TBD Meeting (2893-19)

SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.

It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.

The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.

The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.

The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).

A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.

As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.

Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.

So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.

“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.

Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm³.

The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.

[email protected]

SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.

SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.

It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.

The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.

The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.

The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).

A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.

As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.

Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.

So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.

“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.

Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm³.

The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.

[email protected]

SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.

SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.

It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.

The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.

The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.

The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).

A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.

As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.

Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.

So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.

“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.

Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm³.

The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.

[email protected]

SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.

SEATTLE – HIV infection is associated with increased risk of recurrent venous thromboembolism, especially within 1 year of the initial episode. The finding, presented during a poster session at the Conference on Retroviruses & Opportunistic Infections, follows up on an earlier study that found that first-time VTE risk also is higher among HIV-positive individuals than in the general population.

Jim Kling/MDedge News

The conclusion about first-time VTE risk, published earlier this year in Lancet HIV, came from a comparison between the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort and European population-level of studies of VTE. It found a crude incidence of 2.33 VTE events per 1,000 person-years In HIV patients, with heightened odds when CD4 cell counts were below 200 cells/mcL (adjusted hazard ratio, 3.40).

The new work represents a follow-up and compared results from ATHENA (153 patients with HIV and first VTE) and the Dutch MEGA cohort (4,005 patients without HIV, with first VTE), which includes the general population. Overall, 26% of patients in the ATHENA cohort experienced a second VTE event, compared with 16% of the general population. At 1 year after anticoagulation withdrawal, HIV-positive individuals were at 67% increased risk (HR, 1.67). At 6-years after withdrawal, the relationship was not statistically significant (HR, 1.22).

Researchers also found that CD4 cell-count recovery was associated with lowered risk, with every 100 cell-count increase between initial VTE diagnosis and anticoagulant withdrawal linked to a 20% reduction in risk (HR, 0.80).

“The clinical question is: If it’s true you have an increased risk of recurrence, should you be continuing anticoagulant therapy longer in people with HIV? This poster doesn’t answer that question and you probably need a randomized, controlled trial to look at that,” Peter Reiss, MD, professor of medicine at Amsterdam University Medical Center, said in an interview during the conference.

In the absence of a clear answer, it’s sensible for clinicians to be aware of the potential increased risk, much as clinicians have internalized the increased risk of atherosclerotic vascular disease in HIV patients. “I think the publication [in Lancet HIV] as well as this poster suggest that on the venous side of things there may also be an accentuated risk,” said Dr. Reiss.

Heidi Crane, MD, a professor of medicine at the University of Washington, Seattle, presented a poster examining the underlying factors that may predispose HIV patients to first-time VTE events. Her team performed an adjudicated review of VTE cases among HIV patients at six institutions and found that the risk factors appeared to be distinct from those seen in the general population.

The traditional long plane ride was less common in this population, while factors such as injected drug use and pneumonia were more common. The VTE events occurred at a median age of 49 years; 30% of the patients had a detectable viral load. “We’re seeing a little more (VTE) than you might expect, and in a younger population than you might have guessed,” said Dr. Crane in an interview.

The most frequent predisposing risk factors were recent hospitalization (40%), infection (40%), or immobilization/bed rest (24%) within the past 90 days, and injectable drug use (22%). “It’s not just the traditional risk factors. Some HIV-specific risk factors are driving this,” said Dr. Crane.

She also aims to learn more about the specifics of risk factors, such as catheter-associated thromboses. The team is working to increase the sample size in order to parse out the relationships with specific outcomes.

In the meantime, the data further characterize the health challenges facing people living with HIV. “This is another example demonstrating that comorbid conditions among patients with HIV that are often considered age related occur at much younger ages in our population,” said Dr. Crane.

SOURCE: Rokx C et al. CROI 2019, Abstract 636; and Tenforde MW et al. CROI 2019, Abstract 637.

.

SEATTLE – HIV infection is associated with increased risk of recurrent venous thromboembolism, especially within 1 year of the initial episode. The finding, presented during a poster session at the Conference on Retroviruses & Opportunistic Infections, follows up on an earlier study that found that first-time VTE risk also is higher among HIV-positive individuals than in the general population.

Jim Kling/MDedge News

The conclusion about first-time VTE risk, published earlier this year in Lancet HIV, came from a comparison between the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort and European population-level of studies of VTE. It found a crude incidence of 2.33 VTE events per 1,000 person-years In HIV patients, with heightened odds when CD4 cell counts were below 200 cells/mcL (adjusted hazard ratio, 3.40).

The new work represents a follow-up and compared results from ATHENA (153 patients with HIV and first VTE) and the Dutch MEGA cohort (4,005 patients without HIV, with first VTE), which includes the general population. Overall, 26% of patients in the ATHENA cohort experienced a second VTE event, compared with 16% of the general population. At 1 year after anticoagulation withdrawal, HIV-positive individuals were at 67% increased risk (HR, 1.67). At 6-years after withdrawal, the relationship was not statistically significant (HR, 1.22).

Researchers also found that CD4 cell-count recovery was associated with lowered risk, with every 100 cell-count increase between initial VTE diagnosis and anticoagulant withdrawal linked to a 20% reduction in risk (HR, 0.80).

“The clinical question is: If it’s true you have an increased risk of recurrence, should you be continuing anticoagulant therapy longer in people with HIV? This poster doesn’t answer that question and you probably need a randomized, controlled trial to look at that,” Peter Reiss, MD, professor of medicine at Amsterdam University Medical Center, said in an interview during the conference.

In the absence of a clear answer, it’s sensible for clinicians to be aware of the potential increased risk, much as clinicians have internalized the increased risk of atherosclerotic vascular disease in HIV patients. “I think the publication [in Lancet HIV] as well as this poster suggest that on the venous side of things there may also be an accentuated risk,” said Dr. Reiss.

Heidi Crane, MD, a professor of medicine at the University of Washington, Seattle, presented a poster examining the underlying factors that may predispose HIV patients to first-time VTE events. Her team performed an adjudicated review of VTE cases among HIV patients at six institutions and found that the risk factors appeared to be distinct from those seen in the general population.

The traditional long plane ride was less common in this population, while factors such as injected drug use and pneumonia were more common. The VTE events occurred at a median age of 49 years; 30% of the patients had a detectable viral load. “We’re seeing a little more (VTE) than you might expect, and in a younger population than you might have guessed,” said Dr. Crane in an interview.

The most frequent predisposing risk factors were recent hospitalization (40%), infection (40%), or immobilization/bed rest (24%) within the past 90 days, and injectable drug use (22%). “It’s not just the traditional risk factors. Some HIV-specific risk factors are driving this,” said Dr. Crane.

She also aims to learn more about the specifics of risk factors, such as catheter-associated thromboses. The team is working to increase the sample size in order to parse out the relationships with specific outcomes.

In the meantime, the data further characterize the health challenges facing people living with HIV. “This is another example demonstrating that comorbid conditions among patients with HIV that are often considered age related occur at much younger ages in our population,” said Dr. Crane.

SOURCE: Rokx C et al. CROI 2019, Abstract 636; and Tenforde MW et al. CROI 2019, Abstract 637.

.

SEATTLE – HIV infection is associated with increased risk of recurrent venous thromboembolism, especially within 1 year of the initial episode. The finding, presented during a poster session at the Conference on Retroviruses & Opportunistic Infections, follows up on an earlier study that found that first-time VTE risk also is higher among HIV-positive individuals than in the general population.

Jim Kling/MDedge News

The conclusion about first-time VTE risk, published earlier this year in Lancet HIV, came from a comparison between the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort and European population-level of studies of VTE. It found a crude incidence of 2.33 VTE events per 1,000 person-years In HIV patients, with heightened odds when CD4 cell counts were below 200 cells/mcL (adjusted hazard ratio, 3.40).

The new work represents a follow-up and compared results from ATHENA (153 patients with HIV and first VTE) and the Dutch MEGA cohort (4,005 patients without HIV, with first VTE), which includes the general population. Overall, 26% of patients in the ATHENA cohort experienced a second VTE event, compared with 16% of the general population. At 1 year after anticoagulation withdrawal, HIV-positive individuals were at 67% increased risk (HR, 1.67). At 6-years after withdrawal, the relationship was not statistically significant (HR, 1.22).

Researchers also found that CD4 cell-count recovery was associated with lowered risk, with every 100 cell-count increase between initial VTE diagnosis and anticoagulant withdrawal linked to a 20% reduction in risk (HR, 0.80).

“The clinical question is: If it’s true you have an increased risk of recurrence, should you be continuing anticoagulant therapy longer in people with HIV? This poster doesn’t answer that question and you probably need a randomized, controlled trial to look at that,” Peter Reiss, MD, professor of medicine at Amsterdam University Medical Center, said in an interview during the conference.

In the absence of a clear answer, it’s sensible for clinicians to be aware of the potential increased risk, much as clinicians have internalized the increased risk of atherosclerotic vascular disease in HIV patients. “I think the publication [in Lancet HIV] as well as this poster suggest that on the venous side of things there may also be an accentuated risk,” said Dr. Reiss.

Heidi Crane, MD, a professor of medicine at the University of Washington, Seattle, presented a poster examining the underlying factors that may predispose HIV patients to first-time VTE events. Her team performed an adjudicated review of VTE cases among HIV patients at six institutions and found that the risk factors appeared to be distinct from those seen in the general population.

The traditional long plane ride was less common in this population, while factors such as injected drug use and pneumonia were more common. The VTE events occurred at a median age of 49 years; 30% of the patients had a detectable viral load. “We’re seeing a little more (VTE) than you might expect, and in a younger population than you might have guessed,” said Dr. Crane in an interview.

The most frequent predisposing risk factors were recent hospitalization (40%), infection (40%), or immobilization/bed rest (24%) within the past 90 days, and injectable drug use (22%). “It’s not just the traditional risk factors. Some HIV-specific risk factors are driving this,” said Dr. Crane.

She also aims to learn more about the specifics of risk factors, such as catheter-associated thromboses. The team is working to increase the sample size in order to parse out the relationships with specific outcomes.

In the meantime, the data further characterize the health challenges facing people living with HIV. “This is another example demonstrating that comorbid conditions among patients with HIV that are often considered age related occur at much younger ages in our population,” said Dr. Crane.

SOURCE: Rokx C et al. CROI 2019, Abstract 636; and Tenforde MW et al. CROI 2019, Abstract 637.

.

SEATTLE – Antiretroviral therapy (ART) in the earliest weeks of life is associated with reduced time to suppression, according to a new study. Each week that treatment was delayed, patients had a 35% reduction in odds of achieving earlier viral load (VL) suppression.

damircudic/E+

Previous research had already shown that patients treated in the first year of life have better outcomes, including shortened time to viral suppression, and a lower reservoir size. Those studies looked at median age of ART start by month, and a review of the literature revealed that no research had been done on the first month.

The research was presented at the Conference on Retroviruses & Opportunistic Infections by Sara Domínguez Rodríguez, biostatistician and data manager in the pediatric infectious disease service at Hospital 12 Octubre, Madrid.

The researchers retrospectively analyzed 44 patients who were treated in the first 28 days of life, who had uninterrupted ART for at least 2 years, and who had VL measured at least twice during follow-up. Among these, 25 patients received ART in the first week, 19 in weeks 2-4. Patients treated prophylactically with AZT + 3TC (lamivudine) + NVP (nevirapine) any time in the first 15 days of life were considered treated at day 1.

Five of the patients were from the United Kingdom, 23 from Spain, 3 from Italy, and 13 from Thailand. Fifty-seven percent were girls; 35% were preterm. Patients treated in the first week had a higher log₁₀ HIV viral load at ART initiation (P = .02). There was no significant difference between the two groups with respect to CD4 count at ART initiation.

The time to suppression was not significantly different between the two groups, nor was the percentage of patients suppressed at various time points. Patients treated in the first week had reached suppression more often at 3 months and 6 months, but neither result reached statistical significance.

The small sample size of the study produced a challenge, and that led the team to consider suppression time and age as continuous variables. That revealed a curve that favored treatment in the first week of life: Each week of delay reduced the probability of achieving early viral suppression by 35% (hazard ratio, 0.65; 95% confidence interval, 0.46-0.92). “This means that if you delay the age at ART in terms of weeks, the probability of achieving suppression (over) time decreases, and this effect is particularly seen in the first year of follow-up,” Dr. Domínguez Rodríguez said in an interview.

Some might have concerns that treating children too early could have adverse effects. This study, though small, showed promising results. “You might think if you treat very early, maybe the child will not tolerate the medicine or keep on with the treatment, and we saw no difference. So that supports treating early,” senior author Pablo Rojo Conejo, PhD, an infectious disease specialist at Hospital 12 de Octubre, said in an interview.

Others in attendance found the results encouraging. “It’s very good news to see that early starting impacts the life of these children,” Filipe de Barros Perini, MD, head of care and treatment of the HIV program at the Brazilian Ministry of Health, said in an interview.

SOURCE: Domínguez Rodríguez S et al. CROI 2019, Abstract 44.

SEATTLE – Antiretroviral therapy (ART) in the earliest weeks of life is associated with reduced time to suppression, according to a new study. Each week that treatment was delayed, patients had a 35% reduction in odds of achieving earlier viral load (VL) suppression.

damircudic/E+

Previous research had already shown that patients treated in the first year of life have better outcomes, including shortened time to viral suppression, and a lower reservoir size. Those studies looked at median age of ART start by month, and a review of the literature revealed that no research had been done on the first month.

The research was presented at the Conference on Retroviruses & Opportunistic Infections by Sara Domínguez Rodríguez, biostatistician and data manager in the pediatric infectious disease service at Hospital 12 Octubre, Madrid.

The researchers retrospectively analyzed 44 patients who were treated in the first 28 days of life, who had uninterrupted ART for at least 2 years, and who had VL measured at least twice during follow-up. Among these, 25 patients received ART in the first week, 19 in weeks 2-4. Patients treated prophylactically with AZT + 3TC (lamivudine) + NVP (nevirapine) any time in the first 15 days of life were considered treated at day 1.

Five of the patients were from the United Kingdom, 23 from Spain, 3 from Italy, and 13 from Thailand. Fifty-seven percent were girls; 35% were preterm. Patients treated in the first week had a higher log₁₀ HIV viral load at ART initiation (P = .02). There was no significant difference between the two groups with respect to CD4 count at ART initiation.

The time to suppression was not significantly different between the two groups, nor was the percentage of patients suppressed at various time points. Patients treated in the first week had reached suppression more often at 3 months and 6 months, but neither result reached statistical significance.

The small sample size of the study produced a challenge, and that led the team to consider suppression time and age as continuous variables. That revealed a curve that favored treatment in the first week of life: Each week of delay reduced the probability of achieving early viral suppression by 35% (hazard ratio, 0.65; 95% confidence interval, 0.46-0.92). “This means that if you delay the age at ART in terms of weeks, the probability of achieving suppression (over) time decreases, and this effect is particularly seen in the first year of follow-up,” Dr. Domínguez Rodríguez said in an interview.

Some might have concerns that treating children too early could have adverse effects. This study, though small, showed promising results. “You might think if you treat very early, maybe the child will not tolerate the medicine or keep on with the treatment, and we saw no difference. So that supports treating early,” senior author Pablo Rojo Conejo, PhD, an infectious disease specialist at Hospital 12 de Octubre, said in an interview.

Others in attendance found the results encouraging. “It’s very good news to see that early starting impacts the life of these children,” Filipe de Barros Perini, MD, head of care and treatment of the HIV program at the Brazilian Ministry of Health, said in an interview.

SOURCE: Domínguez Rodríguez S et al. CROI 2019, Abstract 44.

SEATTLE – Antiretroviral therapy (ART) in the earliest weeks of life is associated with reduced time to suppression, according to a new study. Each week that treatment was delayed, patients had a 35% reduction in odds of achieving earlier viral load (VL) suppression.

damircudic/E+

Previous research had already shown that patients treated in the first year of life have better outcomes, including shortened time to viral suppression, and a lower reservoir size. Those studies looked at median age of ART start by month, and a review of the literature revealed that no research had been done on the first month.

The research was presented at the Conference on Retroviruses & Opportunistic Infections by Sara Domínguez Rodríguez, biostatistician and data manager in the pediatric infectious disease service at Hospital 12 Octubre, Madrid.

The researchers retrospectively analyzed 44 patients who were treated in the first 28 days of life, who had uninterrupted ART for at least 2 years, and who had VL measured at least twice during follow-up. Among these, 25 patients received ART in the first week, 19 in weeks 2-4. Patients treated prophylactically with AZT + 3TC (lamivudine) + NVP (nevirapine) any time in the first 15 days of life were considered treated at day 1.

Five of the patients were from the United Kingdom, 23 from Spain, 3 from Italy, and 13 from Thailand. Fifty-seven percent were girls; 35% were preterm. Patients treated in the first week had a higher log₁₀ HIV viral load at ART initiation (P = .02). There was no significant difference between the two groups with respect to CD4 count at ART initiation.

The time to suppression was not significantly different between the two groups, nor was the percentage of patients suppressed at various time points. Patients treated in the first week had reached suppression more often at 3 months and 6 months, but neither result reached statistical significance.

The small sample size of the study produced a challenge, and that led the team to consider suppression time and age as continuous variables. That revealed a curve that favored treatment in the first week of life: Each week of delay reduced the probability of achieving early viral suppression by 35% (hazard ratio, 0.65; 95% confidence interval, 0.46-0.92). “This means that if you delay the age at ART in terms of weeks, the probability of achieving suppression (over) time decreases, and this effect is particularly seen in the first year of follow-up,” Dr. Domínguez Rodríguez said in an interview.

Some might have concerns that treating children too early could have adverse effects. This study, though small, showed promising results. “You might think if you treat very early, maybe the child will not tolerate the medicine or keep on with the treatment, and we saw no difference. So that supports treating early,” senior author Pablo Rojo Conejo, PhD, an infectious disease specialist at Hospital 12 de Octubre, said in an interview.

Others in attendance found the results encouraging. “It’s very good news to see that early starting impacts the life of these children,” Filipe de Barros Perini, MD, head of care and treatment of the HIV program at the Brazilian Ministry of Health, said in an interview.

SOURCE: Domínguez Rodríguez S et al. CROI 2019, Abstract 44.

SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.

M. Alexander Otto/MDedge News

Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.

An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.

He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.

Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.

M. Alexander Otto/MDedge News

Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.

Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.

The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.

The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.

The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.

Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.

The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.

He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.

There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.

[email protected]

SOURCE: Gupta RK et al. CROI 2019, Abstract 29.

SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.

M. Alexander Otto/MDedge News

Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.

An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.

He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.

Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.

M. Alexander Otto/MDedge News

Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.

Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.

The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.

The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.

The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.

Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.

The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.

He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.

There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.

[email protected]

SOURCE: Gupta RK et al. CROI 2019, Abstract 29.

SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.

M. Alexander Otto/MDedge News

Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.

An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.

He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.

Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.

M. Alexander Otto/MDedge News

Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.

Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.

The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.

The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.

The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.

Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.

The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.

He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.

There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.

[email protected]

SOURCE: Gupta RK et al. CROI 2019, Abstract 29.

SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.

Wavebreakmedia Ltd/ThinkStockPhotos.com

The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.

Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.

The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.

She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.

The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m³ (39% vs. 26%).

A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).

Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log¹⁰ copies/mL), CD4+ cell count less than 200 cells/m³ (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).

Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).

The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.

SOURCE: Torgersen J et al. CROI 2019, Abstract 90.

SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.

Wavebreakmedia Ltd/ThinkStockPhotos.com

The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.

Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.

The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.

She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.

The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m³ (39% vs. 26%).

A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).

Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log¹⁰ copies/mL), CD4+ cell count less than 200 cells/m³ (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).

Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).

The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.

SOURCE: Torgersen J et al. CROI 2019, Abstract 90.

SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.

Wavebreakmedia Ltd/ThinkStockPhotos.com

The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.

Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.

The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.

She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.

The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m³ (39% vs. 26%).

A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).

Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log¹⁰ copies/mL), CD4+ cell count less than 200 cells/m³ (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).

Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).

The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.

SOURCE: Torgersen J et al. CROI 2019, Abstract 90.

SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, randomized trial involving more than 5,000 men at high risk for the infection.

M. Alexander Otto/MDedge News

Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.

F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.

The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.

The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.

More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.

There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.

When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.

One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.

For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.

On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m² in the F/TDF arm, but rose 1.8 mL/min per 1.73 m² in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.

There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.

In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.

“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”

It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.

The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.

The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.

[email protected]

SOURCE: Hare CB et al. CROI 2019, Abstract 104 LB.

SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, randomized trial involving more than 5,000 men at high risk for the infection.

M. Alexander Otto/MDedge News

Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.

F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.

The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.

The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.

More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.

There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.

When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.

One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.

For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.

On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m² in the F/TDF arm, but rose 1.8 mL/min per 1.73 m² in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.

There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.

In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.

“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”

It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.

The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.

The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.

[email protected]

SOURCE: Hare CB et al. CROI 2019, Abstract 104 LB.

SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, randomized trial involving more than 5,000 men at high risk for the infection.

M. Alexander Otto/MDedge News

Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.

F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.

The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.

The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.

More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.

There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.

When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.

One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.

For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.

On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m² in the F/TDF arm, but rose 1.8 mL/min per 1.73 m² in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.

There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.

In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.

“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”

It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.

The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.

The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.

[email protected]

SOURCE: Hare CB et al. CROI 2019, Abstract 104 LB.

SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.

MattZ90/Thinkstock.com

“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,” Mark Mirochnick, MD, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.

Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observed during a study in Botswana led both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.

It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.

The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.

Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).

Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.

A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).

There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.

The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.

SOURCE: Mark Mirochnick et al. CROI 2019, Abstract 39 LB.

SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.

MattZ90/Thinkstock.com

“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,” Mark Mirochnick, MD, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.

Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observed during a study in Botswana led both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.

It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.

The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.

Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).

Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.

A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).

There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.

The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.

SOURCE: Mark Mirochnick et al. CROI 2019, Abstract 39 LB.

SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.

MattZ90/Thinkstock.com

“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,” Mark Mirochnick, MD, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.

Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observed during a study in Botswana led both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.

It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.

The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.

Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).

Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.

A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).

There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.

The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.

SOURCE: Mark Mirochnick et al. CROI 2019, Abstract 39 LB.

SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.

M.Alexander Otto/MDedge News

“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.

To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.

There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.

Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).

Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.

Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.

The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.

M. Alexander Otto//MDedge News

That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.

“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.

[email protected]

SOURCE: Bosh KA et al. CROI 2019, Abstract 147.

SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.

M.Alexander Otto/MDedge News

“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.

To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.

There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.

Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).

Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.

Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.

The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.

M. Alexander Otto//MDedge News

That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.

“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.

[email protected]

SOURCE: Bosh KA et al. CROI 2019, Abstract 147.

SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.

M.Alexander Otto/MDedge News

“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.

To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.

There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.

Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).

Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.

Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.

The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.

M. Alexander Otto//MDedge News

That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.

“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.

[email protected]

SOURCE: Bosh KA et al. CROI 2019, Abstract 147.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.

Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.

The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.

The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.

COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).

The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.

The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.

“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.

The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.

“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.

The National Institutes of Health funded the work. Dr. Crothers had no disclosures.

[email protected]

SOURCE: Crothers K et al. CROI 2019, Abstract 31.

SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.

Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.

The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.

The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.

COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).

The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.

The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.

“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.

The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.

“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.

The National Institutes of Health funded the work. Dr. Crothers had no disclosures.

[email protected]

SOURCE: Crothers K et al. CROI 2019, Abstract 31.

SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.

Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.

The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.

The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.

COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).

The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.

The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.

“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.

The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.

“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.

The National Institutes of Health funded the work. Dr. Crothers had no disclosures.

[email protected]

SOURCE: Crothers K et al. CROI 2019, Abstract 31.