HIV

People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.

“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .

“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.

Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.

Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.

Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.

All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.

The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
 

Virologic suppression well maintained

At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.

Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.

These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.

“This study supports the use of B/F/TAF as a first-line agent for people living with HIV who carry the M184V/I resistance mutation,” added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
 

Easy to administer, well tolerated, and potent

Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”

“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.

Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.

“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.

“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.

“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.

The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.

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

People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.

“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .

“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.

Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.

Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.

Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.

All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.

The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
 

Virologic suppression well maintained

At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.

Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.

These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.

“This study supports the use of B/F/TAF as a first-line agent for people living with HIV who carry the M184V/I resistance mutation,” added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
 

Easy to administer, well tolerated, and potent

Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”

“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.

Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.

“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.

“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.

“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.

The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.

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

People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.

“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .

“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.

Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.

Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.

Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.

All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.

The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
 

Virologic suppression well maintained

At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.

Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.

These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.

“This study supports the use of B/F/TAF as a first-line agent for people living with HIV who carry the M184V/I resistance mutation,” added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
 

Easy to administer, well tolerated, and potent

Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”

“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.

Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.

“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.

“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.

“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.

The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

In recent years, increased use of integrase strand transferase inhibitor (INSTI) antiviral treatment (ART) has raised concerns about weight gain and adverse outcomes in patients with HIV. This is especially true regarding possible excessive gestational weight gain, which in women without HIV has been associated with maternal gestational diabetes, hypertensive and liver conditions, as well as related risks for preterm birth, fetal macrosomia, and higher weight after birth. 

Unfortunately, few studies in pregnant women with HIV have moved out of the controlled environment into real-world settings, potentially limiting current knowledge about the impact of gestational weight gain – as well as strategies to both prevent it and the associated adverse outcomes.

That is what a team of infectious disease specialists at the Hospital Federal dos Servidores do Estado in Rio de Janeiro recently sought to answer among a cohort of INSTI-experienced and INSTI-naive women with BMIs less than 25 kg/m² (underweight/normal weight) and higher than 25 kg/m².
 

Surprising findings

The investigators determined that rates of excessive weight gain were significantly higher in INSTI-naive women with BMI less than 25 who experienced rates as high as 31.6%, compared with approximately 12% of women who conceived while on INSTIs, regardless of BMI values at baseline (P = .004). 

However, rates of unfavorable pregnancy outcomes (for example, small for gestational age, preterm birth, stillbirth, death) appeared to be low overall and similar among all the study groups.

“We had some discussions when we were working on this and thought that the weight gain might have adverse effects,” Trevon Fuller, PhD, lead author and a postdoctoral student at the Hospital Federal dos Servidores do Estado, told this news organization.

“But it looked like the weight gain might actually be good, to the extent that we didn’t see any harm to the mom or the baby of those underweight or normal weight women who were naive to INSTIs,” he explained.

Dr. Fuller and his team enrolled 198 pregnant women living with HIV who sought care at the Hospital Federal dos Servidores do Estado – a national reference center for USAID’s Prevention of Mother to Child Transmission strategic program – between October 2014 and October 2021.

Participants were divided into two primary cohorts: BMI less than 25 at enrollment (n = 74) or BMI of 25 or higher (n = 124), then further divided by timing of INSTI-based combined ART: 

• INSTI-naive: women using INSTI-based ART (raltegravir [Isentress] 400 mg twice per day or dolutegravir [Tivicay] 50 mg/day plus 2 non-nucleoside reverse transcriptase inhibitors – lamivudine plus tenofovir disoproxil fumarate or lamivudine plus zidovudine) for 4 weeks between baseline and near delivery.
• INSTI-experienced: women who became pregnant while using INSTIs for at least 6 months before conception. 

Among underweight/normal weight participants, 77% (n = 57) were INSTI-naive and 23% (n = 17) INSTI-experienced, and among overweight/obese participants, 81.5% (n = 101) were INSTI-naive, and 18.5% (n = 23) were experienced.

Maternal age, which did not differ significantly by BMI or treatment experience, was a median of 28 years, and most participants were non-White. All participants were virally suppressed near delivery.

Study findings, which were published online  in HIV Medicine, highlighted that median weight near delivery in participants who were overweight/obese at baseline was similar regardless of whether they were treatment-experienced (90 kg [198 lb]) or treatment-naive (82.3 kg [181 lb]), P = .026.

However, participants who were underweight/normal weight who were INSTI-naive had significantly higher rates of gestational weight gain (31.5%, 18/57), compared with those of underweight/normal weight who were INSTI-experienced (11.8%, 2/17), P = .004. Notably, this gain was significant in all categories of change (that is, low < 0.18 kg/week, normal 0.18-0.59 kg/week), and high > 0.59 kg/week).

“One of the things that we took away was that this weight gain is primarily happening with women who are starting INSTIs,” said Dr. Fuller. 

“The data suggest that [it] might be temporary in the sense that there’s not going to be continuous weight gain but that it will probably approach some type of horizontal asymptote,” he added.

Although obstetric and neonatal outcomes were secondary measures, the investigators did not observe any significantly different outcomes when comparing the groups, and there were no stillbirths, neonatal deaths, or macrosomia.

Preterm delivery rates in underweight/normal weight participants who were INSTI-experienced (11.8%, 2/17) and INSTI-naive (5.3%, 3/57) were similar to overweight/obese participants who were INSTI-experienced (13%, 3/23) and INSTI-naive (6.9%, 7/101).

The same was true for low birthweight.

Still, the study appears to raise more questions than it answers, Sigal Yawetz, MD, an infectious disease specialist at Brigham and Women’s Hospital, Boston, said in an interview – a factor that she said is common also in some of the more recent randomized controlled studies, such as IMPAACT PROMISE.

Dr. Yawetz, who was not involved in the study, also noted, “The groups were small, so comparisons within the groups are difficult, and so many people were excluded that it’s hard to know if there were adverse outcomes related to this ... It’s very confounded.”

The World Health Organization estimates that there are roughly 1.3 million pregnant women with HIV, 81% of whom are on antiretroviral therapy. Although the literature continues to evolve, data suggest that in general, Black women are at greater risk for gestational weight gain.

“We have to remember that women who gain excess weight in pregnancy are still going to be with this weight following pregnancy as well,” Dr. Yawetz said. “So, it might impact their pregnancy but also their health after delivery and for subsequent pregnancies, which we don’t have data for yet.”

Dr. Fuller agrees that more data are needed and mentioned that the team plans to study this further, ideally with larger sample sizes.

Yet, despite the lingering questions, there is a silver lining, one that Dr. Yawetz was emphatic about.

“I really welcome people doing studies on this because we really need the data. By far, integrase inhibitors are the first-line regimen all over the world for pregnant women, and if you look at the gestalt or full picture, this is the best regimen to give pregnant women,” she said.

Dr. Fuller and Dr. Yawetz report no relevant financial relationships. The study was independently supported.

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

In recent years, increased use of integrase strand transferase inhibitor (INSTI) antiviral treatment (ART) has raised concerns about weight gain and adverse outcomes in patients with HIV. This is especially true regarding possible excessive gestational weight gain, which in women without HIV has been associated with maternal gestational diabetes, hypertensive and liver conditions, as well as related risks for preterm birth, fetal macrosomia, and higher weight after birth. 

Unfortunately, few studies in pregnant women with HIV have moved out of the controlled environment into real-world settings, potentially limiting current knowledge about the impact of gestational weight gain – as well as strategies to both prevent it and the associated adverse outcomes.

That is what a team of infectious disease specialists at the Hospital Federal dos Servidores do Estado in Rio de Janeiro recently sought to answer among a cohort of INSTI-experienced and INSTI-naive women with BMIs less than 25 kg/m² (underweight/normal weight) and higher than 25 kg/m².
 

Surprising findings

The investigators determined that rates of excessive weight gain were significantly higher in INSTI-naive women with BMI less than 25 who experienced rates as high as 31.6%, compared with approximately 12% of women who conceived while on INSTIs, regardless of BMI values at baseline (P = .004). 

However, rates of unfavorable pregnancy outcomes (for example, small for gestational age, preterm birth, stillbirth, death) appeared to be low overall and similar among all the study groups.

“We had some discussions when we were working on this and thought that the weight gain might have adverse effects,” Trevon Fuller, PhD, lead author and a postdoctoral student at the Hospital Federal dos Servidores do Estado, told this news organization.

“But it looked like the weight gain might actually be good, to the extent that we didn’t see any harm to the mom or the baby of those underweight or normal weight women who were naive to INSTIs,” he explained.

Dr. Fuller and his team enrolled 198 pregnant women living with HIV who sought care at the Hospital Federal dos Servidores do Estado – a national reference center for USAID’s Prevention of Mother to Child Transmission strategic program – between October 2014 and October 2021.

Participants were divided into two primary cohorts: BMI less than 25 at enrollment (n = 74) or BMI of 25 or higher (n = 124), then further divided by timing of INSTI-based combined ART: 

• INSTI-naive: women using INSTI-based ART (raltegravir [Isentress] 400 mg twice per day or dolutegravir [Tivicay] 50 mg/day plus 2 non-nucleoside reverse transcriptase inhibitors – lamivudine plus tenofovir disoproxil fumarate or lamivudine plus zidovudine) for 4 weeks between baseline and near delivery.
• INSTI-experienced: women who became pregnant while using INSTIs for at least 6 months before conception. 

Among underweight/normal weight participants, 77% (n = 57) were INSTI-naive and 23% (n = 17) INSTI-experienced, and among overweight/obese participants, 81.5% (n = 101) were INSTI-naive, and 18.5% (n = 23) were experienced.

Maternal age, which did not differ significantly by BMI or treatment experience, was a median of 28 years, and most participants were non-White. All participants were virally suppressed near delivery.

Study findings, which were published online  in HIV Medicine, highlighted that median weight near delivery in participants who were overweight/obese at baseline was similar regardless of whether they were treatment-experienced (90 kg [198 lb]) or treatment-naive (82.3 kg [181 lb]), P = .026.

However, participants who were underweight/normal weight who were INSTI-naive had significantly higher rates of gestational weight gain (31.5%, 18/57), compared with those of underweight/normal weight who were INSTI-experienced (11.8%, 2/17), P = .004. Notably, this gain was significant in all categories of change (that is, low < 0.18 kg/week, normal 0.18-0.59 kg/week), and high > 0.59 kg/week).

“One of the things that we took away was that this weight gain is primarily happening with women who are starting INSTIs,” said Dr. Fuller. 

“The data suggest that [it] might be temporary in the sense that there’s not going to be continuous weight gain but that it will probably approach some type of horizontal asymptote,” he added.

Although obstetric and neonatal outcomes were secondary measures, the investigators did not observe any significantly different outcomes when comparing the groups, and there were no stillbirths, neonatal deaths, or macrosomia.

Preterm delivery rates in underweight/normal weight participants who were INSTI-experienced (11.8%, 2/17) and INSTI-naive (5.3%, 3/57) were similar to overweight/obese participants who were INSTI-experienced (13%, 3/23) and INSTI-naive (6.9%, 7/101).

The same was true for low birthweight.

Still, the study appears to raise more questions than it answers, Sigal Yawetz, MD, an infectious disease specialist at Brigham and Women’s Hospital, Boston, said in an interview – a factor that she said is common also in some of the more recent randomized controlled studies, such as IMPAACT PROMISE.

Dr. Yawetz, who was not involved in the study, also noted, “The groups were small, so comparisons within the groups are difficult, and so many people were excluded that it’s hard to know if there were adverse outcomes related to this ... It’s very confounded.”

The World Health Organization estimates that there are roughly 1.3 million pregnant women with HIV, 81% of whom are on antiretroviral therapy. Although the literature continues to evolve, data suggest that in general, Black women are at greater risk for gestational weight gain.

“We have to remember that women who gain excess weight in pregnancy are still going to be with this weight following pregnancy as well,” Dr. Yawetz said. “So, it might impact their pregnancy but also their health after delivery and for subsequent pregnancies, which we don’t have data for yet.”

Dr. Fuller agrees that more data are needed and mentioned that the team plans to study this further, ideally with larger sample sizes.

Yet, despite the lingering questions, there is a silver lining, one that Dr. Yawetz was emphatic about.

“I really welcome people doing studies on this because we really need the data. By far, integrase inhibitors are the first-line regimen all over the world for pregnant women, and if you look at the gestalt or full picture, this is the best regimen to give pregnant women,” she said.

Dr. Fuller and Dr. Yawetz report no relevant financial relationships. The study was independently supported.

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

In recent years, increased use of integrase strand transferase inhibitor (INSTI) antiviral treatment (ART) has raised concerns about weight gain and adverse outcomes in patients with HIV. This is especially true regarding possible excessive gestational weight gain, which in women without HIV has been associated with maternal gestational diabetes, hypertensive and liver conditions, as well as related risks for preterm birth, fetal macrosomia, and higher weight after birth. 

Unfortunately, few studies in pregnant women with HIV have moved out of the controlled environment into real-world settings, potentially limiting current knowledge about the impact of gestational weight gain – as well as strategies to both prevent it and the associated adverse outcomes.

That is what a team of infectious disease specialists at the Hospital Federal dos Servidores do Estado in Rio de Janeiro recently sought to answer among a cohort of INSTI-experienced and INSTI-naive women with BMIs less than 25 kg/m² (underweight/normal weight) and higher than 25 kg/m².
 

Surprising findings

The investigators determined that rates of excessive weight gain were significantly higher in INSTI-naive women with BMI less than 25 who experienced rates as high as 31.6%, compared with approximately 12% of women who conceived while on INSTIs, regardless of BMI values at baseline (P = .004). 

However, rates of unfavorable pregnancy outcomes (for example, small for gestational age, preterm birth, stillbirth, death) appeared to be low overall and similar among all the study groups.

“We had some discussions when we were working on this and thought that the weight gain might have adverse effects,” Trevon Fuller, PhD, lead author and a postdoctoral student at the Hospital Federal dos Servidores do Estado, told this news organization.

“But it looked like the weight gain might actually be good, to the extent that we didn’t see any harm to the mom or the baby of those underweight or normal weight women who were naive to INSTIs,” he explained.

Dr. Fuller and his team enrolled 198 pregnant women living with HIV who sought care at the Hospital Federal dos Servidores do Estado – a national reference center for USAID’s Prevention of Mother to Child Transmission strategic program – between October 2014 and October 2021.

Participants were divided into two primary cohorts: BMI less than 25 at enrollment (n = 74) or BMI of 25 or higher (n = 124), then further divided by timing of INSTI-based combined ART: 

• INSTI-naive: women using INSTI-based ART (raltegravir [Isentress] 400 mg twice per day or dolutegravir [Tivicay] 50 mg/day plus 2 non-nucleoside reverse transcriptase inhibitors – lamivudine plus tenofovir disoproxil fumarate or lamivudine plus zidovudine) for 4 weeks between baseline and near delivery.
• INSTI-experienced: women who became pregnant while using INSTIs for at least 6 months before conception. 

Among underweight/normal weight participants, 77% (n = 57) were INSTI-naive and 23% (n = 17) INSTI-experienced, and among overweight/obese participants, 81.5% (n = 101) were INSTI-naive, and 18.5% (n = 23) were experienced.

Maternal age, which did not differ significantly by BMI or treatment experience, was a median of 28 years, and most participants were non-White. All participants were virally suppressed near delivery.

Study findings, which were published online  in HIV Medicine, highlighted that median weight near delivery in participants who were overweight/obese at baseline was similar regardless of whether they were treatment-experienced (90 kg [198 lb]) or treatment-naive (82.3 kg [181 lb]), P = .026.

However, participants who were underweight/normal weight who were INSTI-naive had significantly higher rates of gestational weight gain (31.5%, 18/57), compared with those of underweight/normal weight who were INSTI-experienced (11.8%, 2/17), P = .004. Notably, this gain was significant in all categories of change (that is, low < 0.18 kg/week, normal 0.18-0.59 kg/week), and high > 0.59 kg/week).

“One of the things that we took away was that this weight gain is primarily happening with women who are starting INSTIs,” said Dr. Fuller. 

“The data suggest that [it] might be temporary in the sense that there’s not going to be continuous weight gain but that it will probably approach some type of horizontal asymptote,” he added.

Although obstetric and neonatal outcomes were secondary measures, the investigators did not observe any significantly different outcomes when comparing the groups, and there were no stillbirths, neonatal deaths, or macrosomia.

Preterm delivery rates in underweight/normal weight participants who were INSTI-experienced (11.8%, 2/17) and INSTI-naive (5.3%, 3/57) were similar to overweight/obese participants who were INSTI-experienced (13%, 3/23) and INSTI-naive (6.9%, 7/101).

The same was true for low birthweight.

Still, the study appears to raise more questions than it answers, Sigal Yawetz, MD, an infectious disease specialist at Brigham and Women’s Hospital, Boston, said in an interview – a factor that she said is common also in some of the more recent randomized controlled studies, such as IMPAACT PROMISE.

Dr. Yawetz, who was not involved in the study, also noted, “The groups were small, so comparisons within the groups are difficult, and so many people were excluded that it’s hard to know if there were adverse outcomes related to this ... It’s very confounded.”

The World Health Organization estimates that there are roughly 1.3 million pregnant women with HIV, 81% of whom are on antiretroviral therapy. Although the literature continues to evolve, data suggest that in general, Black women are at greater risk for gestational weight gain.

“We have to remember that women who gain excess weight in pregnancy are still going to be with this weight following pregnancy as well,” Dr. Yawetz said. “So, it might impact their pregnancy but also their health after delivery and for subsequent pregnancies, which we don’t have data for yet.”

Dr. Fuller agrees that more data are needed and mentioned that the team plans to study this further, ideally with larger sample sizes.

Yet, despite the lingering questions, there is a silver lining, one that Dr. Yawetz was emphatic about.

“I really welcome people doing studies on this because we really need the data. By far, integrase inhibitors are the first-line regimen all over the world for pregnant women, and if you look at the gestalt or full picture, this is the best regimen to give pregnant women,” she said.

Dr. Fuller and Dr. Yawetz report no relevant financial relationships. The study was independently supported.

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

Fort Worth, Tex. – A case decision made by Texas U.S. District Judge Reed Charles O’Connor that will allow employers to deny health care insurance coverage for HIV preexposure prophylaxis (PrEP) is already provoking HIV activists, medical associations, nonprofits, and patients.

As this news organization first reported in August, the class action suit (Kelley v. Azar) has a broader goal – to dismantle the Affordable Care Act using the argument that many of the preventive services it covers, including PrEP, violate the Religious Freedom Restoration Act.

“Judge O’Connor has a long history of issuing rulings against the Affordable Care Act and LGBT individuals, and we expect the case to be successfully appealed as has been the case with his previous discriminatory decisions,” said Carl Schmid, executive director of the HIV+Hepatitis Policy Institute in Washington, in a prepared statement issued shortly after the ruling.

“To single out PrEP, which are FDA approved drugs that effectively prevent HIV, and conclude that its coverage violates the religious freedom of certain individuals, is plain wrong, highly discriminatory, and impedes the public health of our nation,” he said. 

PrEP is not just for men who have sex with men. According to the Centers for Disease Control and Prevention, more than 1 million Americans could benefit from PrEP, and roughly 20% are heterosexual women – a fact both Mr. Schmid and the HIV Medicine Association pointed out in response to Judge O’Connor’s ruling.

“Denying access to PrEP threatens the health of more than 1.2 million Americans who could benefit from this potentially life saving intervention,” stated Marwan Haddad, MD, MPH, chair of the HIV Medicine Association, in a press release issued by the organization.

“This ruling is yet one more instance of unacceptable interference in scientific, evidence-based health care practices that must remain within the sanctity of the provider-patient relationship,” she said.

The ruling is also outside what is normally considered religious “conscientious objection.”

While the American Medical Association supports the rights of physicians to act in accordance with conscience, medical ethicists like Abram Brummett, PhD, assistant professor, department of foundational medical studies, Oakland University, Rochester, Mich., previously told this news organization that this ruling actually reflects a phenomenon known as “conscience creep” – that is, the way conscientious objection creeps outside traditional contexts like abortion, sterilization, and organ transplantation.

Incidentally, the case is not yet completed; Judge O’Connor still has to decide on challenges to contraceptives and HPV mandates. He has requested that defendants and plaintiffs file a supplemental briefing before he makes a final decision.

Regardless of how it plays out, it is unclear whether the U.S. Department of Health and Human Services will appeal.

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

Fort Worth, Tex. – A case decision made by Texas U.S. District Judge Reed Charles O’Connor that will allow employers to deny health care insurance coverage for HIV preexposure prophylaxis (PrEP) is already provoking HIV activists, medical associations, nonprofits, and patients.

As this news organization first reported in August, the class action suit (Kelley v. Azar) has a broader goal – to dismantle the Affordable Care Act using the argument that many of the preventive services it covers, including PrEP, violate the Religious Freedom Restoration Act.

“Judge O’Connor has a long history of issuing rulings against the Affordable Care Act and LGBT individuals, and we expect the case to be successfully appealed as has been the case with his previous discriminatory decisions,” said Carl Schmid, executive director of the HIV+Hepatitis Policy Institute in Washington, in a prepared statement issued shortly after the ruling.

“To single out PrEP, which are FDA approved drugs that effectively prevent HIV, and conclude that its coverage violates the religious freedom of certain individuals, is plain wrong, highly discriminatory, and impedes the public health of our nation,” he said. 

PrEP is not just for men who have sex with men. According to the Centers for Disease Control and Prevention, more than 1 million Americans could benefit from PrEP, and roughly 20% are heterosexual women – a fact both Mr. Schmid and the HIV Medicine Association pointed out in response to Judge O’Connor’s ruling.

“Denying access to PrEP threatens the health of more than 1.2 million Americans who could benefit from this potentially life saving intervention,” stated Marwan Haddad, MD, MPH, chair of the HIV Medicine Association, in a press release issued by the organization.

“This ruling is yet one more instance of unacceptable interference in scientific, evidence-based health care practices that must remain within the sanctity of the provider-patient relationship,” she said.

The ruling is also outside what is normally considered religious “conscientious objection.”

While the American Medical Association supports the rights of physicians to act in accordance with conscience, medical ethicists like Abram Brummett, PhD, assistant professor, department of foundational medical studies, Oakland University, Rochester, Mich., previously told this news organization that this ruling actually reflects a phenomenon known as “conscience creep” – that is, the way conscientious objection creeps outside traditional contexts like abortion, sterilization, and organ transplantation.

Incidentally, the case is not yet completed; Judge O’Connor still has to decide on challenges to contraceptives and HPV mandates. He has requested that defendants and plaintiffs file a supplemental briefing before he makes a final decision.

Regardless of how it plays out, it is unclear whether the U.S. Department of Health and Human Services will appeal.

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

Fort Worth, Tex. – A case decision made by Texas U.S. District Judge Reed Charles O’Connor that will allow employers to deny health care insurance coverage for HIV preexposure prophylaxis (PrEP) is already provoking HIV activists, medical associations, nonprofits, and patients.

As this news organization first reported in August, the class action suit (Kelley v. Azar) has a broader goal – to dismantle the Affordable Care Act using the argument that many of the preventive services it covers, including PrEP, violate the Religious Freedom Restoration Act.

“Judge O’Connor has a long history of issuing rulings against the Affordable Care Act and LGBT individuals, and we expect the case to be successfully appealed as has been the case with his previous discriminatory decisions,” said Carl Schmid, executive director of the HIV+Hepatitis Policy Institute in Washington, in a prepared statement issued shortly after the ruling.

“To single out PrEP, which are FDA approved drugs that effectively prevent HIV, and conclude that its coverage violates the religious freedom of certain individuals, is plain wrong, highly discriminatory, and impedes the public health of our nation,” he said. 

PrEP is not just for men who have sex with men. According to the Centers for Disease Control and Prevention, more than 1 million Americans could benefit from PrEP, and roughly 20% are heterosexual women – a fact both Mr. Schmid and the HIV Medicine Association pointed out in response to Judge O’Connor’s ruling.

“Denying access to PrEP threatens the health of more than 1.2 million Americans who could benefit from this potentially life saving intervention,” stated Marwan Haddad, MD, MPH, chair of the HIV Medicine Association, in a press release issued by the organization.

“This ruling is yet one more instance of unacceptable interference in scientific, evidence-based health care practices that must remain within the sanctity of the provider-patient relationship,” she said.

The ruling is also outside what is normally considered religious “conscientious objection.”

While the American Medical Association supports the rights of physicians to act in accordance with conscience, medical ethicists like Abram Brummett, PhD, assistant professor, department of foundational medical studies, Oakland University, Rochester, Mich., previously told this news organization that this ruling actually reflects a phenomenon known as “conscience creep” – that is, the way conscientious objection creeps outside traditional contexts like abortion, sterilization, and organ transplantation.

Incidentally, the case is not yet completed; Judge O’Connor still has to decide on challenges to contraceptives and HPV mandates. He has requested that defendants and plaintiffs file a supplemental briefing before he makes a final decision.

Regardless of how it plays out, it is unclear whether the U.S. Department of Health and Human Services will appeal.

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

A dolutegravir-based treatment regimen holds its own as a first choice of antiretroviral therapy (ART) for pregnant individuals, based on data from more than 1,200 patients.

“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.

In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.

The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.

The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.

The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.

“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.

Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.

A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.

“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.

“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.

The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.

However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
 

Findings fill a key research gap

The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.

Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.

The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.

The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”

Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.

The researchers and Dr. Badell had no financial conflicts to disclose.

A dolutegravir-based treatment regimen holds its own as a first choice of antiretroviral therapy (ART) for pregnant individuals, based on data from more than 1,200 patients.

“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.

In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.

The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.

The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.

The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.

“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.

Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.

A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.

“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.

“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.

The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.

However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
 

Findings fill a key research gap

The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.

Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.

The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.

The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”

Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.

The researchers and Dr. Badell had no financial conflicts to disclose.

A dolutegravir-based treatment regimen holds its own as a first choice of antiretroviral therapy (ART) for pregnant individuals, based on data from more than 1,200 patients.

“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.

In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.

The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.

The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.

The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.

“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.

Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.

A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.

“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.

“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.

The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.

However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
 

Findings fill a key research gap

The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.

Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.

The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.

The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”

Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.

The researchers and Dr. Badell had no financial conflicts to disclose.

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

In this issue:

• Vaccinations
• Mental Health and Related Disorders
• LGBTQ+ Veterans
• Military Sexual Trauma
• Sleep Disorders
• Respiratory Illnesses
• HIV Care in the VA
• Rheumatologic Diseases
• The Cancer-Obesity Connection
• Skin Health for Active-Duty Personnel
• Contraception
• Chronic Kidney Disease
• Cardiovascular Diseases
• Neurologic Disorders
• Hearing, Vision, and Balance

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

In this issue:

• Vaccinations
• Mental Health and Related Disorders
• LGBTQ+ Veterans
• Military Sexual Trauma
• Sleep Disorders
• Respiratory Illnesses
• HIV Care in the VA
• Rheumatologic Diseases
• The Cancer-Obesity Connection
• Skin Health for Active-Duty Personnel
• Contraception
• Chronic Kidney Disease
• Cardiovascular Diseases
• Neurologic Disorders
• Hearing, Vision, and Balance

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

In this issue:

• Vaccinations
• Mental Health and Related Disorders
• LGBTQ+ Veterans
• Military Sexual Trauma
• Sleep Disorders
• Respiratory Illnesses
• HIV Care in the VA
• Rheumatologic Diseases
• The Cancer-Obesity Connection
• Skin Health for Active-Duty Personnel
• Contraception
• Chronic Kidney Disease
• Cardiovascular Diseases
• Neurologic Disorders
• Hearing, Vision, and Balance

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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