HIV

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

The long-acting drug lenacapavir, a first-in-class capsid inhibitor, shows sustained viral suppression in a small cohort of heavily treatment-experienced patients with multidrug-resistant HIV at 26 weeks when combined with an optimized antiretroviral therapy. With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months.
 

“These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, [it] could help reduce pill burden,” first author Jean-Michel Molina, MD, PhD, professor of infectious diseases and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals, Paris, said in an interview.

Presenting the updated findings from the phase 2/3 CAPELLA trial at the virtual annual meeting of the International AIDS Society conference, Dr. Molina underscored the need for longer-term treatments.

“These patients with multidrug resistances are usually those who have not been fully adherent to their regimen,” he said. “Being able to provide the drug, given every 6 months subcutaneously, provides an ideal treatment for overcoming resistance and lack of adherence.”

The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir (927 mg) combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (<50 copies/mL).

In addition, the lenacapavir-treated patients had a clinically meaningful mean increase in CD4 counts of 81 cells/mcL over the 26 weeks.

The drug was well tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. The most common adverse events were injection-site reactions, which occurred in 56% of participants, with most being mild or moderate.

Importantly, four participants developed emergent resistances to lenacapavir. One was suppressed with a change in the background regimen and two others were suppressed without a change in regimen.

“We know that these mutations affect viral fitness,” Dr. Molina said in an interview. “We need more studies to assess the real impact of these mutations.”

Dr. Molina noted that a phase 2 study is already underway to evaluate how a pairing of lenacapavir with fellow investigational long-acting drug islatravir (Merck) could offset the risk of developing resistances.

Asked by an audience member whether a two-drug regimen with something like islatravir is likely to successfully prevent resistances, Dr. Molina responded that “it’s too early to know what’s going to happen with [combinations], but these first results are really encouraging when you see the very high rate of being fully suppressed after 26 weeks. The efficacy that we’ve seen after [a previous 2-week analysis] is long lasting.”
 

Lenacapavir targets multiple viral stages

Unlike other antiviral drugs that target just a single stage of viral replication, lenacapavir takes aim at multiple steps in the viral life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, Dr. Molina explained.

The CAPELLA trial included participants at research centers in North America, Europe, and Asia, with a median age of 52 years; 25% were female, 38% were Black, and their mean HIV-1 RNA (viral load) was 4.17 log copies/mL.

Overall, 72 patients were divided into two cohorts of 36 patients each, including a randomized and nonrandomized cohort. Dr. Molina primarily reported results from the randomized group.

In that group, patients received either a lead-in of oral lenacapavir (600 mg on day 1 and 2 and 300 mg on day 8) or placebo, in combination with patients’ current failing drug regimens in both groups.

At day 15, all participants were switched to the investigator-selected, optimized background treatment regimen, tailored according to patients’ drug-resistance profiles, and those in the lenacapavir group received the subcutaneous injection of lenacapavir; those in the placebo group were switched to the oral lead-in, followed by subcutaneous lenacapavir every 6 months.

Combined data that included six patients from the nonrandomized cohort showed that 79% of patients had a viral load of less than 50 copies/mL at week 26. The 81% viral suppression rate represented the randomized group (29 of 36).

International AIDS Society cochair Hendrik Streeck, MD, director of the Institute of Virology and Institute for HIV Research at the University Bonn (Germany), said a twice-a-year drug could possibly have profound benefits with a reduction in daily pill burden.

“What makes this an interesting drug is that it is long acting, so one can imagine it has the potential to treat individuals such as those who are not very adherent to the antiretroviral therapy, or who can’t easily access treatment, for example in resource-limited settings,” he said in an interview. “The option to treat patients for the next months in advance could be a very important next step.”
 

Further data from CALIBRATE

Additional data on lenacapavir from the phase 2 CALIBRATE study, presented in a separate session, further showed the drug, given orally or subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide, resulted in high rates of viral suppression among 94% of 157 treatment-naive patients after 28 weeks.

Commenting on the research, session moderator Alexandra Calmy, MD, PhD, of the HIV/AIDS unit and LIPO & Metabolism group, infectious diseases division, Geneva University Hospitals, noted the study offered “interesting data indeed” – with some caveats: “Why position a new drug class in naive patients [when] we already have good options, available for a large range of various populations?”

Dr. Calmy noted that, in general, lenacapavir “would certainly be an added value with an adapted 6-monthly companion drug.”

But she raised another key issue: “When will we have data on pregnancy that would allow lenacapavir to really be a game changer worldwide?”

The study was funded by Gilead Sciences. Dr. Molina reported receiving research funding from Gilead and being on advisory boards for Gilead, Merck, ViiV, and Janssen. Dr. Calmy and Dr. Streeck reported no relevant financial relationships.

The long-acting drug lenacapavir, a first-in-class capsid inhibitor, shows sustained viral suppression in a small cohort of heavily treatment-experienced patients with multidrug-resistant HIV at 26 weeks when combined with an optimized antiretroviral therapy. With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months.
 

“These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, [it] could help reduce pill burden,” first author Jean-Michel Molina, MD, PhD, professor of infectious diseases and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals, Paris, said in an interview.

Presenting the updated findings from the phase 2/3 CAPELLA trial at the virtual annual meeting of the International AIDS Society conference, Dr. Molina underscored the need for longer-term treatments.

“These patients with multidrug resistances are usually those who have not been fully adherent to their regimen,” he said. “Being able to provide the drug, given every 6 months subcutaneously, provides an ideal treatment for overcoming resistance and lack of adherence.”

The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir (927 mg) combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (<50 copies/mL).

In addition, the lenacapavir-treated patients had a clinically meaningful mean increase in CD4 counts of 81 cells/mcL over the 26 weeks.

The drug was well tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. The most common adverse events were injection-site reactions, which occurred in 56% of participants, with most being mild or moderate.

Importantly, four participants developed emergent resistances to lenacapavir. One was suppressed with a change in the background regimen and two others were suppressed without a change in regimen.

“We know that these mutations affect viral fitness,” Dr. Molina said in an interview. “We need more studies to assess the real impact of these mutations.”

Dr. Molina noted that a phase 2 study is already underway to evaluate how a pairing of lenacapavir with fellow investigational long-acting drug islatravir (Merck) could offset the risk of developing resistances.

Asked by an audience member whether a two-drug regimen with something like islatravir is likely to successfully prevent resistances, Dr. Molina responded that “it’s too early to know what’s going to happen with [combinations], but these first results are really encouraging when you see the very high rate of being fully suppressed after 26 weeks. The efficacy that we’ve seen after [a previous 2-week analysis] is long lasting.”
 

Lenacapavir targets multiple viral stages

Unlike other antiviral drugs that target just a single stage of viral replication, lenacapavir takes aim at multiple steps in the viral life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, Dr. Molina explained.

The CAPELLA trial included participants at research centers in North America, Europe, and Asia, with a median age of 52 years; 25% were female, 38% were Black, and their mean HIV-1 RNA (viral load) was 4.17 log copies/mL.

Overall, 72 patients were divided into two cohorts of 36 patients each, including a randomized and nonrandomized cohort. Dr. Molina primarily reported results from the randomized group.

In that group, patients received either a lead-in of oral lenacapavir (600 mg on day 1 and 2 and 300 mg on day 8) or placebo, in combination with patients’ current failing drug regimens in both groups.

At day 15, all participants were switched to the investigator-selected, optimized background treatment regimen, tailored according to patients’ drug-resistance profiles, and those in the lenacapavir group received the subcutaneous injection of lenacapavir; those in the placebo group were switched to the oral lead-in, followed by subcutaneous lenacapavir every 6 months.

Combined data that included six patients from the nonrandomized cohort showed that 79% of patients had a viral load of less than 50 copies/mL at week 26. The 81% viral suppression rate represented the randomized group (29 of 36).

International AIDS Society cochair Hendrik Streeck, MD, director of the Institute of Virology and Institute for HIV Research at the University Bonn (Germany), said a twice-a-year drug could possibly have profound benefits with a reduction in daily pill burden.

“What makes this an interesting drug is that it is long acting, so one can imagine it has the potential to treat individuals such as those who are not very adherent to the antiretroviral therapy, or who can’t easily access treatment, for example in resource-limited settings,” he said in an interview. “The option to treat patients for the next months in advance could be a very important next step.”
 

Further data from CALIBRATE

Additional data on lenacapavir from the phase 2 CALIBRATE study, presented in a separate session, further showed the drug, given orally or subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide, resulted in high rates of viral suppression among 94% of 157 treatment-naive patients after 28 weeks.

Commenting on the research, session moderator Alexandra Calmy, MD, PhD, of the HIV/AIDS unit and LIPO & Metabolism group, infectious diseases division, Geneva University Hospitals, noted the study offered “interesting data indeed” – with some caveats: “Why position a new drug class in naive patients [when] we already have good options, available for a large range of various populations?”

Dr. Calmy noted that, in general, lenacapavir “would certainly be an added value with an adapted 6-monthly companion drug.”

But she raised another key issue: “When will we have data on pregnancy that would allow lenacapavir to really be a game changer worldwide?”

The study was funded by Gilead Sciences. Dr. Molina reported receiving research funding from Gilead and being on advisory boards for Gilead, Merck, ViiV, and Janssen. Dr. Calmy and Dr. Streeck reported no relevant financial relationships.

The long-acting drug lenacapavir, a first-in-class capsid inhibitor, shows sustained viral suppression in a small cohort of heavily treatment-experienced patients with multidrug-resistant HIV at 26 weeks when combined with an optimized antiretroviral therapy. With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months.
 

“These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, [it] could help reduce pill burden,” first author Jean-Michel Molina, MD, PhD, professor of infectious diseases and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals, Paris, said in an interview.

Presenting the updated findings from the phase 2/3 CAPELLA trial at the virtual annual meeting of the International AIDS Society conference, Dr. Molina underscored the need for longer-term treatments.

“These patients with multidrug resistances are usually those who have not been fully adherent to their regimen,” he said. “Being able to provide the drug, given every 6 months subcutaneously, provides an ideal treatment for overcoming resistance and lack of adherence.”

The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir (927 mg) combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (<50 copies/mL).

In addition, the lenacapavir-treated patients had a clinically meaningful mean increase in CD4 counts of 81 cells/mcL over the 26 weeks.

The drug was well tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. The most common adverse events were injection-site reactions, which occurred in 56% of participants, with most being mild or moderate.

Importantly, four participants developed emergent resistances to lenacapavir. One was suppressed with a change in the background regimen and two others were suppressed without a change in regimen.

“We know that these mutations affect viral fitness,” Dr. Molina said in an interview. “We need more studies to assess the real impact of these mutations.”

Dr. Molina noted that a phase 2 study is already underway to evaluate how a pairing of lenacapavir with fellow investigational long-acting drug islatravir (Merck) could offset the risk of developing resistances.

Asked by an audience member whether a two-drug regimen with something like islatravir is likely to successfully prevent resistances, Dr. Molina responded that “it’s too early to know what’s going to happen with [combinations], but these first results are really encouraging when you see the very high rate of being fully suppressed after 26 weeks. The efficacy that we’ve seen after [a previous 2-week analysis] is long lasting.”
 

Lenacapavir targets multiple viral stages

Unlike other antiviral drugs that target just a single stage of viral replication, lenacapavir takes aim at multiple steps in the viral life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, Dr. Molina explained.

The CAPELLA trial included participants at research centers in North America, Europe, and Asia, with a median age of 52 years; 25% were female, 38% were Black, and their mean HIV-1 RNA (viral load) was 4.17 log copies/mL.

Overall, 72 patients were divided into two cohorts of 36 patients each, including a randomized and nonrandomized cohort. Dr. Molina primarily reported results from the randomized group.

In that group, patients received either a lead-in of oral lenacapavir (600 mg on day 1 and 2 and 300 mg on day 8) or placebo, in combination with patients’ current failing drug regimens in both groups.

At day 15, all participants were switched to the investigator-selected, optimized background treatment regimen, tailored according to patients’ drug-resistance profiles, and those in the lenacapavir group received the subcutaneous injection of lenacapavir; those in the placebo group were switched to the oral lead-in, followed by subcutaneous lenacapavir every 6 months.

Combined data that included six patients from the nonrandomized cohort showed that 79% of patients had a viral load of less than 50 copies/mL at week 26. The 81% viral suppression rate represented the randomized group (29 of 36).

International AIDS Society cochair Hendrik Streeck, MD, director of the Institute of Virology and Institute for HIV Research at the University Bonn (Germany), said a twice-a-year drug could possibly have profound benefits with a reduction in daily pill burden.

“What makes this an interesting drug is that it is long acting, so one can imagine it has the potential to treat individuals such as those who are not very adherent to the antiretroviral therapy, or who can’t easily access treatment, for example in resource-limited settings,” he said in an interview. “The option to treat patients for the next months in advance could be a very important next step.”
 

Further data from CALIBRATE

Additional data on lenacapavir from the phase 2 CALIBRATE study, presented in a separate session, further showed the drug, given orally or subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide, resulted in high rates of viral suppression among 94% of 157 treatment-naive patients after 28 weeks.

Commenting on the research, session moderator Alexandra Calmy, MD, PhD, of the HIV/AIDS unit and LIPO & Metabolism group, infectious diseases division, Geneva University Hospitals, noted the study offered “interesting data indeed” – with some caveats: “Why position a new drug class in naive patients [when] we already have good options, available for a large range of various populations?”

Dr. Calmy noted that, in general, lenacapavir “would certainly be an added value with an adapted 6-monthly companion drug.”

But she raised another key issue: “When will we have data on pregnancy that would allow lenacapavir to really be a game changer worldwide?”

The study was funded by Gilead Sciences. Dr. Molina reported receiving research funding from Gilead and being on advisory boards for Gilead, Merck, ViiV, and Janssen. Dr. Calmy and Dr. Streeck reported no relevant financial relationships.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Worldwide, nearly 8% of men who have sex with men (MSM) may have syphilis, a new systematic review and meta-analysis suggests. This estimate, generated from 275 studies across 77 countries, is 15 times greater than the most recent estimates of syphilis prevalence in men in a general population.

“That disparity is absolutely unacceptable,” Matthew Chico, PhD, associate professor at the London School of Hygiene and Tropical Medicine, and senior author of the review, said in an interview.

Although the World Health Organization (WHO) aims to reduce the global prevalence of syphilis by 90% by 2030, an ambitious goal set in 2016, recent research suggests syphilis numbers are moving in the opposite direction. Cases in the United States rose 74% between 2015 and 2019, and other nations, such as Australia, South Korea, and the United Kingdom, are seeing similar trends.

Syphilis prevalence is generally higher in MSM, largely in subpopulations of men who have multiple sexual partners, Kenneth Mayer, MD, said in an interview. Dr. Mayer is medical research director at the Fenway Institute, Boston, and was not involved with the study.

Health literacy, lack of access to care, and medical mistrust can all be challenges to screening, identifying, and treating the infection in this population.

Reducing syphilis cases will require focusing interventions on higher-risk groups such as MSM, said Dr. Chico; however, there was “a real dearth in knowledge about the most likely prevalence of syphilis among MSM on a global level,” he said.

To help fill in the gaps, Dr. Chico and his research team collected studies that included syphilis prevalence data for MSM published between Jan. 1, 2000, and Feb. 1, 2020. Researchers excluded studies that included only MSM living with HIV, injection drug users, patients who routinely visit sexually transmitted infection (STI) clinics, and people seeking care only for STIs or other genital symptoms, because these studies would have skewed global syphilis prevalence estimates higher.

Their review, published July 8 in The Lancet Global Health, found that the pooled global prevalence of syphilis from 2000-2020 in MSM was 7.5%. It ranged from 1.9% in Australia and New Zealand to 10.6% in Latin America and the Caribbean. In comparison, the WHO estimates that globally, 0.5% of men in a general population have syphilis, a 15-fold difference.

This elevated estimate is not surprising, and the review provides a more international view of syphilis. Earlier attempts to estimate the prevalence of syphilis among MSM were generally conducted in higher-income countries such as the United States, Dr. Mayer said. “It’s important that clinicians recognize that this is a global health issue, so they can do the appropriate screening.”

The review found that regions in which the prevalence of HIV was above 5% had higher rates of syphilis (8.7%) compared to regions in which the prevalence of HIV was below 5% (6.6%). Pooled syphilis prevalence estimates were also higher for lower-middle-income and upper-middle-income countries (8.7% and 8.6%, respectively).

Global syphilis prevalence dipped from 8.9% in studies from 2000 to 2009 to 6.6% in studies from 2010 to 2020. In Europe, Northern America, Latin America, the Caribbean, and Oceania (excluding Australia and New Zealand), syphilis prevalence estimates for 2015-2020 were higher compared with 2010-2014.

The authors acknowledged that there were some limitations to the study, particularly that regions of Eastern and Southeastern Asia contributed more than half (54.5%) of the global data points used in the study and accounted for more than 82% of the study’s participants. This highlights the lack of data from other regions around the world, Dr. Chico said.

Dr. Chico said these findings “serve as a clarion call to action” to focus interventions on groups at higher risk for syphilis, such as MSM, in the effort to drastically reduce syphilis cases around the world. Dr. Mayer agrees. “[Syphilis] is a readily diagnosable and treatable infection,” he said. “It definitely is something that we should be able to get a handle on, but that requires paying attention to the different subgroups who have particularly high rates of the infection.”

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

Worldwide, nearly 8% of men who have sex with men (MSM) may have syphilis, a new systematic review and meta-analysis suggests. This estimate, generated from 275 studies across 77 countries, is 15 times greater than the most recent estimates of syphilis prevalence in men in a general population.

“That disparity is absolutely unacceptable,” Matthew Chico, PhD, associate professor at the London School of Hygiene and Tropical Medicine, and senior author of the review, said in an interview.

Although the World Health Organization (WHO) aims to reduce the global prevalence of syphilis by 90% by 2030, an ambitious goal set in 2016, recent research suggests syphilis numbers are moving in the opposite direction. Cases in the United States rose 74% between 2015 and 2019, and other nations, such as Australia, South Korea, and the United Kingdom, are seeing similar trends.

Syphilis prevalence is generally higher in MSM, largely in subpopulations of men who have multiple sexual partners, Kenneth Mayer, MD, said in an interview. Dr. Mayer is medical research director at the Fenway Institute, Boston, and was not involved with the study.

Health literacy, lack of access to care, and medical mistrust can all be challenges to screening, identifying, and treating the infection in this population.

Reducing syphilis cases will require focusing interventions on higher-risk groups such as MSM, said Dr. Chico; however, there was “a real dearth in knowledge about the most likely prevalence of syphilis among MSM on a global level,” he said.

To help fill in the gaps, Dr. Chico and his research team collected studies that included syphilis prevalence data for MSM published between Jan. 1, 2000, and Feb. 1, 2020. Researchers excluded studies that included only MSM living with HIV, injection drug users, patients who routinely visit sexually transmitted infection (STI) clinics, and people seeking care only for STIs or other genital symptoms, because these studies would have skewed global syphilis prevalence estimates higher.

Their review, published July 8 in The Lancet Global Health, found that the pooled global prevalence of syphilis from 2000-2020 in MSM was 7.5%. It ranged from 1.9% in Australia and New Zealand to 10.6% in Latin America and the Caribbean. In comparison, the WHO estimates that globally, 0.5% of men in a general population have syphilis, a 15-fold difference.

This elevated estimate is not surprising, and the review provides a more international view of syphilis. Earlier attempts to estimate the prevalence of syphilis among MSM were generally conducted in higher-income countries such as the United States, Dr. Mayer said. “It’s important that clinicians recognize that this is a global health issue, so they can do the appropriate screening.”

The review found that regions in which the prevalence of HIV was above 5% had higher rates of syphilis (8.7%) compared to regions in which the prevalence of HIV was below 5% (6.6%). Pooled syphilis prevalence estimates were also higher for lower-middle-income and upper-middle-income countries (8.7% and 8.6%, respectively).

Global syphilis prevalence dipped from 8.9% in studies from 2000 to 2009 to 6.6% in studies from 2010 to 2020. In Europe, Northern America, Latin America, the Caribbean, and Oceania (excluding Australia and New Zealand), syphilis prevalence estimates for 2015-2020 were higher compared with 2010-2014.

The authors acknowledged that there were some limitations to the study, particularly that regions of Eastern and Southeastern Asia contributed more than half (54.5%) of the global data points used in the study and accounted for more than 82% of the study’s participants. This highlights the lack of data from other regions around the world, Dr. Chico said.

Dr. Chico said these findings “serve as a clarion call to action” to focus interventions on groups at higher risk for syphilis, such as MSM, in the effort to drastically reduce syphilis cases around the world. Dr. Mayer agrees. “[Syphilis] is a readily diagnosable and treatable infection,” he said. “It definitely is something that we should be able to get a handle on, but that requires paying attention to the different subgroups who have particularly high rates of the infection.”

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

Worldwide, nearly 8% of men who have sex with men (MSM) may have syphilis, a new systematic review and meta-analysis suggests. This estimate, generated from 275 studies across 77 countries, is 15 times greater than the most recent estimates of syphilis prevalence in men in a general population.

“That disparity is absolutely unacceptable,” Matthew Chico, PhD, associate professor at the London School of Hygiene and Tropical Medicine, and senior author of the review, said in an interview.

Although the World Health Organization (WHO) aims to reduce the global prevalence of syphilis by 90% by 2030, an ambitious goal set in 2016, recent research suggests syphilis numbers are moving in the opposite direction. Cases in the United States rose 74% between 2015 and 2019, and other nations, such as Australia, South Korea, and the United Kingdom, are seeing similar trends.

Syphilis prevalence is generally higher in MSM, largely in subpopulations of men who have multiple sexual partners, Kenneth Mayer, MD, said in an interview. Dr. Mayer is medical research director at the Fenway Institute, Boston, and was not involved with the study.

Health literacy, lack of access to care, and medical mistrust can all be challenges to screening, identifying, and treating the infection in this population.

Reducing syphilis cases will require focusing interventions on higher-risk groups such as MSM, said Dr. Chico; however, there was “a real dearth in knowledge about the most likely prevalence of syphilis among MSM on a global level,” he said.

To help fill in the gaps, Dr. Chico and his research team collected studies that included syphilis prevalence data for MSM published between Jan. 1, 2000, and Feb. 1, 2020. Researchers excluded studies that included only MSM living with HIV, injection drug users, patients who routinely visit sexually transmitted infection (STI) clinics, and people seeking care only for STIs or other genital symptoms, because these studies would have skewed global syphilis prevalence estimates higher.

Their review, published July 8 in The Lancet Global Health, found that the pooled global prevalence of syphilis from 2000-2020 in MSM was 7.5%. It ranged from 1.9% in Australia and New Zealand to 10.6% in Latin America and the Caribbean. In comparison, the WHO estimates that globally, 0.5% of men in a general population have syphilis, a 15-fold difference.

This elevated estimate is not surprising, and the review provides a more international view of syphilis. Earlier attempts to estimate the prevalence of syphilis among MSM were generally conducted in higher-income countries such as the United States, Dr. Mayer said. “It’s important that clinicians recognize that this is a global health issue, so they can do the appropriate screening.”

The review found that regions in which the prevalence of HIV was above 5% had higher rates of syphilis (8.7%) compared to regions in which the prevalence of HIV was below 5% (6.6%). Pooled syphilis prevalence estimates were also higher for lower-middle-income and upper-middle-income countries (8.7% and 8.6%, respectively).

Global syphilis prevalence dipped from 8.9% in studies from 2000 to 2009 to 6.6% in studies from 2010 to 2020. In Europe, Northern America, Latin America, the Caribbean, and Oceania (excluding Australia and New Zealand), syphilis prevalence estimates for 2015-2020 were higher compared with 2010-2014.

The authors acknowledged that there were some limitations to the study, particularly that regions of Eastern and Southeastern Asia contributed more than half (54.5%) of the global data points used in the study and accounted for more than 82% of the study’s participants. This highlights the lack of data from other regions around the world, Dr. Chico said.

Dr. Chico said these findings “serve as a clarion call to action” to focus interventions on groups at higher risk for syphilis, such as MSM, in the effort to drastically reduce syphilis cases around the world. Dr. Mayer agrees. “[Syphilis] is a readily diagnosable and treatable infection,” he said. “It definitely is something that we should be able to get a handle on, but that requires paying attention to the different subgroups who have particularly high rates of the infection.”

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

The COVID-19 pandemic has overshadowed innovations in HIV care and prevention, says Tonia Poteat, PhD, MPH, PA-C, a primary HIV care and HIV pre-exposure prophylaxis (PrEP) clinician and associate professor of social medicine at the University of North Carolina at Chapel Hill. Therefore, even though the U.S. Food and Drug Administration approved monthly injections of cabotegravir/rilpivirine (Cabenuva) in January, none of her patients are taking it.

“We moved our clinic three times during the pandemic,” Dr. Poteat said. “I’m really interested in how on earth we’re going to integrate injectable products into our workflow. We don’t have systems set up yet, so we’re in the process of figuring out what the structure is going to be like. We have people who are interested on a wait list.”

Indeed, in an HIV world still reeling from the dual impact of HIV and COVID-19, the International AIDS Society Conference on HIV Science (IAS 2021) will bring a more coherent narrative on the future of HIV treatment and prevention. That narrative involves long-acting treatment and setting up the systems to make it available to everyone. And IAS offers data showing exactly how much people living with HIV risk poor COVID-19 outcomes.

The conference will be online for the second year in a row and, unlike in 2020, the focus will be much more on HIV treatment and prevention than on that other big infectious disease making news these days.

There will be new data on long-acting forms of prevention, such as the intravaginal ring and monthly PrEP pills. There will be new data on PrEP on demand (2-1-1 PrEP) and the results of a large trial looking at breakthrough HIV infections among those taking daily oral PrEP.

On the treatment side, trial results will be announced on cabotegravir/rilpivirine and islatravir long-acting treatment, as well as additional data on the effectiveness of two-drug antiretrovial therapy dolutegravir/lamivudine (Dovato) and bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), specifically in Black participants.

On the cure front, intriguing animal studies and ex vivo studies look into the use of cancer immunotherapies for an HIV functional cure, as well as the use of CAR-T to stop HIV replication in the absence of daily medication.

Dr. Poteat is not alone in being interested specifically in the PrEP and long-acting studies. Jonathan Baker, a PA in private practice in New York City, also wants to see the data on the ring and other expanded PrEP options.

But “a prevention method can only work when people are able to use it,” he said. “So [the session] ‘Reducing Barriers to PrEP’ is really relevant as we see inequitable intake failing the populations who need PrEP most.”

This is a concern Dr. Poteat has too. That’s why she’s glad to see there will be sessions on systemic inequities, particularly around what it will take to address those inequities in the U.S. by 2030 in line with “Ending the HIV Epidemic: A Plan for America.” She’s looking forward to sessions on novel service-delivery models with low thresholds of entry for people experiencing homelessness or people who inject drugs; on access to affordable medications; on trans-led care for transgender women in the global South; and on the comorbidities of aging that are keeping her patients sick these days. 

To that end, there are sessions on common comorbidities with HIV, such as reinfection with hepatitis C, sexually transmitted infections, heart disease, and weight gain as a result of newer drug options, as well as drug-drug interactions between HIV medications and those used in gender-affirming care for transgender adults.

“I can count on one hand the number of people for whom the issue is finding the right antiretroviral,” she said. “That’s rarely the issue. The issue is often how do we manage their other comorbid conditions, and what about drug-drug interactions with those conditions? HIV is not the only condition many of them have.”

Mr. Baker reports that his clinic receives funding from Merck, Innovio, and Antiva. Dr. Poteat is a consultant for ViiV Healthcare and serves on a study advisory board for Merck.

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

The COVID-19 pandemic has overshadowed innovations in HIV care and prevention, says Tonia Poteat, PhD, MPH, PA-C, a primary HIV care and HIV pre-exposure prophylaxis (PrEP) clinician and associate professor of social medicine at the University of North Carolina at Chapel Hill. Therefore, even though the U.S. Food and Drug Administration approved monthly injections of cabotegravir/rilpivirine (Cabenuva) in January, none of her patients are taking it.

“We moved our clinic three times during the pandemic,” Dr. Poteat said. “I’m really interested in how on earth we’re going to integrate injectable products into our workflow. We don’t have systems set up yet, so we’re in the process of figuring out what the structure is going to be like. We have people who are interested on a wait list.”

Indeed, in an HIV world still reeling from the dual impact of HIV and COVID-19, the International AIDS Society Conference on HIV Science (IAS 2021) will bring a more coherent narrative on the future of HIV treatment and prevention. That narrative involves long-acting treatment and setting up the systems to make it available to everyone. And IAS offers data showing exactly how much people living with HIV risk poor COVID-19 outcomes.

The conference will be online for the second year in a row and, unlike in 2020, the focus will be much more on HIV treatment and prevention than on that other big infectious disease making news these days.

There will be new data on long-acting forms of prevention, such as the intravaginal ring and monthly PrEP pills. There will be new data on PrEP on demand (2-1-1 PrEP) and the results of a large trial looking at breakthrough HIV infections among those taking daily oral PrEP.

On the treatment side, trial results will be announced on cabotegravir/rilpivirine and islatravir long-acting treatment, as well as additional data on the effectiveness of two-drug antiretrovial therapy dolutegravir/lamivudine (Dovato) and bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), specifically in Black participants.

On the cure front, intriguing animal studies and ex vivo studies look into the use of cancer immunotherapies for an HIV functional cure, as well as the use of CAR-T to stop HIV replication in the absence of daily medication.

Dr. Poteat is not alone in being interested specifically in the PrEP and long-acting studies. Jonathan Baker, a PA in private practice in New York City, also wants to see the data on the ring and other expanded PrEP options.

But “a prevention method can only work when people are able to use it,” he said. “So [the session] ‘Reducing Barriers to PrEP’ is really relevant as we see inequitable intake failing the populations who need PrEP most.”

This is a concern Dr. Poteat has too. That’s why she’s glad to see there will be sessions on systemic inequities, particularly around what it will take to address those inequities in the U.S. by 2030 in line with “Ending the HIV Epidemic: A Plan for America.” She’s looking forward to sessions on novel service-delivery models with low thresholds of entry for people experiencing homelessness or people who inject drugs; on access to affordable medications; on trans-led care for transgender women in the global South; and on the comorbidities of aging that are keeping her patients sick these days. 

To that end, there are sessions on common comorbidities with HIV, such as reinfection with hepatitis C, sexually transmitted infections, heart disease, and weight gain as a result of newer drug options, as well as drug-drug interactions between HIV medications and those used in gender-affirming care for transgender adults.

“I can count on one hand the number of people for whom the issue is finding the right antiretroviral,” she said. “That’s rarely the issue. The issue is often how do we manage their other comorbid conditions, and what about drug-drug interactions with those conditions? HIV is not the only condition many of them have.”

Mr. Baker reports that his clinic receives funding from Merck, Innovio, and Antiva. Dr. Poteat is a consultant for ViiV Healthcare and serves on a study advisory board for Merck.

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

The COVID-19 pandemic has overshadowed innovations in HIV care and prevention, says Tonia Poteat, PhD, MPH, PA-C, a primary HIV care and HIV pre-exposure prophylaxis (PrEP) clinician and associate professor of social medicine at the University of North Carolina at Chapel Hill. Therefore, even though the U.S. Food and Drug Administration approved monthly injections of cabotegravir/rilpivirine (Cabenuva) in January, none of her patients are taking it.

“We moved our clinic three times during the pandemic,” Dr. Poteat said. “I’m really interested in how on earth we’re going to integrate injectable products into our workflow. We don’t have systems set up yet, so we’re in the process of figuring out what the structure is going to be like. We have people who are interested on a wait list.”

Indeed, in an HIV world still reeling from the dual impact of HIV and COVID-19, the International AIDS Society Conference on HIV Science (IAS 2021) will bring a more coherent narrative on the future of HIV treatment and prevention. That narrative involves long-acting treatment and setting up the systems to make it available to everyone. And IAS offers data showing exactly how much people living with HIV risk poor COVID-19 outcomes.

The conference will be online for the second year in a row and, unlike in 2020, the focus will be much more on HIV treatment and prevention than on that other big infectious disease making news these days.

There will be new data on long-acting forms of prevention, such as the intravaginal ring and monthly PrEP pills. There will be new data on PrEP on demand (2-1-1 PrEP) and the results of a large trial looking at breakthrough HIV infections among those taking daily oral PrEP.

On the treatment side, trial results will be announced on cabotegravir/rilpivirine and islatravir long-acting treatment, as well as additional data on the effectiveness of two-drug antiretrovial therapy dolutegravir/lamivudine (Dovato) and bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), specifically in Black participants.

On the cure front, intriguing animal studies and ex vivo studies look into the use of cancer immunotherapies for an HIV functional cure, as well as the use of CAR-T to stop HIV replication in the absence of daily medication.

Dr. Poteat is not alone in being interested specifically in the PrEP and long-acting studies. Jonathan Baker, a PA in private practice in New York City, also wants to see the data on the ring and other expanded PrEP options.

But “a prevention method can only work when people are able to use it,” he said. “So [the session] ‘Reducing Barriers to PrEP’ is really relevant as we see inequitable intake failing the populations who need PrEP most.”

This is a concern Dr. Poteat has too. That’s why she’s glad to see there will be sessions on systemic inequities, particularly around what it will take to address those inequities in the U.S. by 2030 in line with “Ending the HIV Epidemic: A Plan for America.” She’s looking forward to sessions on novel service-delivery models with low thresholds of entry for people experiencing homelessness or people who inject drugs; on access to affordable medications; on trans-led care for transgender women in the global South; and on the comorbidities of aging that are keeping her patients sick these days. 

To that end, there are sessions on common comorbidities with HIV, such as reinfection with hepatitis C, sexually transmitted infections, heart disease, and weight gain as a result of newer drug options, as well as drug-drug interactions between HIV medications and those used in gender-affirming care for transgender adults.

“I can count on one hand the number of people for whom the issue is finding the right antiretroviral,” she said. “That’s rarely the issue. The issue is often how do we manage their other comorbid conditions, and what about drug-drug interactions with those conditions? HIV is not the only condition many of them have.”

Mr. Baker reports that his clinic receives funding from Merck, Innovio, and Antiva. Dr. Poteat is a consultant for ViiV Healthcare and serves on a study advisory board for Merck.

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

For many people, being told that they are HIV positive is no longer a death sentence. But for Robert Suttle, a Black gay man and social justice educator, it is a life sentence.

Unexpectedly caught up in the HIV criminalization web at the age of 30, Mr. Suttle spent 6 months in a Louisiana state prison for a consensual sexual relationship with an adult partner. The crime? Not disclosing his HIV-positive status, a charge that Mr. Suttle says is untrue.

“I did disclose my status to my partner; however, I can’t really answer how they might have received it,” he said.

Today, at the age of 42, Mr. Suttle still carries the indelible stain of a conviction and of being a registered sex offender. “After their diagnosis, criminal charge, and/or conviction, many people think they’re done – either ‘I’ve gotten out of prison’ or ‘I’m still on probation’ – whatever the case may be,” he explained. “But we’re still living out these collateral consequences, be it with housing, moving to another state, or finding a job.”

The same is true for HIV-positive people who are charged and tried but manage to dodge prison for one reason or another. Monique Howell, a straight, 40-year-old former army soldier and single mother of five children, said that she was afraid to disclose her HIV status to a sexual partner but did advise him to wear a condom.* She points to her DD14 discharge papers (i.e., forms that verify that someone served in the military) that were issued when her military duty was rescinded following the dismissal of her court case.

“I was going to reenlist, but I got in trouble,” she said. She explained that although a DD14 separation helps to ensure that she can receive benefits and care, the papers were issued with a caveat stating “serious offense,” an indelible stain that, like Mr. Suttle’s, will follow her for the rest of her life.
 

Laws criminalize myths and misconceptions

HIV criminalization laws subject persons whose behaviors may expose others to HIV to felony or misdemeanor charges. Depending on the state, they can carry prison terms ranging from less than 10 years to life, according to the Centers for Disease Control and Prevention.

Originally enacted at the height of the AIDS epidemic in 1986, when fear was rampant and hundreds were dying, the laws were intended to reduce HIV transmission. But they’ve had unintended consequences: Amplifying stigmatization and discrimination and perpetuating HIV myths and misconceptions, including how HIV is transmitted.

Decades of scientific advances challenge the most basic reasoning behind laws (for example, that transmission is possible via biting or spitting or through a single sexual act, which studies have shown poses a risk as low as 0%-1.4%). In addition, few laws reflect one of the most important HIV research findings of the past decade: undetectable equals untransmittable, meaning that the virus cannot be sexually transmitted by people who are taking antiretroviral therapy and whose viral loads are undetectable.

In most of these cases, individuals who are positive for HIV are charged and punished for unintentional exposure, not deliberate intent to harm. Moreover, for the charge to stick, sexual partners don’t need to have acquired the virus or prove the transmission source if they do become HIV positive.

Ms. Howell noted that it was the Army that brought the charges against her, not her sexual partner at that time (who, incidentally, tested negative). He even testified on her behalf at the trial. “I’ll never forget it,” she said. “He said, ‘I don’t want anything to happen to Monique; even if you put her behind bars, she’s still HIV-positive and she’s still got those children. She told me to get a condom, and I chose not to.’ ”
 

Criminal vs. clinical fallout

In 2018, 20 scientists across the world issued a consensus statement underscoring the fact that HIV criminalization laws are based on fallacies and faulty science. The statement (which remains one of the most accessed in the Journal of the International AIDS Society) also points out that 33 countries (including the United States) use general criminal statutes such as attempted murder or reckless endangerment to lengthen sentences when people with HIV commit crimes.

When the laws were created, “many were the equivalent [to general criminal laws], because HIV was seen as a death sentence,” explained Chris Beyrer MD, MPH, professor of public health and human rights at Johns Hopkins Bloomberg School of Public Health, Baltimore. “So, failure to disclose your status, to wear a condom was seen as risking someone else’s life, which is no longer the case,” he added.

In fact, “from the perspective of the kinds of impact that these laws have had on transmission, or risk, or behavior, what you find is that they really have no public health benefit and they have real public harms,” said Dr. Beyrer.

Claire Farel, MD, assistant professor and medical director of the UNC Infectious Diseases Clinic at the University of North Carolina at Chapel Hill, concurs. “Because of the criminalization undercurrent, there are people who don’t get tested, meaning that they are at risk for worse health outcomes, such as cancer, vascular disease, and of course HIV-related poor outcomes, including progression to AIDS.”

Farel also points to the residual stigma associated with HIV. “Much of this is inextricable from that surrounding homophobia, especially among young men of color who have sex with men. It opens up a larger conversation that a lot of people don’t want to engage in,” she said.
 

Laws broaden existing disparities even further

The CDC released a study June 4 showing substantial declines in the overall incidence of HIV in the United States, with an important caveat: There’s been a worsening disparity in cases. Access to care and engagement with care remain poor among certain populations. For example, Black individuals accounted for 41% of new HIV infections in 2019, but they represent only 12% of the U.S. population; Hispanic/Latinx persons accounted for 29% of new infections, although they represent only 17% of the entire population.

The same is true for HIV criminalization: In 2020, more than 50% of defendants were people of color, according to U.S. case data collated by the HIV Justice Network.

Still, the momentum to change these antiquated laws is gaining speed. In May, the Illinois State Senate passed a bill repealing HIV criminalization, and this past March, Virginia’s Governor Ralph Northam signed a bill lowering HIV-related criminalization charges from a felony to a misdemeanor and changing the wording of its law to include both intent and transmission.** California, Colorado, Iowa, Michigan, Nevada, and North Carolina have also modernized or repealed their laws.
 

Ending the U.S. HIV epidemic: Patients first

Without true HIV criminalization reform, efforts to change the public and clinical mindset regarding HIV from its being a highly stigmatized disease to a preventable, treatable infection are likely to fall short. Dr. Beyrer emphasized that the onus lies with the scientific and activist communities working together. “I don’t know how you can end the epidemic if you are still stigmatizing the people who are actually acquiring these infections,” he said.

There are steps that patients can take while these forces push for change.

“As people first process their diagnosis, they need to learn as much about HIV and the science behind it as possible,” advised Mr. Suttle. He said that to protect oneself, it’s essential to learn about HIV criminalization and the laws in one’s state.

“Find someone you can trust, starting with your medical provider if possible, and if you have a significant other, bring that person to your appointments so they can see that you are in care and doing all that you can do to lower viral loads and protect others,” he added.

Ms. Howell said that although people should be in treatment and care, attitudes also need to change on the clinician side. “We’re just given these meds, told to take them, and are sent on our merry ways, but they don’t tell us how to live our lives properly; nobody grabs us and says, hey, these are the laws and you need to know this or that.”

When a person who is HIV positive does get caught up in the system, if possible, that person should consult an attorney who understands these laws. Mr. Suttle suggested reaching out to organizations in the movement to end HIV criminalization (e.g., the Sero Project, the Center for HIV Law and Policy, or the Positive Women’s Network) for further support, help with cases (including providing experts to testify), social services, and other resources. Mr. Suttle also encourages people who need help and direction to reach out to him directly at [email protected].

Forty years ago, the CDC published its first report of an illness in five healthy gay men living in Los Angeles. The first cases in women were reported shortly thereafter. Over the years, there have been many scientific advances in prevention and treatment. But as Dr. Beyrer aptly noted in an editorial published January 2021 in The Lancet HIV, “time has not lessened the sting of the early decades of AIDS.”

“We should not have to be afraid of who we are because we are HIV positive,” said Ms. Howell.

Dr. Farel, Mr. Suttle, and Ms. Howell report no relevant financial relationships. Dr. Beyrer has a consulting agreement with Merck.
 

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

*Correction, 6/14/2021: An earlier version of this story misstated Ms. Howell's age. She is 40.

**Correction, 6/14/2021: An earlier version of this story misspelled Gov. Northam's name.

For many people, being told that they are HIV positive is no longer a death sentence. But for Robert Suttle, a Black gay man and social justice educator, it is a life sentence.

Unexpectedly caught up in the HIV criminalization web at the age of 30, Mr. Suttle spent 6 months in a Louisiana state prison for a consensual sexual relationship with an adult partner. The crime? Not disclosing his HIV-positive status, a charge that Mr. Suttle says is untrue.

“I did disclose my status to my partner; however, I can’t really answer how they might have received it,” he said.

Today, at the age of 42, Mr. Suttle still carries the indelible stain of a conviction and of being a registered sex offender. “After their diagnosis, criminal charge, and/or conviction, many people think they’re done – either ‘I’ve gotten out of prison’ or ‘I’m still on probation’ – whatever the case may be,” he explained. “But we’re still living out these collateral consequences, be it with housing, moving to another state, or finding a job.”

The same is true for HIV-positive people who are charged and tried but manage to dodge prison for one reason or another. Monique Howell, a straight, 40-year-old former army soldier and single mother of five children, said that she was afraid to disclose her HIV status to a sexual partner but did advise him to wear a condom.* She points to her DD14 discharge papers (i.e., forms that verify that someone served in the military) that were issued when her military duty was rescinded following the dismissal of her court case.

“I was going to reenlist, but I got in trouble,” she said. She explained that although a DD14 separation helps to ensure that she can receive benefits and care, the papers were issued with a caveat stating “serious offense,” an indelible stain that, like Mr. Suttle’s, will follow her for the rest of her life.
 

Laws criminalize myths and misconceptions

HIV criminalization laws subject persons whose behaviors may expose others to HIV to felony or misdemeanor charges. Depending on the state, they can carry prison terms ranging from less than 10 years to life, according to the Centers for Disease Control and Prevention.

Originally enacted at the height of the AIDS epidemic in 1986, when fear was rampant and hundreds were dying, the laws were intended to reduce HIV transmission. But they’ve had unintended consequences: Amplifying stigmatization and discrimination and perpetuating HIV myths and misconceptions, including how HIV is transmitted.

Decades of scientific advances challenge the most basic reasoning behind laws (for example, that transmission is possible via biting or spitting or through a single sexual act, which studies have shown poses a risk as low as 0%-1.4%). In addition, few laws reflect one of the most important HIV research findings of the past decade: undetectable equals untransmittable, meaning that the virus cannot be sexually transmitted by people who are taking antiretroviral therapy and whose viral loads are undetectable.

In most of these cases, individuals who are positive for HIV are charged and punished for unintentional exposure, not deliberate intent to harm. Moreover, for the charge to stick, sexual partners don’t need to have acquired the virus or prove the transmission source if they do become HIV positive.

Ms. Howell noted that it was the Army that brought the charges against her, not her sexual partner at that time (who, incidentally, tested negative). He even testified on her behalf at the trial. “I’ll never forget it,” she said. “He said, ‘I don’t want anything to happen to Monique; even if you put her behind bars, she’s still HIV-positive and she’s still got those children. She told me to get a condom, and I chose not to.’ ”
 

Criminal vs. clinical fallout

In 2018, 20 scientists across the world issued a consensus statement underscoring the fact that HIV criminalization laws are based on fallacies and faulty science. The statement (which remains one of the most accessed in the Journal of the International AIDS Society) also points out that 33 countries (including the United States) use general criminal statutes such as attempted murder or reckless endangerment to lengthen sentences when people with HIV commit crimes.

When the laws were created, “many were the equivalent [to general criminal laws], because HIV was seen as a death sentence,” explained Chris Beyrer MD, MPH, professor of public health and human rights at Johns Hopkins Bloomberg School of Public Health, Baltimore. “So, failure to disclose your status, to wear a condom was seen as risking someone else’s life, which is no longer the case,” he added.

In fact, “from the perspective of the kinds of impact that these laws have had on transmission, or risk, or behavior, what you find is that they really have no public health benefit and they have real public harms,” said Dr. Beyrer.

Claire Farel, MD, assistant professor and medical director of the UNC Infectious Diseases Clinic at the University of North Carolina at Chapel Hill, concurs. “Because of the criminalization undercurrent, there are people who don’t get tested, meaning that they are at risk for worse health outcomes, such as cancer, vascular disease, and of course HIV-related poor outcomes, including progression to AIDS.”

Farel also points to the residual stigma associated with HIV. “Much of this is inextricable from that surrounding homophobia, especially among young men of color who have sex with men. It opens up a larger conversation that a lot of people don’t want to engage in,” she said.
 

Laws broaden existing disparities even further

The CDC released a study June 4 showing substantial declines in the overall incidence of HIV in the United States, with an important caveat: There’s been a worsening disparity in cases. Access to care and engagement with care remain poor among certain populations. For example, Black individuals accounted for 41% of new HIV infections in 2019, but they represent only 12% of the U.S. population; Hispanic/Latinx persons accounted for 29% of new infections, although they represent only 17% of the entire population.

The same is true for HIV criminalization: In 2020, more than 50% of defendants were people of color, according to U.S. case data collated by the HIV Justice Network.

Still, the momentum to change these antiquated laws is gaining speed. In May, the Illinois State Senate passed a bill repealing HIV criminalization, and this past March, Virginia’s Governor Ralph Northam signed a bill lowering HIV-related criminalization charges from a felony to a misdemeanor and changing the wording of its law to include both intent and transmission.** California, Colorado, Iowa, Michigan, Nevada, and North Carolina have also modernized or repealed their laws.
 

Ending the U.S. HIV epidemic: Patients first

Without true HIV criminalization reform, efforts to change the public and clinical mindset regarding HIV from its being a highly stigmatized disease to a preventable, treatable infection are likely to fall short. Dr. Beyrer emphasized that the onus lies with the scientific and activist communities working together. “I don’t know how you can end the epidemic if you are still stigmatizing the people who are actually acquiring these infections,” he said.

There are steps that patients can take while these forces push for change.

“As people first process their diagnosis, they need to learn as much about HIV and the science behind it as possible,” advised Mr. Suttle. He said that to protect oneself, it’s essential to learn about HIV criminalization and the laws in one’s state.

“Find someone you can trust, starting with your medical provider if possible, and if you have a significant other, bring that person to your appointments so they can see that you are in care and doing all that you can do to lower viral loads and protect others,” he added.

Ms. Howell said that although people should be in treatment and care, attitudes also need to change on the clinician side. “We’re just given these meds, told to take them, and are sent on our merry ways, but they don’t tell us how to live our lives properly; nobody grabs us and says, hey, these are the laws and you need to know this or that.”

When a person who is HIV positive does get caught up in the system, if possible, that person should consult an attorney who understands these laws. Mr. Suttle suggested reaching out to organizations in the movement to end HIV criminalization (e.g., the Sero Project, the Center for HIV Law and Policy, or the Positive Women’s Network) for further support, help with cases (including providing experts to testify), social services, and other resources. Mr. Suttle also encourages people who need help and direction to reach out to him directly at [email protected].

Forty years ago, the CDC published its first report of an illness in five healthy gay men living in Los Angeles. The first cases in women were reported shortly thereafter. Over the years, there have been many scientific advances in prevention and treatment. But as Dr. Beyrer aptly noted in an editorial published January 2021 in The Lancet HIV, “time has not lessened the sting of the early decades of AIDS.”

“We should not have to be afraid of who we are because we are HIV positive,” said Ms. Howell.

Dr. Farel, Mr. Suttle, and Ms. Howell report no relevant financial relationships. Dr. Beyrer has a consulting agreement with Merck.
 

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

*Correction, 6/14/2021: An earlier version of this story misstated Ms. Howell's age. She is 40.

**Correction, 6/14/2021: An earlier version of this story misspelled Gov. Northam's name.

For many people, being told that they are HIV positive is no longer a death sentence. But for Robert Suttle, a Black gay man and social justice educator, it is a life sentence.

Unexpectedly caught up in the HIV criminalization web at the age of 30, Mr. Suttle spent 6 months in a Louisiana state prison for a consensual sexual relationship with an adult partner. The crime? Not disclosing his HIV-positive status, a charge that Mr. Suttle says is untrue.

“I did disclose my status to my partner; however, I can’t really answer how they might have received it,” he said.

Today, at the age of 42, Mr. Suttle still carries the indelible stain of a conviction and of being a registered sex offender. “After their diagnosis, criminal charge, and/or conviction, many people think they’re done – either ‘I’ve gotten out of prison’ or ‘I’m still on probation’ – whatever the case may be,” he explained. “But we’re still living out these collateral consequences, be it with housing, moving to another state, or finding a job.”

The same is true for HIV-positive people who are charged and tried but manage to dodge prison for one reason or another. Monique Howell, a straight, 40-year-old former army soldier and single mother of five children, said that she was afraid to disclose her HIV status to a sexual partner but did advise him to wear a condom.* She points to her DD14 discharge papers (i.e., forms that verify that someone served in the military) that were issued when her military duty was rescinded following the dismissal of her court case.

“I was going to reenlist, but I got in trouble,” she said. She explained that although a DD14 separation helps to ensure that she can receive benefits and care, the papers were issued with a caveat stating “serious offense,” an indelible stain that, like Mr. Suttle’s, will follow her for the rest of her life.
 

Laws criminalize myths and misconceptions

HIV criminalization laws subject persons whose behaviors may expose others to HIV to felony or misdemeanor charges. Depending on the state, they can carry prison terms ranging from less than 10 years to life, according to the Centers for Disease Control and Prevention.

Originally enacted at the height of the AIDS epidemic in 1986, when fear was rampant and hundreds were dying, the laws were intended to reduce HIV transmission. But they’ve had unintended consequences: Amplifying stigmatization and discrimination and perpetuating HIV myths and misconceptions, including how HIV is transmitted.

Decades of scientific advances challenge the most basic reasoning behind laws (for example, that transmission is possible via biting or spitting or through a single sexual act, which studies have shown poses a risk as low as 0%-1.4%). In addition, few laws reflect one of the most important HIV research findings of the past decade: undetectable equals untransmittable, meaning that the virus cannot be sexually transmitted by people who are taking antiretroviral therapy and whose viral loads are undetectable.

In most of these cases, individuals who are positive for HIV are charged and punished for unintentional exposure, not deliberate intent to harm. Moreover, for the charge to stick, sexual partners don’t need to have acquired the virus or prove the transmission source if they do become HIV positive.

Ms. Howell noted that it was the Army that brought the charges against her, not her sexual partner at that time (who, incidentally, tested negative). He even testified on her behalf at the trial. “I’ll never forget it,” she said. “He said, ‘I don’t want anything to happen to Monique; even if you put her behind bars, she’s still HIV-positive and she’s still got those children. She told me to get a condom, and I chose not to.’ ”
 

Criminal vs. clinical fallout

In 2018, 20 scientists across the world issued a consensus statement underscoring the fact that HIV criminalization laws are based on fallacies and faulty science. The statement (which remains one of the most accessed in the Journal of the International AIDS Society) also points out that 33 countries (including the United States) use general criminal statutes such as attempted murder or reckless endangerment to lengthen sentences when people with HIV commit crimes.

When the laws were created, “many were the equivalent [to general criminal laws], because HIV was seen as a death sentence,” explained Chris Beyrer MD, MPH, professor of public health and human rights at Johns Hopkins Bloomberg School of Public Health, Baltimore. “So, failure to disclose your status, to wear a condom was seen as risking someone else’s life, which is no longer the case,” he added.

In fact, “from the perspective of the kinds of impact that these laws have had on transmission, or risk, or behavior, what you find is that they really have no public health benefit and they have real public harms,” said Dr. Beyrer.

Claire Farel, MD, assistant professor and medical director of the UNC Infectious Diseases Clinic at the University of North Carolina at Chapel Hill, concurs. “Because of the criminalization undercurrent, there are people who don’t get tested, meaning that they are at risk for worse health outcomes, such as cancer, vascular disease, and of course HIV-related poor outcomes, including progression to AIDS.”

Farel also points to the residual stigma associated with HIV. “Much of this is inextricable from that surrounding homophobia, especially among young men of color who have sex with men. It opens up a larger conversation that a lot of people don’t want to engage in,” she said.
 

Laws broaden existing disparities even further

The CDC released a study June 4 showing substantial declines in the overall incidence of HIV in the United States, with an important caveat: There’s been a worsening disparity in cases. Access to care and engagement with care remain poor among certain populations. For example, Black individuals accounted for 41% of new HIV infections in 2019, but they represent only 12% of the U.S. population; Hispanic/Latinx persons accounted for 29% of new infections, although they represent only 17% of the entire population.

The same is true for HIV criminalization: In 2020, more than 50% of defendants were people of color, according to U.S. case data collated by the HIV Justice Network.

Still, the momentum to change these antiquated laws is gaining speed. In May, the Illinois State Senate passed a bill repealing HIV criminalization, and this past March, Virginia’s Governor Ralph Northam signed a bill lowering HIV-related criminalization charges from a felony to a misdemeanor and changing the wording of its law to include both intent and transmission.** California, Colorado, Iowa, Michigan, Nevada, and North Carolina have also modernized or repealed their laws.
 

Ending the U.S. HIV epidemic: Patients first

Without true HIV criminalization reform, efforts to change the public and clinical mindset regarding HIV from its being a highly stigmatized disease to a preventable, treatable infection are likely to fall short. Dr. Beyrer emphasized that the onus lies with the scientific and activist communities working together. “I don’t know how you can end the epidemic if you are still stigmatizing the people who are actually acquiring these infections,” he said.

There are steps that patients can take while these forces push for change.

“As people first process their diagnosis, they need to learn as much about HIV and the science behind it as possible,” advised Mr. Suttle. He said that to protect oneself, it’s essential to learn about HIV criminalization and the laws in one’s state.

“Find someone you can trust, starting with your medical provider if possible, and if you have a significant other, bring that person to your appointments so they can see that you are in care and doing all that you can do to lower viral loads and protect others,” he added.

Ms. Howell said that although people should be in treatment and care, attitudes also need to change on the clinician side. “We’re just given these meds, told to take them, and are sent on our merry ways, but they don’t tell us how to live our lives properly; nobody grabs us and says, hey, these are the laws and you need to know this or that.”

When a person who is HIV positive does get caught up in the system, if possible, that person should consult an attorney who understands these laws. Mr. Suttle suggested reaching out to organizations in the movement to end HIV criminalization (e.g., the Sero Project, the Center for HIV Law and Policy, or the Positive Women’s Network) for further support, help with cases (including providing experts to testify), social services, and other resources. Mr. Suttle also encourages people who need help and direction to reach out to him directly at [email protected].

Forty years ago, the CDC published its first report of an illness in five healthy gay men living in Los Angeles. The first cases in women were reported shortly thereafter. Over the years, there have been many scientific advances in prevention and treatment. But as Dr. Beyrer aptly noted in an editorial published January 2021 in The Lancet HIV, “time has not lessened the sting of the early decades of AIDS.”

“We should not have to be afraid of who we are because we are HIV positive,” said Ms. Howell.

Dr. Farel, Mr. Suttle, and Ms. Howell report no relevant financial relationships. Dr. Beyrer has a consulting agreement with Merck.
 

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

*Correction, 6/14/2021: An earlier version of this story misstated Ms. Howell's age. She is 40.

**Correction, 6/14/2021: An earlier version of this story misspelled Gov. Northam's name.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.