgmental or stigmatizing, Dr. Chu says.

It is also important not to make assumptions about who would want to talk about medication, she adds. “How can we change the narrative around PrEP?” she asks. “The evidence is there, these medications are effective and safe; weave PrEP into your preventive care portfolio to at least start the conversation.”

A version of this article appeared on Medscape.com.

The U.S. Preventive Services Task Force is expanding its recommendation for antiretrovirals in HIV now that more options are available on the market.

“With these new options we could potentially extend pre-exposure prophylaxis (PrEP) to a wider population,” says James Stevermer, MD, a member of the task force and a professor of family and community medicine at the University of Missouri–Columbia.

The guidance, published in JAMA, updates the group’s previous recommendation from 2019 to take into account the new options that have become available since the U.S. Food and Drug Administration approvals that included a long-acting injectable form.

In the original report, daily oral tenofovir disoproxil fumarate with emtricitabine was the only approved medication available and the task force recommended it. Since then, two new regimens have been approved: daily oral tenofovir alafenamide with emtricitabine and the long-acting injectable cabotegravir.

The task force is backing all three options and is recommending that clinicians use whichever formulation is most appropriate for their patients at risk for HIV infection.
 

Task force in primary and preventive care

The USPSTF is a volunteer group of experts in primary and preventive care who make recommendations on the best preventative interventions clinicians should take on everything from cancer screening, to preventive aspirin use, to behavioral counseling. The group is convened and supported by the Agency for Healthcare Research and Quality.

Recommendations from this group are particularly helpful for clinicians who may not see HIV as their area of expertise, says Carolyn Chu, MD, chief medical officer of the American Academy of HIV Medicine. “Hopefully, this will catch the eye of people who are not tracking all of the HIV updates,” she says.

A person’s risk for infection is mostly based on their behavior, Dr. Stevermer says. Those who use injectable drugs, particularly if they share needles, those who use condoms inconsistently and do not know their partner’s HIV status, and those who have recently had bacterial sexually transmitted infections like gonorrhea and syphilis are all at higher risk.

The efficacy of each of the three options is close enough to equal that it doesn’t usually matter which is prescribed, according to the task force. However, daily oral tenofovir alafenamide with emtricitabine is not approved for use by people engaging in receptive vaginal sex. For most people, the best medication option is the one they are most likely able to integrate into their routine. Cabotegravir, for example, which requires injections every 2 months, is an easier method for some people, particularly those who don’t think they could successfully take a daily pill.
 

Reducing risk

“The evidence is very clear that being able to adhere to taking the medication daily was very closely associated with the effectiveness of PrEP,” Dr. Stevermer says. “So, everything that we can do to make sure that the person who wants to prevent HIV is getting their PrEP as it is supposed to be taken makes it that much more effective.”

Expanding access to antiretrovirals among at-risk groups is an important part of the Ending the HIV Epidemic in the United States initiative that aims to reduce new HIV cases by 90% by 2030.

But an editorial published alongside the recommendation in JAMA notes that uptake of PrEP has been disproportionately low among populations most heavily affected by HIV.

In 2021, 78% of White people expected to benefit from PrEP received it, compared with just 11% of Black people and 21% of Hispanic people, despite both of those populations having a higher incidence of HIV than Whites. PrEP use is also substantially lower among cisgender and transgender women, youth, and people who inject drugs.

“We have an intervention that can markedly reduce people’s risk of getting HIV and so we want to make sure we get this out to all those populations at increased risk,” Dr. Stevermer says.

Having multiple options when it comes to PrEP is a big part of expanding access to the treatment for underserved groups, Dr. Chu says. “Even though oral tenofovir disoproxil fumarate with emtricitabine has been out for a while, we know it’s not getting to everyone, and there may be clinical circumstances that means it’s not the right option,” she says. “Making sure we are supporting choices so people can make the decision for themselves is important.”

But doctors also need to be willing to have an open conversation with their patients and bring up the topic of PrEP in a way that doesn’t feel judgmental or stigmatizing, Dr. Chu says.

It is also important not to make assumptions about who would want to talk about medication, she adds. “How can we change the narrative around PrEP?” she asks. “The evidence is there, these medications are effective and safe; weave PrEP into your preventive care portfolio to at least start the conversation.”

A version of this article appeared on Medscape.com.

Aggressive marketing of OxyContin in the mid-1990s not only fueled the opioid crisis but also the spread of infectious diseases associated with injection drug use, a new analysis shows.

The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.

“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.

Their study was published online in Health Affairs.
 

Long-term effects revealed

Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.

Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.

Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.

Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.

Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.

High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.

“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.

Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.

“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.

Purdue Pharma did not provide a comment on the study.

Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.

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

Aggressive marketing of OxyContin in the mid-1990s not only fueled the opioid crisis but also the spread of infectious diseases associated with injection drug use, a new analysis shows.

The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.

“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.

Their study was published online in Health Affairs.
 

Long-term effects revealed

Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.

Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.

Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.

Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.

Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.

High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.

“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.

Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.

“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.

Purdue Pharma did not provide a comment on the study.

Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.

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

Aggressive marketing of OxyContin in the mid-1990s not only fueled the opioid crisis but also the spread of infectious diseases associated with injection drug use, a new analysis shows.

The uptick in rates of infectious diseases, namely, hepatitis and infective endocarditis, occurred after 2010, when OxyContin maker Purdue Pharma reformulated OxyContin to make it harder to crush and snort. This led many people who were already addicted to the powerful pain pills to move on to injecting heroin or fentanyl, which fueled the spread of infectious disease.

“Our results suggest that the mortality and morbidity consequences of OxyContin marketing continue to be salient more than 25 years later,” write Julia Dennett, PhD, and Gregg Gonsalves, PhD, with Yale University School of Public Health, New Haven, Conn.

Their study was published online in Health Affairs.
 

Long-term effects revealed

Until now, the long-term effects of widespread OxyContin marketing with regard to complications of injection drug use were unknown.

Dr. Dennett and Dr. Gonsalves evaluated the effects of OxyContin marketing on the long-term trajectories of various injection drug use–related outcomes. Using a difference-in-difference analysis, they compared states with high vs. low exposure to OxyContin marketing before and after the 2010 reformulation of the drug.

Before 2010, rates of infections associated with injection drug use and overdose deaths were similar in high- and low-marketing states, they found.

Those rates diverged after the 2010 reformulation, with more infections related to injection drug use in states exposed to more marketing.

Specifically, from 2010 until 2020, high-exposure states saw, on average, an additional 0.85 acute hepatitis B cases, 0.83 hepatitis C cases, and 0.62 cases of death from infective endocarditis per 100,000 residents.

High-exposure states also had 5.3 more deaths per 100,000 residents from synthetic opioid overdose.

“Prior to 2010, among these states, there were generally no statistically significant differences in these outcomes. After 2010, you saw them diverge dramatically,” Dr. Dennett said in a news release.

Dr. Dennett and Dr. Gonsalves say their findings support the view that the opioid epidemic is creating a converging public health crisis, as it is fueling a surge in infectious diseases, particularly hepatitis, infective endocarditis, and HIV.

“This study highlights a critical need for actions to address the spread of viral and bacterial infections and overdose associated with injection drug use, both in the states that were subject to Purdue’s promotional campaign and across the U.S. more broadly,” they add.

Purdue Pharma did not provide a comment on the study.

Funding for the study was provided by the National Institute on Drug Abuse. Disclosures for Dr. Dennett and Dr. Gonsalves were not available.

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

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

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

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

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

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

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

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

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

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

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

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

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

Clinics have been coming up with new ways to add injections to their offerings ever since a new long-acting formulation of cabotegravir has been available to treat people with HIV.

At the Whitman-Walker Health Center, Washington, community health workers see about 3,200 antiretroviral users a year. With long-acting injections now available, the clinic opted to integrate the new medications into its peer staff program.

“Our peer workers are very competent,” said Rupa Patel, MD, MPH, medical liason of the pre-exposure prophylaxis for HIV prevention program at Washington University at St. Louis.* “They do phlebotomy, they give you your meds. They’re your main doctor until you really need to see the doctor.”

In the peer staff program, workers are trained in a 4-month medical residency–style program that shows them how to test for HIV, inject long-acting formulations of new drugs, and conduct follow-up visits.

Presenting the new approach at the International AIDS Society Conference on HIV Science, Dr. Patel reported that 139 people have received long-acting injections at the clinic since the program launched with a total of 314 injections administered.

The training program includes lectures, mock injection, and client care sessions, observation and supervised administration, a written exam, and case review sessions.

Retention for the second injection was 95%, with 91% of injections given within the 14-day window. For the third injection, retention was 91%, with 63% given within the window.

The program reports a high level of client satisfaction with the peer-administered injections, which are also given in a room decorated with a beach theme and music to help calm people who might be nervous of receiving shots.

“Our retention is going to be the highest compared to other clinics because your peer, your friend, is reminding you and comforting you and telling you: ‘Don’t worry, I’m on the injection too,’ ” Dr. Patel said.

Andrew Grulich, MD, PhD, head of the HIV epidemiology and prevention program at the Kirby Institute, Sydney, pointed out there is tension between wanting to use long-acting injectables for people who are struggling with taking oral therapies daily and the need to ensure that they come back for their injections on time.

“I think it’s a potential way forward – we’re learning as we’re going with these new forms of therapy,” he said in an interview. “It is absolutely critical that people turn up on time for those injections, and if they don’t, resistance can be an issue.”

Presenting new data from another project at the HIV Clinic at San Francisco General Hospital, Monica Gandhi, MD, MPH, told the conference: “There are multiple reasons why it’s hard to take oral antiretrovirals every day.”

At the HIV Clinic in San Francisco General, people without homes, those with mental illness, and those using stimulants receive care.

The clinical trials for long-acting injectable antiretrovirals included only people who were virologically suppressed, which is also the Food and Drug Administration criteria for use. However, this clinic offered long-acting injections to patients with viremia because it was too difficult for them to take a daily pill.

In a comment, Dr. Gandhi, director of the University of California, San Francisco’s Center for AIDS Research, said: “We don’t call people hard to reach, we call them hardly reached because it’s not their fault.” There are just all of these issues that have made it harder for them to take medication consistently.

Dr. Gandhi reported that, of the 133 people being treated with long-acting injectable cabotegravir and rilpivirine at the clinic through this program, 57 had viremia at baseline.

However, only two of these patients experienced virologic failure while on the injectable antiretroviral program. The overall virologic failure rate was 1.5%, which was equivalent to that seen in clinical trials in virologically suppressed individuals.

The results presented at the conference and were also published in Annals of Internal Medicine.

The clinic found that 73% of people attended their injection appointments on time, and those who did not were followed up with telephone calls to ensure they received their injection within the 14-day window.

Dr. Gandhi said people were highly motivated to turn up for their injection appointments. “They are virologically suppressed, so it feels so amazing. They’re self-motivated for the first time to want to get an injection.”

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

*Correction, 8/4/23: An earlier version of this article misstated Dr. Patel's university affiliation.

Clinics have been coming up with new ways to add injections to their offerings ever since a new long-acting formulation of cabotegravir has been available to treat people with HIV.

At the Whitman-Walker Health Center, Washington, community health workers see about 3,200 antiretroviral users a year. With long-acting injections now available, the clinic opted to integrate the new medications into its peer staff program.

“Our peer workers are very competent,” said Rupa Patel, MD, MPH, medical liason of the pre-exposure prophylaxis for HIV prevention program at Washington University at St. Louis.* “They do phlebotomy, they give you your meds. They’re your main doctor until you really need to see the doctor.”

In the peer staff program, workers are trained in a 4-month medical residency–style program that shows them how to test for HIV, inject long-acting formulations of new drugs, and conduct follow-up visits.

Presenting the new approach at the International AIDS Society Conference on HIV Science, Dr. Patel reported that 139 people have received long-acting injections at the clinic since the program launched with a total of 314 injections administered.

The training program includes lectures, mock injection, and client care sessions, observation and supervised administration, a written exam, and case review sessions.

Retention for the second injection was 95%, with 91% of injections given within the 14-day window. For the third injection, retention was 91%, with 63% given within the window.

The program reports a high level of client satisfaction with the peer-administered injections, which are also given in a room decorated with a beach theme and music to help calm people who might be nervous of receiving shots.

“Our retention is going to be the highest compared to other clinics because your peer, your friend, is reminding you and comforting you and telling you: ‘Don’t worry, I’m on the injection too,’ ” Dr. Patel said.

Andrew Grulich, MD, PhD, head of the HIV epidemiology and prevention program at the Kirby Institute, Sydney, pointed out there is tension between wanting to use long-acting injectables for people who are struggling with taking oral therapies daily and the need to ensure that they come back for their injections on time.

“I think it’s a potential way forward – we’re learning as we’re going with these new forms of therapy,” he said in an interview. “It is absolutely critical that people turn up on time for those injections, and if they don’t, resistance can be an issue.”

Presenting new data from another project at the HIV Clinic at San Francisco General Hospital, Monica Gandhi, MD, MPH, told the conference: “There are multiple reasons why it’s hard to take oral antiretrovirals every day.”

At the HIV Clinic in San Francisco General, people without homes, those with mental illness, and those using stimulants receive care.

The clinical trials for long-acting injectable antiretrovirals included only people who were virologically suppressed, which is also the Food and Drug Administration criteria for use. However, this clinic offered long-acting injections to patients with viremia because it was too difficult for them to take a daily pill.

In a comment, Dr. Gandhi, director of the University of California, San Francisco’s Center for AIDS Research, said: “We don’t call people hard to reach, we call them hardly reached because it’s not their fault.” There are just all of these issues that have made it harder for them to take medication consistently.

Dr. Gandhi reported that, of the 133 people being treated with long-acting injectable cabotegravir and rilpivirine at the clinic through this program, 57 had viremia at baseline.

However, only two of these patients experienced virologic failure while on the injectable antiretroviral program. The overall virologic failure rate was 1.5%, which was equivalent to that seen in clinical trials in virologically suppressed individuals.

The results presented at the conference and were also published in Annals of Internal Medicine.

The clinic found that 73% of people attended their injection appointments on time, and those who did not were followed up with telephone calls to ensure they received their injection within the 14-day window.

Dr. Gandhi said people were highly motivated to turn up for their injection appointments. “They are virologically suppressed, so it feels so amazing. They’re self-motivated for the first time to want to get an injection.”

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

*Correction, 8/4/23: An earlier version of this article misstated Dr. Patel's university affiliation.

Clinics have been coming up with new ways to add injections to their offerings ever since a new long-acting formulation of cabotegravir has been available to treat people with HIV.

At the Whitman-Walker Health Center, Washington, community health workers see about 3,200 antiretroviral users a year. With long-acting injections now available, the clinic opted to integrate the new medications into its peer staff program.

“Our peer workers are very competent,” said Rupa Patel, MD, MPH, medical liason of the pre-exposure prophylaxis for HIV prevention program at Washington University at St. Louis.* “They do phlebotomy, they give you your meds. They’re your main doctor until you really need to see the doctor.”

In the peer staff program, workers are trained in a 4-month medical residency–style program that shows them how to test for HIV, inject long-acting formulations of new drugs, and conduct follow-up visits.

Presenting the new approach at the International AIDS Society Conference on HIV Science, Dr. Patel reported that 139 people have received long-acting injections at the clinic since the program launched with a total of 314 injections administered.

The training program includes lectures, mock injection, and client care sessions, observation and supervised administration, a written exam, and case review sessions.

Retention for the second injection was 95%, with 91% of injections given within the 14-day window. For the third injection, retention was 91%, with 63% given within the window.

The program reports a high level of client satisfaction with the peer-administered injections, which are also given in a room decorated with a beach theme and music to help calm people who might be nervous of receiving shots.

“Our retention is going to be the highest compared to other clinics because your peer, your friend, is reminding you and comforting you and telling you: ‘Don’t worry, I’m on the injection too,’ ” Dr. Patel said.

Andrew Grulich, MD, PhD, head of the HIV epidemiology and prevention program at the Kirby Institute, Sydney, pointed out there is tension between wanting to use long-acting injectables for people who are struggling with taking oral therapies daily and the need to ensure that they come back for their injections on time.

“I think it’s a potential way forward – we’re learning as we’re going with these new forms of therapy,” he said in an interview. “It is absolutely critical that people turn up on time for those injections, and if they don’t, resistance can be an issue.”

Presenting new data from another project at the HIV Clinic at San Francisco General Hospital, Monica Gandhi, MD, MPH, told the conference: “There are multiple reasons why it’s hard to take oral antiretrovirals every day.”

At the HIV Clinic in San Francisco General, people without homes, those with mental illness, and those using stimulants receive care.

The clinical trials for long-acting injectable antiretrovirals included only people who were virologically suppressed, which is also the Food and Drug Administration criteria for use. However, this clinic offered long-acting injections to patients with viremia because it was too difficult for them to take a daily pill.

In a comment, Dr. Gandhi, director of the University of California, San Francisco’s Center for AIDS Research, said: “We don’t call people hard to reach, we call them hardly reached because it’s not their fault.” There are just all of these issues that have made it harder for them to take medication consistently.

Dr. Gandhi reported that, of the 133 people being treated with long-acting injectable cabotegravir and rilpivirine at the clinic through this program, 57 had viremia at baseline.

However, only two of these patients experienced virologic failure while on the injectable antiretroviral program. The overall virologic failure rate was 1.5%, which was equivalent to that seen in clinical trials in virologically suppressed individuals.

The results presented at the conference and were also published in Annals of Internal Medicine.

The clinic found that 73% of people attended their injection appointments on time, and those who did not were followed up with telephone calls to ensure they received their injection within the 14-day window.

Dr. Gandhi said people were highly motivated to turn up for their injection appointments. “They are virologically suppressed, so it feels so amazing. They’re self-motivated for the first time to want to get an injection.”

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

*Correction, 8/4/23: An earlier version of this article misstated Dr. Patel's university affiliation.

BRISBANE, AUSTRALIA – The year was 1987 and the Grim Reaper (a personification of death), holding a large scythe, rolled a 10-pin bowling ball through a dark, foggy place. In the advertisement on television, the cloaked skeleton aimed the bowling ball at the other end of a lane where a group of people stood in place of pins.

Who would fall next?

In the 1980s, cases of HIV were rising in the community and people in Australia and elsewhere were dying of AIDS. The Australian government opted to use mainstream media to deliver a blunt message through advertising to raise awareness about the health risk and how to manage HIV in the community.

But the campaign also contributed to stigma for those living with the disease and especially those in the gay community who felt ostracized by rising public concern.

In the inner city of Sydney, a few thousand people died of AIDS, Andrew Grulich, MD, PhD, from the Kirby Institute at the University of New South Wales, Sydney, and involved in tracking cases, said in an interview. “Sydney was devastated by AIDS, it was truly devastated.”

HIV and AIDS quickly became an even more severe problem for several countries around Australia in Thailand, Papua New Guinea, and beyond. After HIV was first reported in Thailand in 1984, the region had the highest prevalence of HIV in Southeast Asia. Through the 1990s in Papua New Guinea, HIV prevalence rose steeply as well.

By 2010, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set a target of a 90% reduction in HIV incidence, a 90% reduction in AIDS deaths by 2030, and 95% of people living with HIV and AIDS being aware of their status, on treatment, and having an undetectable viral load.

Since then, significant progress has been made globally with 86% of people knowing their HIV status. However, new infections persist at a rate that has not dropped as fast as possible.
 

New infections

According to the latest UNAIDS report, regions of North America and western and central Europe showed a 23% decline in new infections from 2010 to 2022, below the target 90% reduction.

Some regions of the United States have seen significant declines in new HIV infections. San Francisco has a 67% drop in new diagnoses. And now, along with the District of Columbia, the four states with the highest HIV rates are New York, Maryland, Georgia, and Florida.

Several countries in eastern and southern Africa are close to achieving their target HIV reduction of 90%.

Mitchell Warren, executive director of AVAC for global health advocacy, access, and equity, said that many of the low- and middle-income countries that are on track to achieve targets are able to do so because of support from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis, and Malaria.

“That foreign development assistance is transforming the AIDS response in a number of African countries, and yet at home, in various states and municipalities, not only are we not reaching that effort, we don’t even use those targets,” Mr. Warren pointed out.

“We might see municipalities that are performing well, but at a national level it’s frankly a disgrace by comparison, because we know what’s possible,” Mr. Warren said.
 

Lowering cases

Today, in the inner city of Sydney, new HIV diagnoses have plummeted by 88%, which puts the area on track to achieve the 90% UNAIDS target ahead of schedule.

Dr. Grulich and his team at the Kirby Institute are tracking new diagnoses by postal code and reported their encouraging findings here this week at the International AIDS Society Conference on HIV Science.

“This 88% decline is happening in an area where, in the ’80s and ’90s, a few thousand people died of AIDS,” Dr. Grulich told this news organization. “It feels close to miraculous.”

Dr. Grulich attributes some of the success to long-term government leadership that for the most part has been apolitical. HIV has been perceived by the public as an important health issue to be addressed. “We’ve never had a political contest over it,” he added. “We have politicians who are committed to evidence-based policy.”

In inner city Sydney, HIV prevention campaigns are a visible part of community life, Dr. Grulich explained. At public events, it is discussed; at bus stops, posters are on display; and passing trains have messages plastered to the side of them.

That community effort has consistently received government funding for years – albeit linked to key performance indicators – but it has enabled a high level of communication among government, community, clinicians, and researchers.

Another advantage is Australia’s universal health coverage, said Sharon Lewin, PhD, president of the International AIDS Society and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne. “One very clear difference for Australia is a health system that provides free medication and free prevention,” she said. “You can’t underestimate the impact that has on public health.”

Globally, significant progress has been made toward the UN’s 95-95-95 targets, with 86% of people with HIV now knowing their status, 88% of those being on treatment, and 93% of those having an undetectable viral load, “for a total of 75% of all people living with HIV worldwide with undetectable viral load,” Dr. Grulich pointed out.

But Dr. Lewin cautioned that now is not the time to take our eye off the ball, especially with respect to the 39 million or so people living with HIV globally, all of whom need lifelong treatment and care to manage their disease. “We also need to be aware that if we relax the investment, and people stop their treatment, transmission occurs again,” Dr. Lewin warned. “Despite the great news of potentially getting close to eliminating HIV transmission in Australia, HIV is far from over.”

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

BRISBANE, AUSTRALIA – The year was 1987 and the Grim Reaper (a personification of death), holding a large scythe, rolled a 10-pin bowling ball through a dark, foggy place. In the advertisement on television, the cloaked skeleton aimed the bowling ball at the other end of a lane where a group of people stood in place of pins.

Who would fall next?

In the 1980s, cases of HIV were rising in the community and people in Australia and elsewhere were dying of AIDS. The Australian government opted to use mainstream media to deliver a blunt message through advertising to raise awareness about the health risk and how to manage HIV in the community.

But the campaign also contributed to stigma for those living with the disease and especially those in the gay community who felt ostracized by rising public concern.

In the inner city of Sydney, a few thousand people died of AIDS, Andrew Grulich, MD, PhD, from the Kirby Institute at the University of New South Wales, Sydney, and involved in tracking cases, said in an interview. “Sydney was devastated by AIDS, it was truly devastated.”

HIV and AIDS quickly became an even more severe problem for several countries around Australia in Thailand, Papua New Guinea, and beyond. After HIV was first reported in Thailand in 1984, the region had the highest prevalence of HIV in Southeast Asia. Through the 1990s in Papua New Guinea, HIV prevalence rose steeply as well.

By 2010, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set a target of a 90% reduction in HIV incidence, a 90% reduction in AIDS deaths by 2030, and 95% of people living with HIV and AIDS being aware of their status, on treatment, and having an undetectable viral load.

Since then, significant progress has been made globally with 86% of people knowing their HIV status. However, new infections persist at a rate that has not dropped as fast as possible.
 

New infections

According to the latest UNAIDS report, regions of North America and western and central Europe showed a 23% decline in new infections from 2010 to 2022, below the target 90% reduction.

Some regions of the United States have seen significant declines in new HIV infections. San Francisco has a 67% drop in new diagnoses. And now, along with the District of Columbia, the four states with the highest HIV rates are New York, Maryland, Georgia, and Florida.

Several countries in eastern and southern Africa are close to achieving their target HIV reduction of 90%.

Mitchell Warren, executive director of AVAC for global health advocacy, access, and equity, said that many of the low- and middle-income countries that are on track to achieve targets are able to do so because of support from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis, and Malaria.

“That foreign development assistance is transforming the AIDS response in a number of African countries, and yet at home, in various states and municipalities, not only are we not reaching that effort, we don’t even use those targets,” Mr. Warren pointed out.

“We might see municipalities that are performing well, but at a national level it’s frankly a disgrace by comparison, because we know what’s possible,” Mr. Warren said.
 

Lowering cases

Today, in the inner city of Sydney, new HIV diagnoses have plummeted by 88%, which puts the area on track to achieve the 90% UNAIDS target ahead of schedule.

Dr. Grulich and his team at the Kirby Institute are tracking new diagnoses by postal code and reported their encouraging findings here this week at the International AIDS Society Conference on HIV Science.

“This 88% decline is happening in an area where, in the ’80s and ’90s, a few thousand people died of AIDS,” Dr. Grulich told this news organization. “It feels close to miraculous.”

Dr. Grulich attributes some of the success to long-term government leadership that for the most part has been apolitical. HIV has been perceived by the public as an important health issue to be addressed. “We’ve never had a political contest over it,” he added. “We have politicians who are committed to evidence-based policy.”

In inner city Sydney, HIV prevention campaigns are a visible part of community life, Dr. Grulich explained. At public events, it is discussed; at bus stops, posters are on display; and passing trains have messages plastered to the side of them.

That community effort has consistently received government funding for years – albeit linked to key performance indicators – but it has enabled a high level of communication among government, community, clinicians, and researchers.

Another advantage is Australia’s universal health coverage, said Sharon Lewin, PhD, president of the International AIDS Society and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne. “One very clear difference for Australia is a health system that provides free medication and free prevention,” she said. “You can’t underestimate the impact that has on public health.”

Globally, significant progress has been made toward the UN’s 95-95-95 targets, with 86% of people with HIV now knowing their status, 88% of those being on treatment, and 93% of those having an undetectable viral load, “for a total of 75% of all people living with HIV worldwide with undetectable viral load,” Dr. Grulich pointed out.

But Dr. Lewin cautioned that now is not the time to take our eye off the ball, especially with respect to the 39 million or so people living with HIV globally, all of whom need lifelong treatment and care to manage their disease. “We also need to be aware that if we relax the investment, and people stop their treatment, transmission occurs again,” Dr. Lewin warned. “Despite the great news of potentially getting close to eliminating HIV transmission in Australia, HIV is far from over.”

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

BRISBANE, AUSTRALIA – The year was 1987 and the Grim Reaper (a personification of death), holding a large scythe, rolled a 10-pin bowling ball through a dark, foggy place. In the advertisement on television, the cloaked skeleton aimed the bowling ball at the other end of a lane where a group of people stood in place of pins.

Who would fall next?

In the 1980s, cases of HIV were rising in the community and people in Australia and elsewhere were dying of AIDS. The Australian government opted to use mainstream media to deliver a blunt message through advertising to raise awareness about the health risk and how to manage HIV in the community.

But the campaign also contributed to stigma for those living with the disease and especially those in the gay community who felt ostracized by rising public concern.

In the inner city of Sydney, a few thousand people died of AIDS, Andrew Grulich, MD, PhD, from the Kirby Institute at the University of New South Wales, Sydney, and involved in tracking cases, said in an interview. “Sydney was devastated by AIDS, it was truly devastated.”

HIV and AIDS quickly became an even more severe problem for several countries around Australia in Thailand, Papua New Guinea, and beyond. After HIV was first reported in Thailand in 1984, the region had the highest prevalence of HIV in Southeast Asia. Through the 1990s in Papua New Guinea, HIV prevalence rose steeply as well.

By 2010, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set a target of a 90% reduction in HIV incidence, a 90% reduction in AIDS deaths by 2030, and 95% of people living with HIV and AIDS being aware of their status, on treatment, and having an undetectable viral load.

Since then, significant progress has been made globally with 86% of people knowing their HIV status. However, new infections persist at a rate that has not dropped as fast as possible.
 

New infections

According to the latest UNAIDS report, regions of North America and western and central Europe showed a 23% decline in new infections from 2010 to 2022, below the target 90% reduction.

Some regions of the United States have seen significant declines in new HIV infections. San Francisco has a 67% drop in new diagnoses. And now, along with the District of Columbia, the four states with the highest HIV rates are New York, Maryland, Georgia, and Florida.

Several countries in eastern and southern Africa are close to achieving their target HIV reduction of 90%.

Mitchell Warren, executive director of AVAC for global health advocacy, access, and equity, said that many of the low- and middle-income countries that are on track to achieve targets are able to do so because of support from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis, and Malaria.

“That foreign development assistance is transforming the AIDS response in a number of African countries, and yet at home, in various states and municipalities, not only are we not reaching that effort, we don’t even use those targets,” Mr. Warren pointed out.

“We might see municipalities that are performing well, but at a national level it’s frankly a disgrace by comparison, because we know what’s possible,” Mr. Warren said.
 

Lowering cases

Today, in the inner city of Sydney, new HIV diagnoses have plummeted by 88%, which puts the area on track to achieve the 90% UNAIDS target ahead of schedule.

Dr. Grulich and his team at the Kirby Institute are tracking new diagnoses by postal code and reported their encouraging findings here this week at the International AIDS Society Conference on HIV Science.

“This 88% decline is happening in an area where, in the ’80s and ’90s, a few thousand people died of AIDS,” Dr. Grulich told this news organization. “It feels close to miraculous.”

Dr. Grulich attributes some of the success to long-term government leadership that for the most part has been apolitical. HIV has been perceived by the public as an important health issue to be addressed. “We’ve never had a political contest over it,” he added. “We have politicians who are committed to evidence-based policy.”

In inner city Sydney, HIV prevention campaigns are a visible part of community life, Dr. Grulich explained. At public events, it is discussed; at bus stops, posters are on display; and passing trains have messages plastered to the side of them.

That community effort has consistently received government funding for years – albeit linked to key performance indicators – but it has enabled a high level of communication among government, community, clinicians, and researchers.

Another advantage is Australia’s universal health coverage, said Sharon Lewin, PhD, president of the International AIDS Society and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne. “One very clear difference for Australia is a health system that provides free medication and free prevention,” she said. “You can’t underestimate the impact that has on public health.”

Globally, significant progress has been made toward the UN’s 95-95-95 targets, with 86% of people with HIV now knowing their status, 88% of those being on treatment, and 93% of those having an undetectable viral load, “for a total of 75% of all people living with HIV worldwide with undetectable viral load,” Dr. Grulich pointed out.

But Dr. Lewin cautioned that now is not the time to take our eye off the ball, especially with respect to the 39 million or so people living with HIV globally, all of whom need lifelong treatment and care to manage their disease. “We also need to be aware that if we relax the investment, and people stop their treatment, transmission occurs again,” Dr. Lewin warned. “Despite the great news of potentially getting close to eliminating HIV transmission in Australia, HIV is far from over.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – Statins should be considered for primary prevention in people living with HIV who are at low to moderate risk of cardiovascular disease, according to final data from the REPRIEVE trial that show pitavastatin therapy is associated with a significantly lower risk of cardiovascular events than placebo.

“There was a significant 35% lower risk of major adverse cardiovascular events after a median follow-up of 5.1 years “ said Steven Grinspoon, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, who presented the final analysis of data from the REPRIEVE trial at the International AIDS Society Conference on HIV Science.

The results were simultaneously published in the New England Journal of Medicine. The primary endpoint of major adverse cardiovascular events included a composite of outcomes that included cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina, and transient ischemic attack among those treated with pitavastatin, compared with placebo (95% confidence interval, 0.48-0.90; P = .002).

The REPRIEVE trial was halted earlier this year for efficacy after an interim analysis pointed to a significantly lower rate of cardiovascular events in the treatment group.

The international double-blind, placebo-controlled trial randomly assigned 7,769 people with HIV infection, who were at low to moderate risk of cardiovascular disease, to either 4 mg daily of pitavastatin calcium or placebo.

The secondary outcome – a composite of major cardiovascular events and all-cause mortality – also showed a significant 21% reduction in risk with pitavastatin treatment, compared with placebo (95% CI, 0.65-0.96).
 

Cardiovascular events in HIV

HIV infection is an independent risk factor for cardiovascular disease, Dr. Grinspoon pointed out, and those living with HIV have about double the risk of myocardial infarction and stroke, compared with the general population.

“There’s an unmet need for people living with HIV who have low to moderate traditional risk, for whom HIV is even considered a risk equivalent but for whom no primary prevention strategy has been tested in a large trial,” Dr. Grinspoon said during an interview.

Those enrolled in the study had a 10-year Atherosclerotic Cardiovascular Disease risk score ranging from 2.1% to 7%, with a median of 4.5%. While LDL cholesterol levels at baseline ranged from 87 to 128 mg/dL, the study showed a similar reduction in cardiovascular risk regardless of LDL.

“These are types of people who, if they came to the doctor’s office right now before REPRIEVE, they would largely be told your risk score is not really making you eligible for a statin,” Dr. Grinspoon said.

He explained that what is most interesting about the reduction in risk is that it was nearly twice what would be expected with LDL lowering, based on what has previously been seen in statin trials in non–HIV-positive populations.

“I think the data are suggesting that it’s certainly in part due to the reduction in LDL – that is very important – but it’s also due to other factors beyond changes in LDL,” Dr. Grinspoon said. He speculated that the statin could be affecting anti-inflammatory and immune pathways, and that this could account for some of the reduction in cardiovascular risk, but “those data are cooking, and they’re being analyzed as we speak.”

In a substudy analysis of REPRIEVE, Markella Zanni, MD, associate professor of medicine at Harvard Medical School and Massachusetts General Hospital, focused on the women in the clinical trial.
 

Women’s risk

In REPRIEVE, 31.1% of the study population were women. Dr. Zanni and her team investigated whether there are differences in the way HIV affects the risk of developing atherosclerotic cardiovascular disease in women, compared with men.

They found that women have both higher levels of inflammatory markers, such as interleukin-6, C-reactive protein, and D-dimer, but a lower prevalence of coronary artery plaques than men.

“This finding represents an interesting paradox given that high levels of select inflammatory markers have been associated with coronary artery plaque, both among women living with HIV and among men living with HIV,” Dr. Zanni explained.

She says the researchers were hoping to further explore whether inflammation is fueling the increased risk for atherosclerotic disease, and particularly the higher risk evident in women living with HIV, compared with men.

“Women living with HIV should discuss with their treating clinicians heart risks and possible prevention strategies, including statin therapy coupled with healthy lifestyle changes addressing modifiable, traditional metabolic risk factors” she said.
 

Time for primary prevention?

All patients in the study were on antiretroviral therapy and investigators report that pitavastatin does not interact with these medications. The median CD4 cell count was 621 cells/mm³, and 87.5% of participants had an HIV viral load below the lower limit of quantification.

Participants were enrolled from 12 countries including the United States, Spain, Brazil, South Africa, and Thailand, and around two-thirds were non-White. Individuals of South Asian ethnicity showed the biggest reduction in cardiovascular risk with pitavastatin treatment.

There was a 74% higher rate of muscle pain and weakness in the pitavastatin group – affecting 91 people in the treatment arm and 53 in the placebo arm – but the majority were low grade. The rate of rhabdomyolysis of grade 3 or above was lower in the statin group, with three cases, compared with four cases in the placebo group.

Commenting on the findings, Laura Waters, MD, a genitourinary and HIV medicine consultant at Central and North West London NHS Foundation Trust’s Mortimer Market Centre, said that, while HIV infection was considered a risk factor for cardiovascular disease, risk calculators don’t specifically adjust for HIV infection.

“Now that we’ve got effective HIV drugs and people can enjoy normal life expectancy, cardiovascular disease is a particular issue for people with HIV,” she said.

Dr. Waters, who was not involved with the study, suggested that people living with HIV should discuss the use of statins with their doctor, but she acknowledged there are some barriers to treatment in people living with HIV. “It’s another pill, and when it’s a borderline [decision] it is easy to say, ‘I have to think about it,’ ” she said, with the result that statin treatment is often deferred.

The REPRIEVE study was supported by grants from the National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare. Dr. Grinspoon declared institutional grants from National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare and consultancies unrelated to the study. Dr. Zanni reports no relevant financial relationships.

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

BRISBANE, AUSTRALIA – Statins should be considered for primary prevention in people living with HIV who are at low to moderate risk of cardiovascular disease, according to final data from the REPRIEVE trial that show pitavastatin therapy is associated with a significantly lower risk of cardiovascular events than placebo.

“There was a significant 35% lower risk of major adverse cardiovascular events after a median follow-up of 5.1 years “ said Steven Grinspoon, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, who presented the final analysis of data from the REPRIEVE trial at the International AIDS Society Conference on HIV Science.

The results were simultaneously published in the New England Journal of Medicine. The primary endpoint of major adverse cardiovascular events included a composite of outcomes that included cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina, and transient ischemic attack among those treated with pitavastatin, compared with placebo (95% confidence interval, 0.48-0.90; P = .002).

The REPRIEVE trial was halted earlier this year for efficacy after an interim analysis pointed to a significantly lower rate of cardiovascular events in the treatment group.

The international double-blind, placebo-controlled trial randomly assigned 7,769 people with HIV infection, who were at low to moderate risk of cardiovascular disease, to either 4 mg daily of pitavastatin calcium or placebo.

The secondary outcome – a composite of major cardiovascular events and all-cause mortality – also showed a significant 21% reduction in risk with pitavastatin treatment, compared with placebo (95% CI, 0.65-0.96).
 

Cardiovascular events in HIV

HIV infection is an independent risk factor for cardiovascular disease, Dr. Grinspoon pointed out, and those living with HIV have about double the risk of myocardial infarction and stroke, compared with the general population.

“There’s an unmet need for people living with HIV who have low to moderate traditional risk, for whom HIV is even considered a risk equivalent but for whom no primary prevention strategy has been tested in a large trial,” Dr. Grinspoon said during an interview.

Those enrolled in the study had a 10-year Atherosclerotic Cardiovascular Disease risk score ranging from 2.1% to 7%, with a median of 4.5%. While LDL cholesterol levels at baseline ranged from 87 to 128 mg/dL, the study showed a similar reduction in cardiovascular risk regardless of LDL.

“These are types of people who, if they came to the doctor’s office right now before REPRIEVE, they would largely be told your risk score is not really making you eligible for a statin,” Dr. Grinspoon said.

He explained that what is most interesting about the reduction in risk is that it was nearly twice what would be expected with LDL lowering, based on what has previously been seen in statin trials in non–HIV-positive populations.

“I think the data are suggesting that it’s certainly in part due to the reduction in LDL – that is very important – but it’s also due to other factors beyond changes in LDL,” Dr. Grinspoon said. He speculated that the statin could be affecting anti-inflammatory and immune pathways, and that this could account for some of the reduction in cardiovascular risk, but “those data are cooking, and they’re being analyzed as we speak.”

In a substudy analysis of REPRIEVE, Markella Zanni, MD, associate professor of medicine at Harvard Medical School and Massachusetts General Hospital, focused on the women in the clinical trial.
 

Women’s risk

In REPRIEVE, 31.1% of the study population were women. Dr. Zanni and her team investigated whether there are differences in the way HIV affects the risk of developing atherosclerotic cardiovascular disease in women, compared with men.

They found that women have both higher levels of inflammatory markers, such as interleukin-6, C-reactive protein, and D-dimer, but a lower prevalence of coronary artery plaques than men.

“This finding represents an interesting paradox given that high levels of select inflammatory markers have been associated with coronary artery plaque, both among women living with HIV and among men living with HIV,” Dr. Zanni explained.

She says the researchers were hoping to further explore whether inflammation is fueling the increased risk for atherosclerotic disease, and particularly the higher risk evident in women living with HIV, compared with men.

“Women living with HIV should discuss with their treating clinicians heart risks and possible prevention strategies, including statin therapy coupled with healthy lifestyle changes addressing modifiable, traditional metabolic risk factors” she said.
 

Time for primary prevention?

All patients in the study were on antiretroviral therapy and investigators report that pitavastatin does not interact with these medications. The median CD4 cell count was 621 cells/mm³, and 87.5% of participants had an HIV viral load below the lower limit of quantification.

Participants were enrolled from 12 countries including the United States, Spain, Brazil, South Africa, and Thailand, and around two-thirds were non-White. Individuals of South Asian ethnicity showed the biggest reduction in cardiovascular risk with pitavastatin treatment.

There was a 74% higher rate of muscle pain and weakness in the pitavastatin group – affecting 91 people in the treatment arm and 53 in the placebo arm – but the majority were low grade. The rate of rhabdomyolysis of grade 3 or above was lower in the statin group, with three cases, compared with four cases in the placebo group.

Commenting on the findings, Laura Waters, MD, a genitourinary and HIV medicine consultant at Central and North West London NHS Foundation Trust’s Mortimer Market Centre, said that, while HIV infection was considered a risk factor for cardiovascular disease, risk calculators don’t specifically adjust for HIV infection.

“Now that we’ve got effective HIV drugs and people can enjoy normal life expectancy, cardiovascular disease is a particular issue for people with HIV,” she said.

Dr. Waters, who was not involved with the study, suggested that people living with HIV should discuss the use of statins with their doctor, but she acknowledged there are some barriers to treatment in people living with HIV. “It’s another pill, and when it’s a borderline [decision] it is easy to say, ‘I have to think about it,’ ” she said, with the result that statin treatment is often deferred.

The REPRIEVE study was supported by grants from the National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare. Dr. Grinspoon declared institutional grants from National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare and consultancies unrelated to the study. Dr. Zanni reports no relevant financial relationships.

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

BRISBANE, AUSTRALIA – Statins should be considered for primary prevention in people living with HIV who are at low to moderate risk of cardiovascular disease, according to final data from the REPRIEVE trial that show pitavastatin therapy is associated with a significantly lower risk of cardiovascular events than placebo.

“There was a significant 35% lower risk of major adverse cardiovascular events after a median follow-up of 5.1 years “ said Steven Grinspoon, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, who presented the final analysis of data from the REPRIEVE trial at the International AIDS Society Conference on HIV Science.

The results were simultaneously published in the New England Journal of Medicine. The primary endpoint of major adverse cardiovascular events included a composite of outcomes that included cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina, and transient ischemic attack among those treated with pitavastatin, compared with placebo (95% confidence interval, 0.48-0.90; P = .002).

The REPRIEVE trial was halted earlier this year for efficacy after an interim analysis pointed to a significantly lower rate of cardiovascular events in the treatment group.

The international double-blind, placebo-controlled trial randomly assigned 7,769 people with HIV infection, who were at low to moderate risk of cardiovascular disease, to either 4 mg daily of pitavastatin calcium or placebo.

The secondary outcome – a composite of major cardiovascular events and all-cause mortality – also showed a significant 21% reduction in risk with pitavastatin treatment, compared with placebo (95% CI, 0.65-0.96).
 

Cardiovascular events in HIV

HIV infection is an independent risk factor for cardiovascular disease, Dr. Grinspoon pointed out, and those living with HIV have about double the risk of myocardial infarction and stroke, compared with the general population.

“There’s an unmet need for people living with HIV who have low to moderate traditional risk, for whom HIV is even considered a risk equivalent but for whom no primary prevention strategy has been tested in a large trial,” Dr. Grinspoon said during an interview.

Those enrolled in the study had a 10-year Atherosclerotic Cardiovascular Disease risk score ranging from 2.1% to 7%, with a median of 4.5%. While LDL cholesterol levels at baseline ranged from 87 to 128 mg/dL, the study showed a similar reduction in cardiovascular risk regardless of LDL.

“These are types of people who, if they came to the doctor’s office right now before REPRIEVE, they would largely be told your risk score is not really making you eligible for a statin,” Dr. Grinspoon said.

He explained that what is most interesting about the reduction in risk is that it was nearly twice what would be expected with LDL lowering, based on what has previously been seen in statin trials in non–HIV-positive populations.

“I think the data are suggesting that it’s certainly in part due to the reduction in LDL – that is very important – but it’s also due to other factors beyond changes in LDL,” Dr. Grinspoon said. He speculated that the statin could be affecting anti-inflammatory and immune pathways, and that this could account for some of the reduction in cardiovascular risk, but “those data are cooking, and they’re being analyzed as we speak.”

In a substudy analysis of REPRIEVE, Markella Zanni, MD, associate professor of medicine at Harvard Medical School and Massachusetts General Hospital, focused on the women in the clinical trial.
 

Women’s risk

In REPRIEVE, 31.1% of the study population were women. Dr. Zanni and her team investigated whether there are differences in the way HIV affects the risk of developing atherosclerotic cardiovascular disease in women, compared with men.

They found that women have both higher levels of inflammatory markers, such as interleukin-6, C-reactive protein, and D-dimer, but a lower prevalence of coronary artery plaques than men.

“This finding represents an interesting paradox given that high levels of select inflammatory markers have been associated with coronary artery plaque, both among women living with HIV and among men living with HIV,” Dr. Zanni explained.

She says the researchers were hoping to further explore whether inflammation is fueling the increased risk for atherosclerotic disease, and particularly the higher risk evident in women living with HIV, compared with men.

“Women living with HIV should discuss with their treating clinicians heart risks and possible prevention strategies, including statin therapy coupled with healthy lifestyle changes addressing modifiable, traditional metabolic risk factors” she said.
 

Time for primary prevention?

All patients in the study were on antiretroviral therapy and investigators report that pitavastatin does not interact with these medications. The median CD4 cell count was 621 cells/mm³, and 87.5% of participants had an HIV viral load below the lower limit of quantification.

Participants were enrolled from 12 countries including the United States, Spain, Brazil, South Africa, and Thailand, and around two-thirds were non-White. Individuals of South Asian ethnicity showed the biggest reduction in cardiovascular risk with pitavastatin treatment.

There was a 74% higher rate of muscle pain and weakness in the pitavastatin group – affecting 91 people in the treatment arm and 53 in the placebo arm – but the majority were low grade. The rate of rhabdomyolysis of grade 3 or above was lower in the statin group, with three cases, compared with four cases in the placebo group.

Commenting on the findings, Laura Waters, MD, a genitourinary and HIV medicine consultant at Central and North West London NHS Foundation Trust’s Mortimer Market Centre, said that, while HIV infection was considered a risk factor for cardiovascular disease, risk calculators don’t specifically adjust for HIV infection.

“Now that we’ve got effective HIV drugs and people can enjoy normal life expectancy, cardiovascular disease is a particular issue for people with HIV,” she said.

Dr. Waters, who was not involved with the study, suggested that people living with HIV should discuss the use of statins with their doctor, but she acknowledged there are some barriers to treatment in people living with HIV. “It’s another pill, and when it’s a borderline [decision] it is easy to say, ‘I have to think about it,’ ” she said, with the result that statin treatment is often deferred.

The REPRIEVE study was supported by grants from the National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare. Dr. Grinspoon declared institutional grants from National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare and consultancies unrelated to the study. Dr. Zanni reports no relevant financial relationships.

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

Chronic pulmonary disease continues to be a major cause of morbidity and mortality in individuals living with the human immunodeficiency virus, even with optimal HIV control. And this is independent, as seen in many studies, of age, smoking, and pulmonary infections.

Both chronic pulmonary obstructive disease (COPD) and lung cancer occur more frequently in people living with HIV than in the general population, and at earlier ages, and with worse outcomes. The risk for emphysema and interstitial lung abnormalities also appears to be higher, research has shown. And asthma has also recently emerged as another important lung disease in people with HIV (PWH).

“There is evidence that the severity of immunocompromise associated with HIV infection is linked with chronic lung diseases. People who have a lower CD4 cell count or a higher viral load do have an increased risk of COPD and emphysema as well as potentially lung cancer. But [while] immunocompromise plays a role, it isn’t the only story, given that even with well-controlled HIV there is increased risk,” said Kristina Crothers, MD, professor in the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle.

Research has evolved from a focus on the epidemiology of HIV-related chronic lung diseases to a current emphasis on “trying to understand further the mechanisms [behind the heightened risk] through more benchwork and corollary translational studies, and then to the next level of trying to understand what this means for how we should manage people with HIV who have chronic lung diseases,” Dr. Crothers said. “Should management be tailored for people with HIV infection?”

Impairments in immune pathways, local and systemic inflammation, oxidative stress, dysbiosis, and accelerated cellular senescence are among potential mechanisms, but until ongoing mechanistic research yields more answers, pulmonologists should simply – but importantly – be aware of the increased risk and have a low threshold for investigating respiratory symptoms, she and other experts said in interviews. Referral of eligible patients for lung cancer screening is also a priority, as is smoking cessation, they said.

Notably, while spirometry has been the most commonly studied lung function measure in PWH, another noninvasive measure, diffusing capacity for carbon monoxide (DLCO), has garnered attention in the past decade and thus far appears to be the more frequent lung function abnormality.

In an analysis published in 2020 from the longitudinal Multicenter AIDS Cohort Study (MACS) – a study of a subcohort of 591 men with HIV and 476 without HIV – those with HIV were found to have a 1.6-fold increased risk of mild DLCO impairment (< 80% of predicted normal) and a 3-fold higher risk of more severe DLCO impairment (< 60% of predicted normal). There was no significant difference in spirometry findings by HIV status.

Such findings on DLCO are worthy of consideration in clinical practice, even in the absence of HIV-specific screening guidelines for noncommunicable lung diseases, Dr. Crothers said. “In thinking about screening and diagnosing chronic lung diseases in these patients, I’d not only consider spirometry, but also diffusing capacity” when possible, she said. Impaired DLCO is seen with emphysema and pulmonary vascular diseases like pulmonary hypertension and also interstitial lung diseases.
 

Key chronic lung diseases

Ken M. Kunisaki, MD, MS, associate professor of medicine at the University of Minnesota, Minneapolis, and the first author of the MACS analysis of lung function – one of the most recent and largest reports of DLCO impairment – points out that studies of chest computed tomography (CT) have also documented higher rates of emphysema and interstitial lung abnormalities.

A chest CT analysis from a cohort in Denmark (the Copenhagen Comorbidity in HIV Infection [COCOMO] cohort) found interstitial lung abnormalities in 10.9% of more than 700 PWH which represented a 1.8-fold increased risk compared to HIV-negative controls. And a study from an Italian sample of never-smoking PWH and controls reported emphysema in 18% and 4%, respectively. These studies, which did not measure DLCO, are among those discussed in a 2021 review by Dr. Kunisaki of advances in HIV-associated chronic lung disease research.

COPD is the best studied and most commonly encountered chronic lung disease in PWH. “Particularly for COPD, what’s both interesting and unfortunate is that we haven’t really seen any changes in the epidemiology with ART (antiretroviral therapy) – we’re still seeing the same findings, like the association of HIV with worse COPD at younger ages,” said Alison Morris, MD, MS, professor of medicine, immunology, and clinical and translational research at the University of Pittsburgh. “It doesn’t seem to have improved.”

Its prevalence has varied widely from cohort to cohort, from as low as 3% (similar to the general population) to over 40%, Dr. Kunisaki said, emphasizing that many studies, including studies showing higher rates, have controlled for current and past smoking. In evaluating patients with low or no smoking burden, “don’t discount respiratory symptoms as possibly reflecting underlying lung disease because COPD can develop with low to no smoking history in those with HIV,” he advised.

A better understanding of how a chronic viral infection like HIV leads to heightened COPD risk will not only help those with HIV, he notes, but also people without HIV who have COPD but have never smoked – a woefully underappreciated and understudied population. Ongoing research, he said, “should help us understand COPD pathogenesis generally.”

Research on asthma is relatively limited thus far, but it does appear that PWH may be more prone to developing severe asthma, just as with COPD, said Dr. Kunisaki, also a staff physician at the Minneapolis Veterans Administration Health Care System. Research has shown, for instance, that people with HIV more frequently needed aggressive respiratory support when hospitalized for asthma exacerbations.

It’s unclear how much of this potentially increased severity is attributable to the biology of HIV’s impact on the body and how much relates to social factors like disparities in income and access to care, Dr. Kunisaki said, noting that the same questions apply to the more frequent COPD exacerbations documented in PWH.

Dr. Crothers points out that, while most studies do not suggest a difference in the incidence of asthma in PWH, “there is some data from researchers looking at asthma profiles [suggesting] that the biomarkers associated with asthma may be different in people with and without HIV,” signaling potentially different molecular or biologic underpinnings of the disease.

Incidence rates of lung cancer in PWH, meanwhile, have declined over the last 2 decades, but lung cancer remains the leading cause of cancer-related mortality in PWH and occurs at a rate that is 2-2.5 times higher than that of individuals not infected with HIV, according to

Janice Leung, MD, of the division of respiratory medicine at the University of British Columbia and the Centre for Heart Lung Innovation at St. Paul’s Hospital in Vancouver.

Patients with HIV have “worse outcomes overall and a higher risk of mortality, even when presenting at the same stage,” said Dr. Leung, who reviewed trends in COPD and lung cancer in a recently published opinion piece.
 

Potential drivers

A bird’s eye view of potential – and likely interrelated – mechanisms for chronic lung disease includes chronic immune activation that impairs innate and adaptive immune pathways; chronic inflammation systemically and in the lung despite viral suppression; persistence of the virus in latent reservoirs in the lung, particularly in alveolar macrophages and T cells; HIV-related proteins contributing to oxidative stress; accelerated cellular aging; dysbiosis; and ongoing injury from inhaled toxins.

All are described in the literature and are being further explored. “It’s likely that multiple pathways are playing a role,” said Dr. Crothers, “and it could be that the balance of one to another leads to different manifestations of disease.”

Biomarkers that have been elevated and associated with different features of chronic lung disease – such as airflow obstruction, low DLCO, and emphysema – include markers of inflammation (e.g., C-reactive protein, interleukin-6), monocyte activation (e.g., soluble CD14), and markers of endothelial dysfunction, she noted in a 2021 commentary marking 40 years since the first reported cases of acquired immunodeficiency syndrome.

In her laboratory, Dr. Leung is using new epigenetic markers to look at the pathogenesis of accelerated aging in the lung. By profiling bronchial epithelial brushings for DNA methylation and gene expression, they have found that “people living with both HIV and COPD have the fastest epigenetic age acceleration in their airway epithelium,” she said. The findings “suggest that the HIV lung is aging faster.”

They reported their findings in 2022, describing methylation disruptions along age-related pathways such as cellular senescence, longevity regulation, and insulin signaling.

Dr. Leung and her team have also studied the lung microbiome and found lower microbial diversity in the airway epithelium in patients with HIV than those without, especially in those with HIV and COPD. The National Institutes of Health–sponsored Lung HIV Microbiome Project found that changes in the lung microbiome are most pronounced in patients who haven’t yet initiated ART, but research in her lab suggests ongoing suppression of microbial diversity even after ART, she said.

Dr. Morris is particularly interested in the oral microbiome, having found through her research that changes in the oral microbiome in PWH were more related to impaired lung function than alterations in the lung and gut microbiome. “That may be in part because of the way we measure things,” she said. “But we also think that the oral microbiome probably seeds the lung [through micro-aspiration].” A study published in 2020 from the Pittsburgh site of the MACS described alterations in oral microbial communities in PWH with abnormal lung function.

Preliminary research suggests that improved dental cleaning and periodontal work in PWH and COPD may influence the severity of COPD, she noted.

“We don’t see as much of a signal with the gut microbiome [and HIV status or lung function], though there could still be ways in which gut microbiome influences the lung,” through systemic inflammation, the release of metabolites into the bloodstream, or microbial translocation, for instance, she said.

The potential role of translocation of members of the microbiome, in fact, is an area of active research for Dr. Morris. Members of the microbiome – viruses and fungi in addition to bacteria – “can get into the bloodstream from the mouth, from the lung, from the gut, to stimulate inflammation and worsen lung disease,” she said.
 

Key questions in an evolving research landscape

Dr. Kunisaki looks forward to research providing a more longitudinal look at lung function decline– a move beyond a dominance of cross-sectional studies – as well as research that is more comprehensive, with simultaneous collection of various functional measures (eg., DLCO with chest imaging and fractional excretion of nitric oxide (FENO – a standardized breath measure of Th2 airway inflammation).

The several-year-old NIH-supported MACS/WIHS (Women’s Interagency HIV Study) Combined Cohort study, in which Dr. Kunisaki and Dr. Morris participate, aims in part to identity biomarkers of increased risk for chronic lung disease and other chronic disorders and to develop strategies for more effective interventions and treatments.

Researchers will also share biospecimens, “which will allow more mechanistic work,” Dr. Kunisaki noted. (The combined cohort study includes participants from the earlier, separate MACS and WIHS studies.)

Questions about treatment strategies include the risks versus benefits of inhaled corticosteroids, which may increase an already elevated risk of respiratory infections like bacterial pneumonia in PWH, Dr. Kunisaki said.

[An aside: Inhaled corticosteroids also have well-described interactions with ART regimens that contain CYP3A4 inhibitors (e.g., ritonavir and cobicistat) that can lead to hypercortisolism. In patients who require both types of drugs, he said, beclomethasone has the least interactions and is the preferred inhaled corticosteroid.]

For Dr. Crothers, unanswered critical questions include – as she wrote in her 2021 commentary – the question of how guidelines for the management of COPD and asthma should be adapted for PWH. Is COPD in PWH more or less responsive to inhaled corticosteroids, for instance? And are antifibrotic treatments for interstitial lung disease and immunotherapies for asthma or lung cancer similarly effective, and are there any increased risks for harms in people with HIV?

There’s also the question of whether PWH should be screened for lung cancer earlier and with a lower smoking exposure than is advised under current guidelines for the general population, she said in the interview. “And should the approach to shared decision-making be modified for people with HIV?” she said. “We’re doing some work on these questions” right now.

None of the researchers interviewed reported any conflicts of interest relevant to the story. Dr. Kunisaki reported that he has no relevant disclosures, and said that his comments are his personal views and not official views of the U.S. Government, Department of Veterans Affairs, the Minneapolis VA, or the University of Minnesota.

Chronic pulmonary disease continues to be a major cause of morbidity and mortality in individuals living with the human immunodeficiency virus, even with optimal HIV control. And this is independent, as seen in many studies, of age, smoking, and pulmonary infections.

Both chronic pulmonary obstructive disease (COPD) and lung cancer occur more frequently in people living with HIV than in the general population, and at earlier ages, and with worse outcomes. The risk for emphysema and interstitial lung abnormalities also appears to be higher, research has shown. And asthma has also recently emerged as another important lung disease in people with HIV (PWH).

“There is evidence that the severity of immunocompromise associated with HIV infection is linked with chronic lung diseases. People who have a lower CD4 cell count or a higher viral load do have an increased risk of COPD and emphysema as well as potentially lung cancer. But [while] immunocompromise plays a role, it isn’t the only story, given that even with well-controlled HIV there is increased risk,” said Kristina Crothers, MD, professor in the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle.

Research has evolved from a focus on the epidemiology of HIV-related chronic lung diseases to a current emphasis on “trying to understand further the mechanisms [behind the heightened risk] through more benchwork and corollary translational studies, and then to the next level of trying to understand what this means for how we should manage people with HIV who have chronic lung diseases,” Dr. Crothers said. “Should management be tailored for people with HIV infection?”

Impairments in immune pathways, local and systemic inflammation, oxidative stress, dysbiosis, and accelerated cellular senescence are among potential mechanisms, but until ongoing mechanistic research yields more answers, pulmonologists should simply – but importantly – be aware of the increased risk and have a low threshold for investigating respiratory symptoms, she and other experts said in interviews. Referral of eligible patients for lung cancer screening is also a priority, as is smoking cessation, they said.

Notably, while spirometry has been the most commonly studied lung function measure in PWH, another noninvasive measure, diffusing capacity for carbon monoxide (DLCO), has garnered attention in the past decade and thus far appears to be the more frequent lung function abnormality.

In an analysis published in 2020 from the longitudinal Multicenter AIDS Cohort Study (MACS) – a study of a subcohort of 591 men with HIV and 476 without HIV – those with HIV were found to have a 1.6-fold increased risk of mild DLCO impairment (< 80% of predicted normal) and a 3-fold higher risk of more severe DLCO impairment (< 60% of predicted normal). There was no significant difference in spirometry findings by HIV status.

Such findings on DLCO are worthy of consideration in clinical practice, even in the absence of HIV-specific screening guidelines for noncommunicable lung diseases, Dr. Crothers said. “In thinking about screening and diagnosing chronic lung diseases in these patients, I’d not only consider spirometry, but also diffusing capacity” when possible, she said. Impaired DLCO is seen with emphysema and pulmonary vascular diseases like pulmonary hypertension and also interstitial lung diseases.
 

Key chronic lung diseases

Ken M. Kunisaki, MD, MS, associate professor of medicine at the University of Minnesota, Minneapolis, and the first author of the MACS analysis of lung function – one of the most recent and largest reports of DLCO impairment – points out that studies of chest computed tomography (CT) have also documented higher rates of emphysema and interstitial lung abnormalities.

A chest CT analysis from a cohort in Denmark (the Copenhagen Comorbidity in HIV Infection [COCOMO] cohort) found interstitial lung abnormalities in 10.9% of more than 700 PWH which represented a 1.8-fold increased risk compared to HIV-negative controls. And a study from an Italian sample of never-smoking PWH and controls reported emphysema in 18% and 4%, respectively. These studies, which did not measure DLCO, are among those discussed in a 2021 review by Dr. Kunisaki of advances in HIV-associated chronic lung disease research.

COPD is the best studied and most commonly encountered chronic lung disease in PWH. “Particularly for COPD, what’s both interesting and unfortunate is that we haven’t really seen any changes in the epidemiology with ART (antiretroviral therapy) – we’re still seeing the same findings, like the association of HIV with worse COPD at younger ages,” said Alison Morris, MD, MS, professor of medicine, immunology, and clinical and translational research at the University of Pittsburgh. “It doesn’t seem to have improved.”

Its prevalence has varied widely from cohort to cohort, from as low as 3% (similar to the general population) to over 40%, Dr. Kunisaki said, emphasizing that many studies, including studies showing higher rates, have controlled for current and past smoking. In evaluating patients with low or no smoking burden, “don’t discount respiratory symptoms as possibly reflecting underlying lung disease because COPD can develop with low to no smoking history in those with HIV,” he advised.

A better understanding of how a chronic viral infection like HIV leads to heightened COPD risk will not only help those with HIV, he notes, but also people without HIV who have COPD but have never smoked – a woefully underappreciated and understudied population. Ongoing research, he said, “should help us understand COPD pathogenesis generally.”

Research on asthma is relatively limited thus far, but it does appear that PWH may be more prone to developing severe asthma, just as with COPD, said Dr. Kunisaki, also a staff physician at the Minneapolis Veterans Administration Health Care System. Research has shown, for instance, that people with HIV more frequently needed aggressive respiratory support when hospitalized for asthma exacerbations.

It’s unclear how much of this potentially increased severity is attributable to the biology of HIV’s impact on the body and how much relates to social factors like disparities in income and access to care, Dr. Kunisaki said, noting that the same questions apply to the more frequent COPD exacerbations documented in PWH.

Dr. Crothers points out that, while most studies do not suggest a difference in the incidence of asthma in PWH, “there is some data from researchers looking at asthma profiles [suggesting] that the biomarkers associated with asthma may be different in people with and without HIV,” signaling potentially different molecular or biologic underpinnings of the disease.

Incidence rates of lung cancer in PWH, meanwhile, have declined over the last 2 decades, but lung cancer remains the leading cause of cancer-related mortality in PWH and occurs at a rate that is 2-2.5 times higher than that of individuals not infected with HIV, according to

Janice Leung, MD, of the division of respiratory medicine at the University of British Columbia and the Centre for Heart Lung Innovation at St. Paul’s Hospital in Vancouver.

Patients with HIV have “worse outcomes overall and a higher risk of mortality, even when presenting at the same stage,” said Dr. Leung, who reviewed trends in COPD and lung cancer in a recently published opinion piece.
 

Potential drivers

A bird’s eye view of potential – and likely interrelated – mechanisms for chronic lung disease includes chronic immune activation that impairs innate and adaptive immune pathways; chronic inflammation systemically and in the lung despite viral suppression; persistence of the virus in latent reservoirs in the lung, particularly in alveolar macrophages and T cells; HIV-related proteins contributing to oxidative stress; accelerated cellular aging; dysbiosis; and ongoing injury from inhaled toxins.

All are described in the literature and are being further explored. “It’s likely that multiple pathways are playing a role,” said Dr. Crothers, “and it could be that the balance of one to another leads to different manifestations of disease.”

Biomarkers that have been elevated and associated with different features of chronic lung disease – such as airflow obstruction, low DLCO, and emphysema – include markers of inflammation (e.g., C-reactive protein, interleukin-6), monocyte activation (e.g., soluble CD14), and markers of endothelial dysfunction, she noted in a 2021 commentary marking 40 years since the first reported cases of acquired immunodeficiency syndrome.

In her laboratory, Dr. Leung is using new epigenetic markers to look at the pathogenesis of accelerated aging in the lung. By profiling bronchial epithelial brushings for DNA methylation and gene expression, they have found that “people living with both HIV and COPD have the fastest epigenetic age acceleration in their airway epithelium,” she said. The findings “suggest that the HIV lung is aging faster.”

They reported their findings in 2022, describing methylation disruptions along age-related pathways such as cellular senescence, longevity regulation, and insulin signaling.

Dr. Leung and her team have also studied the lung microbiome and found lower microbial diversity in the airway epithelium in patients with HIV than those without, especially in those with HIV and COPD. The National Institutes of Health–sponsored Lung HIV Microbiome Project found that changes in the lung microbiome are most pronounced in patients who haven’t yet initiated ART, but research in her lab suggests ongoing suppression of microbial diversity even after ART, she said.

Dr. Morris is particularly interested in the oral microbiome, having found through her research that changes in the oral microbiome in PWH were more related to impaired lung function than alterations in the lung and gut microbiome. “That may be in part because of the way we measure things,” she said. “But we also think that the oral microbiome probably seeds the lung [through micro-aspiration].” A study published in 2020 from the Pittsburgh site of the MACS described alterations in oral microbial communities in PWH with abnormal lung function.

Preliminary research suggests that improved dental cleaning and periodontal work in PWH and COPD may influence the severity of COPD, she noted.

“We don’t see as much of a signal with the gut microbiome [and HIV status or lung function], though there could still be ways in which gut microbiome influences the lung,” through systemic inflammation, the release of metabolites into the bloodstream, or microbial translocation, for instance, she said.

The potential role of translocation of members of the microbiome, in fact, is an area of active research for Dr. Morris. Members of the microbiome – viruses and fungi in addition to bacteria – “can get into the bloodstream from the mouth, from the lung, from the gut, to stimulate inflammation and worsen lung disease,” she said.
 

Key questions in an evolving research landscape

Dr. Kunisaki looks forward to research providing a more longitudinal look at lung function decline– a move beyond a dominance of cross-sectional studies – as well as research that is more comprehensive, with simultaneous collection of various functional measures (eg., DLCO with chest imaging and fractional excretion of nitric oxide (FENO – a standardized breath measure of Th2 airway inflammation).

The several-year-old NIH-supported MACS/WIHS (Women’s Interagency HIV Study) Combined Cohort study, in which Dr. Kunisaki and Dr. Morris participate, aims in part to identity biomarkers of increased risk for chronic lung disease and other chronic disorders and to develop strategies for more effective interventions and treatments.

Researchers will also share biospecimens, “which will allow more mechanistic work,” Dr. Kunisaki noted. (The combined cohort study includes participants from the earlier, separate MACS and WIHS studies.)

Questions about treatment strategies include the risks versus benefits of inhaled corticosteroids, which may increase an already elevated risk of respiratory infections like bacterial pneumonia in PWH, Dr. Kunisaki said.

[An aside: Inhaled corticosteroids also have well-described interactions with ART regimens that contain CYP3A4 inhibitors (e.g., ritonavir and cobicistat) that can lead to hypercortisolism. In patients who require both types of drugs, he said, beclomethasone has the least interactions and is the preferred inhaled corticosteroid.]

For Dr. Crothers, unanswered critical questions include – as she wrote in her 2021 commentary – the question of how guidelines for the management of COPD and asthma should be adapted for PWH. Is COPD in PWH more or less responsive to inhaled corticosteroids, for instance? And are antifibrotic treatments for interstitial lung disease and immunotherapies for asthma or lung cancer similarly effective, and are there any increased risks for harms in people with HIV?

There’s also the question of whether PWH should be screened for lung cancer earlier and with a lower smoking exposure than is advised under current guidelines for the general population, she said in the interview. “And should the approach to shared decision-making be modified for people with HIV?” she said. “We’re doing some work on these questions” right now.

None of the researchers interviewed reported any conflicts of interest relevant to the story. Dr. Kunisaki reported that he has no relevant disclosures, and said that his comments are his personal views and not official views of the U.S. Government, Department of Veterans Affairs, the Minneapolis VA, or the University of Minnesota.

Chronic pulmonary disease continues to be a major cause of morbidity and mortality in individuals living with the human immunodeficiency virus, even with optimal HIV control. And this is independent, as seen in many studies, of age, smoking, and pulmonary infections.

Both chronic pulmonary obstructive disease (COPD) and lung cancer occur more frequently in people living with HIV than in the general population, and at earlier ages, and with worse outcomes. The risk for emphysema and interstitial lung abnormalities also appears to be higher, research has shown. And asthma has also recently emerged as another important lung disease in people with HIV (PWH).

“There is evidence that the severity of immunocompromise associated with HIV infection is linked with chronic lung diseases. People who have a lower CD4 cell count or a higher viral load do have an increased risk of COPD and emphysema as well as potentially lung cancer. But [while] immunocompromise plays a role, it isn’t the only story, given that even with well-controlled HIV there is increased risk,” said Kristina Crothers, MD, professor in the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle.

Research has evolved from a focus on the epidemiology of HIV-related chronic lung diseases to a current emphasis on “trying to understand further the mechanisms [behind the heightened risk] through more benchwork and corollary translational studies, and then to the next level of trying to understand what this means for how we should manage people with HIV who have chronic lung diseases,” Dr. Crothers said. “Should management be tailored for people with HIV infection?”

Impairments in immune pathways, local and systemic inflammation, oxidative stress, dysbiosis, and accelerated cellular senescence are among potential mechanisms, but until ongoing mechanistic research yields more answers, pulmonologists should simply – but importantly – be aware of the increased risk and have a low threshold for investigating respiratory symptoms, she and other experts said in interviews. Referral of eligible patients for lung cancer screening is also a priority, as is smoking cessation, they said.

Notably, while spirometry has been the most commonly studied lung function measure in PWH, another noninvasive measure, diffusing capacity for carbon monoxide (DLCO), has garnered attention in the past decade and thus far appears to be the more frequent lung function abnormality.

In an analysis published in 2020 from the longitudinal Multicenter AIDS Cohort Study (MACS) – a study of a subcohort of 591 men with HIV and 476 without HIV – those with HIV were found to have a 1.6-fold increased risk of mild DLCO impairment (< 80% of predicted normal) and a 3-fold higher risk of more severe DLCO impairment (< 60% of predicted normal). There was no significant difference in spirometry findings by HIV status.

Such findings on DLCO are worthy of consideration in clinical practice, even in the absence of HIV-specific screening guidelines for noncommunicable lung diseases, Dr. Crothers said. “In thinking about screening and diagnosing chronic lung diseases in these patients, I’d not only consider spirometry, but also diffusing capacity” when possible, she said. Impaired DLCO is seen with emphysema and pulmonary vascular diseases like pulmonary hypertension and also interstitial lung diseases.
 

Key chronic lung diseases

Ken M. Kunisaki, MD, MS, associate professor of medicine at the University of Minnesota, Minneapolis, and the first author of the MACS analysis of lung function – one of the most recent and largest reports of DLCO impairment – points out that studies of chest computed tomography (CT) have also documented higher rates of emphysema and interstitial lung abnormalities.

A chest CT analysis from a cohort in Denmark (the Copenhagen Comorbidity in HIV Infection [COCOMO] cohort) found interstitial lung abnormalities in 10.9% of more than 700 PWH which represented a 1.8-fold increased risk compared to HIV-negative controls. And a study from an Italian sample of never-smoking PWH and controls reported emphysema in 18% and 4%, respectively. These studies, which did not measure DLCO, are among those discussed in a 2021 review by Dr. Kunisaki of advances in HIV-associated chronic lung disease research.

COPD is the best studied and most commonly encountered chronic lung disease in PWH. “Particularly for COPD, what’s both interesting and unfortunate is that we haven’t really seen any changes in the epidemiology with ART (antiretroviral therapy) – we’re still seeing the same findings, like the association of HIV with worse COPD at younger ages,” said Alison Morris, MD, MS, professor of medicine, immunology, and clinical and translational research at the University of Pittsburgh. “It doesn’t seem to have improved.”

Its prevalence has varied widely from cohort to cohort, from as low as 3% (similar to the general population) to over 40%, Dr. Kunisaki said, emphasizing that many studies, including studies showing higher rates, have controlled for current and past smoking. In evaluating patients with low or no smoking burden, “don’t discount respiratory symptoms as possibly reflecting underlying lung disease because COPD can develop with low to no smoking history in those with HIV,” he advised.

A better understanding of how a chronic viral infection like HIV leads to heightened COPD risk will not only help those with HIV, he notes, but also people without HIV who have COPD but have never smoked – a woefully underappreciated and understudied population. Ongoing research, he said, “should help us understand COPD pathogenesis generally.”

Research on asthma is relatively limited thus far, but it does appear that PWH may be more prone to developing severe asthma, just as with COPD, said Dr. Kunisaki, also a staff physician at the Minneapolis Veterans Administration Health Care System. Research has shown, for instance, that people with HIV more frequently needed aggressive respiratory support when hospitalized for asthma exacerbations.

It’s unclear how much of this potentially increased severity is attributable to the biology of HIV’s impact on the body and how much relates to social factors like disparities in income and access to care, Dr. Kunisaki said, noting that the same questions apply to the more frequent COPD exacerbations documented in PWH.

Dr. Crothers points out that, while most studies do not suggest a difference in the incidence of asthma in PWH, “there is some data from researchers looking at asthma profiles [suggesting] that the biomarkers associated with asthma may be different in people with and without HIV,” signaling potentially different molecular or biologic underpinnings of the disease.

Incidence rates of lung cancer in PWH, meanwhile, have declined over the last 2 decades, but lung cancer remains the leading cause of cancer-related mortality in PWH and occurs at a rate that is 2-2.5 times higher than that of individuals not infected with HIV, according to

Janice Leung, MD, of the division of respiratory medicine at the University of British Columbia and the Centre for Heart Lung Innovation at St. Paul’s Hospital in Vancouver.

Patients with HIV have “worse outcomes overall and a higher risk of mortality, even when presenting at the same stage,” said Dr. Leung, who reviewed trends in COPD and lung cancer in a recently published opinion piece.
 

Potential drivers

A bird’s eye view of potential – and likely interrelated – mechanisms for chronic lung disease includes chronic immune activation that impairs innate and adaptive immune pathways; chronic inflammation systemically and in the lung despite viral suppression; persistence of the virus in latent reservoirs in the lung, particularly in alveolar macrophages and T cells; HIV-related proteins contributing to oxidative stress; accelerated cellular aging; dysbiosis; and ongoing injury from inhaled toxins.

All are described in the literature and are being further explored. “It’s likely that multiple pathways are playing a role,” said Dr. Crothers, “and it could be that the balance of one to another leads to different manifestations of disease.”

Biomarkers that have been elevated and associated with different features of chronic lung disease – such as airflow obstruction, low DLCO, and emphysema – include markers of inflammation (e.g., C-reactive protein, interleukin-6), monocyte activation (e.g., soluble CD14), and markers of endothelial dysfunction, she noted in a 2021 commentary marking 40 years since the first reported cases of acquired immunodeficiency syndrome.

In her laboratory, Dr. Leung is using new epigenetic markers to look at the pathogenesis of accelerated aging in the lung. By profiling bronchial epithelial brushings for DNA methylation and gene expression, they have found that “people living with both HIV and COPD have the fastest epigenetic age acceleration in their airway epithelium,” she said. The findings “suggest that the HIV lung is aging faster.”

They reported their findings in 2022, describing methylation disruptions along age-related pathways such as cellular senescence, longevity regulation, and insulin signaling.

Dr. Leung and her team have also studied the lung microbiome and found lower microbial diversity in the airway epithelium in patients with HIV than those without, especially in those with HIV and COPD. The National Institutes of Health–sponsored Lung HIV Microbiome Project found that changes in the lung microbiome are most pronounced in patients who haven’t yet initiated ART, but research in her lab suggests ongoing suppression of microbial diversity even after ART, she said.

Dr. Morris is particularly interested in the oral microbiome, having found through her research that changes in the oral microbiome in PWH were more related to impaired lung function than alterations in the lung and gut microbiome. “That may be in part because of the way we measure things,” she said. “But we also think that the oral microbiome probably seeds the lung [through micro-aspiration].” A study published in 2020 from the Pittsburgh site of the MACS described alterations in oral microbial communities in PWH with abnormal lung function.

Preliminary research suggests that improved dental cleaning and periodontal work in PWH and COPD may influence the severity of COPD, she noted.

“We don’t see as much of a signal with the gut microbiome [and HIV status or lung function], though there could still be ways in which gut microbiome influences the lung,” through systemic inflammation, the release of metabolites into the bloodstream, or microbial translocation, for instance, she said.

The potential role of translocation of members of the microbiome, in fact, is an area of active research for Dr. Morris. Members of the microbiome – viruses and fungi in addition to bacteria – “can get into the bloodstream from the mouth, from the lung, from the gut, to stimulate inflammation and worsen lung disease,” she said.
 

Key questions in an evolving research landscape

Dr. Kunisaki looks forward to research providing a more longitudinal look at lung function decline– a move beyond a dominance of cross-sectional studies – as well as research that is more comprehensive, with simultaneous collection of various functional measures (eg., DLCO with chest imaging and fractional excretion of nitric oxide (FENO – a standardized breath measure of Th2 airway inflammation).

The several-year-old NIH-supported MACS/WIHS (Women’s Interagency HIV Study) Combined Cohort study, in which Dr. Kunisaki and Dr. Morris participate, aims in part to identity biomarkers of increased risk for chronic lung disease and other chronic disorders and to develop strategies for more effective interventions and treatments.

Researchers will also share biospecimens, “which will allow more mechanistic work,” Dr. Kunisaki noted. (The combined cohort study includes participants from the earlier, separate MACS and WIHS studies.)

Questions about treatment strategies include the risks versus benefits of inhaled corticosteroids, which may increase an already elevated risk of respiratory infections like bacterial pneumonia in PWH, Dr. Kunisaki said.

[An aside: Inhaled corticosteroids also have well-described interactions with ART regimens that contain CYP3A4 inhibitors (e.g., ritonavir and cobicistat) that can lead to hypercortisolism. In patients who require both types of drugs, he said, beclomethasone has the least interactions and is the preferred inhaled corticosteroid.]

For Dr. Crothers, unanswered critical questions include – as she wrote in her 2021 commentary – the question of how guidelines for the management of COPD and asthma should be adapted for PWH. Is COPD in PWH more or less responsive to inhaled corticosteroids, for instance? And are antifibrotic treatments for interstitial lung disease and immunotherapies for asthma or lung cancer similarly effective, and are there any increased risks for harms in people with HIV?

There’s also the question of whether PWH should be screened for lung cancer earlier and with a lower smoking exposure than is advised under current guidelines for the general population, she said in the interview. “And should the approach to shared decision-making be modified for people with HIV?” she said. “We’re doing some work on these questions” right now.

None of the researchers interviewed reported any conflicts of interest relevant to the story. Dr. Kunisaki reported that he has no relevant disclosures, and said that his comments are his personal views and not official views of the U.S. Government, Department of Veterans Affairs, the Minneapolis VA, or the University of Minnesota.