CROI 2016

BOSTON – The risk that a person living in the United States will become infected with HIV in his or her lifetime is declining compared with a decade ago, but the risk remains quite high among blacks and Hispanics/Latinos, investigators from the Centers for Disease Control and Prevention caution.

In fact, an estimated one in two black men who have sex with men (MSM) and one in four Hispanic/Latino MSM will be diagnosed with HIV within their lifetimes, reported CDC investigator Dr. Kristen Hess, at a media briefing and in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

“In the current analysis, we estimated that the overall lifetime risk is 1 in 99, which is reduced from 1 in 78 in the previous estimate [2004-2005]. However, there are vast disparities that still persist,” she said.

Estimates of lifetime risk are frequently used by epidemiologists to compare the burden of diseases such as cancer across populations, but are infrequently used for estimating lifetime risk of HIV infection, Dr. Hess said.

“The advantage to using lifetime risk is that it is more easily understood by the general population. Therefore, it could be a useful tool for clinicians, outreach workers, and policy makers,” she said in her podium presentation.

Previous estimates of lifetime HIV infection risk were based on data from 2004 and 2005, before data from all 50 states were available, leading the investigators to calculate new estimates based on more current information.

They drew on the National HIV Surveillance System for information about HIV diagnosis, mortality data from the National Center for Health Statistics, and U.S. Census data on population size by age, race/ethnicity, and state. The study covered the years 2009 through 2013.

The investigators used the number of HIV diagnoses and the number of non-HIV deaths to calculate the probability of a diagnosis of HIV at a given age and applied the probabilities to a hypothetical cohort to determine risk estimates.

They defined lifetime risk as” the cumulative probability of being diagnosed with HIV from birth.”

The lifetime risk of an HIV diagnosis for MSM varied widely by race/ethnicity. Overall, 1 in 64 men will be diagnosed with HIV during his lifetime, with the risk highest for black men at 1 in 20, followed by Hispanics at 1 in 48, native Hawaiian or other Pacific Islanders (NHOPI) at 1 in 82, American Indian/Alaskan Natives (AI/AN) at 1 in 129, whites at 1 in 132, and Asians with the lowest risk at 1 in 174.

For women the risks were considerably lower overall at 1 in 227. However, African American women had the same level of risk as Hispanic MSM (1 in 48). Risks for other racial/ethnic groups among women are: Hispanics, 1 in 227; NHOPI, 1 in 385; AI/AN, 1 in 399; whites, 1 in 880; and Asians, 1 in 883.

Lifetime risk from age 13 of an HIV diagnosis by risk group was highest among MSM, at 1 in 6, followed by female injectable drug users (1 in 23), male injectable drug users (1 in 36), heterosexual women (1 in 241), and heterosexual men (1 in 473).

Among MSM, the risk was highest for black men (1 in 2), followed by Hispanic/Latino (1 in 4), NHOPI (1 in 7), white (1 in 11), AI/AN (1 in 12) and Asians (1 in 14).

The overall lifetime risk of an HIV diagnosis among the U.S. population as a whole was 1 in 99. The area with the highest lifetime risk was Washington, D.C., with a risk of 1 in 13. Dr. Hess cautioned that the D.C. is a city, not a state, which could skew comparisons. The states with the highest lifetime HIV infection risk were Maryland, Georgia, and Florida, and in general, the highest lifetime risks were in the South.

The lowest overall risk was in North Dakota, at 1 in 670.

The investigators noted that their study was limited by its reliance on diagnosis rather than incidence data and may thus underestimate some risk categories because infection may occur several years before a diagnosis. Additionally, death certificates may be missing HIV information, she said.

“One of the goals of National HIV/AIDS strategy is to reduce disparities. Lifetime risk highlights work that still needs to be done and could be used to track progress toward this goal,” Dr. Hess said.

The study was supported by the CDC. Dr. Hess is a CDC employee.

BOSTON – The risk that a person living in the United States will become infected with HIV in his or her lifetime is declining compared with a decade ago, but the risk remains quite high among blacks and Hispanics/Latinos, investigators from the Centers for Disease Control and Prevention caution.

In fact, an estimated one in two black men who have sex with men (MSM) and one in four Hispanic/Latino MSM will be diagnosed with HIV within their lifetimes, reported CDC investigator Dr. Kristen Hess, at a media briefing and in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

“In the current analysis, we estimated that the overall lifetime risk is 1 in 99, which is reduced from 1 in 78 in the previous estimate [2004-2005]. However, there are vast disparities that still persist,” she said.

Estimates of lifetime risk are frequently used by epidemiologists to compare the burden of diseases such as cancer across populations, but are infrequently used for estimating lifetime risk of HIV infection, Dr. Hess said.

“The advantage to using lifetime risk is that it is more easily understood by the general population. Therefore, it could be a useful tool for clinicians, outreach workers, and policy makers,” she said in her podium presentation.

Previous estimates of lifetime HIV infection risk were based on data from 2004 and 2005, before data from all 50 states were available, leading the investigators to calculate new estimates based on more current information.

They drew on the National HIV Surveillance System for information about HIV diagnosis, mortality data from the National Center for Health Statistics, and U.S. Census data on population size by age, race/ethnicity, and state. The study covered the years 2009 through 2013.

The investigators used the number of HIV diagnoses and the number of non-HIV deaths to calculate the probability of a diagnosis of HIV at a given age and applied the probabilities to a hypothetical cohort to determine risk estimates.

They defined lifetime risk as” the cumulative probability of being diagnosed with HIV from birth.”

The lifetime risk of an HIV diagnosis for MSM varied widely by race/ethnicity. Overall, 1 in 64 men will be diagnosed with HIV during his lifetime, with the risk highest for black men at 1 in 20, followed by Hispanics at 1 in 48, native Hawaiian or other Pacific Islanders (NHOPI) at 1 in 82, American Indian/Alaskan Natives (AI/AN) at 1 in 129, whites at 1 in 132, and Asians with the lowest risk at 1 in 174.

For women the risks were considerably lower overall at 1 in 227. However, African American women had the same level of risk as Hispanic MSM (1 in 48). Risks for other racial/ethnic groups among women are: Hispanics, 1 in 227; NHOPI, 1 in 385; AI/AN, 1 in 399; whites, 1 in 880; and Asians, 1 in 883.

Lifetime risk from age 13 of an HIV diagnosis by risk group was highest among MSM, at 1 in 6, followed by female injectable drug users (1 in 23), male injectable drug users (1 in 36), heterosexual women (1 in 241), and heterosexual men (1 in 473).

Among MSM, the risk was highest for black men (1 in 2), followed by Hispanic/Latino (1 in 4), NHOPI (1 in 7), white (1 in 11), AI/AN (1 in 12) and Asians (1 in 14).

The overall lifetime risk of an HIV diagnosis among the U.S. population as a whole was 1 in 99. The area with the highest lifetime risk was Washington, D.C., with a risk of 1 in 13. Dr. Hess cautioned that the D.C. is a city, not a state, which could skew comparisons. The states with the highest lifetime HIV infection risk were Maryland, Georgia, and Florida, and in general, the highest lifetime risks were in the South.

The lowest overall risk was in North Dakota, at 1 in 670.

The investigators noted that their study was limited by its reliance on diagnosis rather than incidence data and may thus underestimate some risk categories because infection may occur several years before a diagnosis. Additionally, death certificates may be missing HIV information, she said.

“One of the goals of National HIV/AIDS strategy is to reduce disparities. Lifetime risk highlights work that still needs to be done and could be used to track progress toward this goal,” Dr. Hess said.

The study was supported by the CDC. Dr. Hess is a CDC employee.

BOSTON – The risk that a person living in the United States will become infected with HIV in his or her lifetime is declining compared with a decade ago, but the risk remains quite high among blacks and Hispanics/Latinos, investigators from the Centers for Disease Control and Prevention caution.

In fact, an estimated one in two black men who have sex with men (MSM) and one in four Hispanic/Latino MSM will be diagnosed with HIV within their lifetimes, reported CDC investigator Dr. Kristen Hess, at a media briefing and in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

“In the current analysis, we estimated that the overall lifetime risk is 1 in 99, which is reduced from 1 in 78 in the previous estimate [2004-2005]. However, there are vast disparities that still persist,” she said.

Estimates of lifetime risk are frequently used by epidemiologists to compare the burden of diseases such as cancer across populations, but are infrequently used for estimating lifetime risk of HIV infection, Dr. Hess said.

“The advantage to using lifetime risk is that it is more easily understood by the general population. Therefore, it could be a useful tool for clinicians, outreach workers, and policy makers,” she said in her podium presentation.

Previous estimates of lifetime HIV infection risk were based on data from 2004 and 2005, before data from all 50 states were available, leading the investigators to calculate new estimates based on more current information.

They drew on the National HIV Surveillance System for information about HIV diagnosis, mortality data from the National Center for Health Statistics, and U.S. Census data on population size by age, race/ethnicity, and state. The study covered the years 2009 through 2013.

The investigators used the number of HIV diagnoses and the number of non-HIV deaths to calculate the probability of a diagnosis of HIV at a given age and applied the probabilities to a hypothetical cohort to determine risk estimates.

They defined lifetime risk as” the cumulative probability of being diagnosed with HIV from birth.”

The lifetime risk of an HIV diagnosis for MSM varied widely by race/ethnicity. Overall, 1 in 64 men will be diagnosed with HIV during his lifetime, with the risk highest for black men at 1 in 20, followed by Hispanics at 1 in 48, native Hawaiian or other Pacific Islanders (NHOPI) at 1 in 82, American Indian/Alaskan Natives (AI/AN) at 1 in 129, whites at 1 in 132, and Asians with the lowest risk at 1 in 174.

For women the risks were considerably lower overall at 1 in 227. However, African American women had the same level of risk as Hispanic MSM (1 in 48). Risks for other racial/ethnic groups among women are: Hispanics, 1 in 227; NHOPI, 1 in 385; AI/AN, 1 in 399; whites, 1 in 880; and Asians, 1 in 883.

Lifetime risk from age 13 of an HIV diagnosis by risk group was highest among MSM, at 1 in 6, followed by female injectable drug users (1 in 23), male injectable drug users (1 in 36), heterosexual women (1 in 241), and heterosexual men (1 in 473).

Among MSM, the risk was highest for black men (1 in 2), followed by Hispanic/Latino (1 in 4), NHOPI (1 in 7), white (1 in 11), AI/AN (1 in 12) and Asians (1 in 14).

The overall lifetime risk of an HIV diagnosis among the U.S. population as a whole was 1 in 99. The area with the highest lifetime risk was Washington, D.C., with a risk of 1 in 13. Dr. Hess cautioned that the D.C. is a city, not a state, which could skew comparisons. The states with the highest lifetime HIV infection risk were Maryland, Georgia, and Florida, and in general, the highest lifetime risks were in the South.

The lowest overall risk was in North Dakota, at 1 in 670.

The investigators noted that their study was limited by its reliance on diagnosis rather than incidence data and may thus underestimate some risk categories because infection may occur several years before a diagnosis. Additionally, death certificates may be missing HIV information, she said.

“One of the goals of National HIV/AIDS strategy is to reduce disparities. Lifetime risk highlights work that still needs to be done and could be used to track progress toward this goal,” Dr. Hess said.

The study was supported by the CDC. Dr. Hess is a CDC employee.

BOSTON – Getting people who are infected with HIV onto early antiretroviral therapy (ART) and keeping them on it may be the best way to reduce HIV-related deaths and simplify the care continuum or “cascade,” said investigators who advocate universal, immediate ART eligibility and access.

A study of HIV deaths and care patterns in four African countries, presented at the Conference on Retroviruses and Opportunistic Infections, suggests that HIV deaths could be reduced significantly if patients have early therapeutic intervention and remain in care.

“We’re all very aware that the provision of antiretroviral therapy has dramatically reduced mortality from HIV in sub-Saharan Africa, but data from population cohort studies in Eastern and Southern Africa show us that mortality rates among HIV positive adults still remain three to six times greater than HIV-negative adults in settings with mature ART programs. So the question that we set out to answer was why do these HIV deaths still continue to occur in settings where ART is widely available?” said coinvestigator Dr. Jeffrey Eaton from Imperial College London.

Dr. Eaton and his colleagues conducted a study to identify the stages in the care cascade where most deaths occur, in the hope of pinpointing targets for interventions that have could have the greatest effect on improving care.

To do this, they designed a study to model the previous HIV care experience of people who died from the infection. They reviewed empirical data from clinical and vital statistic registries from Western Cape, South Africa, and from population cohorts in Uganda, Malawi, and South Africa.

For example, death registration records from South Africa linked to clinical records for 3,161 adult HIV deaths in 2011 showed that 25% of patients were either not diagnosed or not linked to care, 35% never started on ART, 10% had been on ART for less than 6 months, 20% were lost from ART care or had a gap longer than 3 months in the past year, and just 10% were continuously in care.

The investigators also analyzed data from four mathematical models that were calibrated to HIV epidemics and to patterns of care and utilization of treatment in Kenya, Malawi, Rwanda and South Africa. All four models estimated how HIV deaths were distributed across each stage of care, and projected the distribution over the next 10 years, with the assumption that current patterns of HIV care use and retention would be continued. In addition, three of the models simulated what would happen if all patients linked to care were started on immediate ART therapy.

Dr. Eaton and his colleagues examined the care cascade from the time of HIV diagnosis, linkage to care, pre–antiretroviral therapy care, ART initiation, and survival and retention on ART.

‘Dramatic declines in HIV deaths’

“All of the models simulated the dramatic declines in HIV deaths as treatments became available, and the models also indicated that persons who have initiated ART understandably account for an increasing proportion of HIV deaths going into the future. But the projections estimate that 25%-40% of HIV deaths will continue to be among persons never initiated on ART,” Dr. Eaton said.

Looking at HIV death across the care cascade, the models indicated that only 10%-30% of HIV-related deaths would likely occur among patients who are continuously on

©MattZ90/Thinkstock.com

“ART for 6 months or more. Deaths among HIV-positive people who were disengaged from care were projected to account for a “substantial” proportion of all HIV deaths in all four models – from 21%-44% of all HIV deaths projected for 2025.

If present conditions were to continue, the models predict, from 9%-22% of HIV deaths from 2016 through 2025 would occur in patients who were linked to care but for one reason or another were never started on ART.

The models project immediate ART initiation could reduce HIV deaths by between 6%-14% during 2016-2025, mostly by removing opportunities for patients to disengage before treatment initiation, rather than by direct prevention or therapeutic benefits of early ART, the investigators stated.

Their findings suggest that “indicators based on monitoring the effectiveness of ART among patients in clinics miss this population [of patients never diagnosed or linked to care], and thus we feel are insufficient for evaluating the overall effectiveness of ART programs,” Dr. Eaton said.

An HIV/AIDS specialist who was not involved in the study commented in an interview that Dr. Eaton’s approach is an innovative way to identify gaps in care that can contribute to HIV-related deaths.

“Some big points that I came away with were that people who know their [HIV] status but are not in care, that’s contributing to mortality, and then as we get people more into care, mortality is going to accrue if and when people fall out of care,” said Dr. Diane Havlir of the University of California, San Francisco.

Dr. Havlir moderated a media briefing where Dr. Eaton discussed his data following his presentation in an oral abstract session.

The study was supported by the Bill and Melinda Gates Foundation. Dr. Eaton and Dr. Havlir reported having no commercial interests relevant to the study.

BOSTON – Getting people who are infected with HIV onto early antiretroviral therapy (ART) and keeping them on it may be the best way to reduce HIV-related deaths and simplify the care continuum or “cascade,” said investigators who advocate universal, immediate ART eligibility and access.

A study of HIV deaths and care patterns in four African countries, presented at the Conference on Retroviruses and Opportunistic Infections, suggests that HIV deaths could be reduced significantly if patients have early therapeutic intervention and remain in care.

“We’re all very aware that the provision of antiretroviral therapy has dramatically reduced mortality from HIV in sub-Saharan Africa, but data from population cohort studies in Eastern and Southern Africa show us that mortality rates among HIV positive adults still remain three to six times greater than HIV-negative adults in settings with mature ART programs. So the question that we set out to answer was why do these HIV deaths still continue to occur in settings where ART is widely available?” said coinvestigator Dr. Jeffrey Eaton from Imperial College London.

Dr. Eaton and his colleagues conducted a study to identify the stages in the care cascade where most deaths occur, in the hope of pinpointing targets for interventions that have could have the greatest effect on improving care.

To do this, they designed a study to model the previous HIV care experience of people who died from the infection. They reviewed empirical data from clinical and vital statistic registries from Western Cape, South Africa, and from population cohorts in Uganda, Malawi, and South Africa.

For example, death registration records from South Africa linked to clinical records for 3,161 adult HIV deaths in 2011 showed that 25% of patients were either not diagnosed or not linked to care, 35% never started on ART, 10% had been on ART for less than 6 months, 20% were lost from ART care or had a gap longer than 3 months in the past year, and just 10% were continuously in care.

The investigators also analyzed data from four mathematical models that were calibrated to HIV epidemics and to patterns of care and utilization of treatment in Kenya, Malawi, Rwanda and South Africa. All four models estimated how HIV deaths were distributed across each stage of care, and projected the distribution over the next 10 years, with the assumption that current patterns of HIV care use and retention would be continued. In addition, three of the models simulated what would happen if all patients linked to care were started on immediate ART therapy.

Dr. Eaton and his colleagues examined the care cascade from the time of HIV diagnosis, linkage to care, pre–antiretroviral therapy care, ART initiation, and survival and retention on ART.

‘Dramatic declines in HIV deaths’

“All of the models simulated the dramatic declines in HIV deaths as treatments became available, and the models also indicated that persons who have initiated ART understandably account for an increasing proportion of HIV deaths going into the future. But the projections estimate that 25%-40% of HIV deaths will continue to be among persons never initiated on ART,” Dr. Eaton said.

Looking at HIV death across the care cascade, the models indicated that only 10%-30% of HIV-related deaths would likely occur among patients who are continuously on

©MattZ90/Thinkstock.com

“ART for 6 months or more. Deaths among HIV-positive people who were disengaged from care were projected to account for a “substantial” proportion of all HIV deaths in all four models – from 21%-44% of all HIV deaths projected for 2025.

If present conditions were to continue, the models predict, from 9%-22% of HIV deaths from 2016 through 2025 would occur in patients who were linked to care but for one reason or another were never started on ART.

The models project immediate ART initiation could reduce HIV deaths by between 6%-14% during 2016-2025, mostly by removing opportunities for patients to disengage before treatment initiation, rather than by direct prevention or therapeutic benefits of early ART, the investigators stated.

Their findings suggest that “indicators based on monitoring the effectiveness of ART among patients in clinics miss this population [of patients never diagnosed or linked to care], and thus we feel are insufficient for evaluating the overall effectiveness of ART programs,” Dr. Eaton said.

An HIV/AIDS specialist who was not involved in the study commented in an interview that Dr. Eaton’s approach is an innovative way to identify gaps in care that can contribute to HIV-related deaths.

“Some big points that I came away with were that people who know their [HIV] status but are not in care, that’s contributing to mortality, and then as we get people more into care, mortality is going to accrue if and when people fall out of care,” said Dr. Diane Havlir of the University of California, San Francisco.

Dr. Havlir moderated a media briefing where Dr. Eaton discussed his data following his presentation in an oral abstract session.

The study was supported by the Bill and Melinda Gates Foundation. Dr. Eaton and Dr. Havlir reported having no commercial interests relevant to the study.

BOSTON – Getting people who are infected with HIV onto early antiretroviral therapy (ART) and keeping them on it may be the best way to reduce HIV-related deaths and simplify the care continuum or “cascade,” said investigators who advocate universal, immediate ART eligibility and access.

A study of HIV deaths and care patterns in four African countries, presented at the Conference on Retroviruses and Opportunistic Infections, suggests that HIV deaths could be reduced significantly if patients have early therapeutic intervention and remain in care.

“We’re all very aware that the provision of antiretroviral therapy has dramatically reduced mortality from HIV in sub-Saharan Africa, but data from population cohort studies in Eastern and Southern Africa show us that mortality rates among HIV positive adults still remain three to six times greater than HIV-negative adults in settings with mature ART programs. So the question that we set out to answer was why do these HIV deaths still continue to occur in settings where ART is widely available?” said coinvestigator Dr. Jeffrey Eaton from Imperial College London.

Dr. Eaton and his colleagues conducted a study to identify the stages in the care cascade where most deaths occur, in the hope of pinpointing targets for interventions that have could have the greatest effect on improving care.

To do this, they designed a study to model the previous HIV care experience of people who died from the infection. They reviewed empirical data from clinical and vital statistic registries from Western Cape, South Africa, and from population cohorts in Uganda, Malawi, and South Africa.

For example, death registration records from South Africa linked to clinical records for 3,161 adult HIV deaths in 2011 showed that 25% of patients were either not diagnosed or not linked to care, 35% never started on ART, 10% had been on ART for less than 6 months, 20% were lost from ART care or had a gap longer than 3 months in the past year, and just 10% were continuously in care.

The investigators also analyzed data from four mathematical models that were calibrated to HIV epidemics and to patterns of care and utilization of treatment in Kenya, Malawi, Rwanda and South Africa. All four models estimated how HIV deaths were distributed across each stage of care, and projected the distribution over the next 10 years, with the assumption that current patterns of HIV care use and retention would be continued. In addition, three of the models simulated what would happen if all patients linked to care were started on immediate ART therapy.

Dr. Eaton and his colleagues examined the care cascade from the time of HIV diagnosis, linkage to care, pre–antiretroviral therapy care, ART initiation, and survival and retention on ART.

‘Dramatic declines in HIV deaths’

“All of the models simulated the dramatic declines in HIV deaths as treatments became available, and the models also indicated that persons who have initiated ART understandably account for an increasing proportion of HIV deaths going into the future. But the projections estimate that 25%-40% of HIV deaths will continue to be among persons never initiated on ART,” Dr. Eaton said.

Looking at HIV death across the care cascade, the models indicated that only 10%-30% of HIV-related deaths would likely occur among patients who are continuously on

©MattZ90/Thinkstock.com

“ART for 6 months or more. Deaths among HIV-positive people who were disengaged from care were projected to account for a “substantial” proportion of all HIV deaths in all four models – from 21%-44% of all HIV deaths projected for 2025.

If present conditions were to continue, the models predict, from 9%-22% of HIV deaths from 2016 through 2025 would occur in patients who were linked to care but for one reason or another were never started on ART.

The models project immediate ART initiation could reduce HIV deaths by between 6%-14% during 2016-2025, mostly by removing opportunities for patients to disengage before treatment initiation, rather than by direct prevention or therapeutic benefits of early ART, the investigators stated.

Their findings suggest that “indicators based on monitoring the effectiveness of ART among patients in clinics miss this population [of patients never diagnosed or linked to care], and thus we feel are insufficient for evaluating the overall effectiveness of ART programs,” Dr. Eaton said.

An HIV/AIDS specialist who was not involved in the study commented in an interview that Dr. Eaton’s approach is an innovative way to identify gaps in care that can contribute to HIV-related deaths.

“Some big points that I came away with were that people who know their [HIV] status but are not in care, that’s contributing to mortality, and then as we get people more into care, mortality is going to accrue if and when people fall out of care,” said Dr. Diane Havlir of the University of California, San Francisco.

Dr. Havlir moderated a media briefing where Dr. Eaton discussed his data following his presentation in an oral abstract session.

The study was supported by the Bill and Melinda Gates Foundation. Dr. Eaton and Dr. Havlir reported having no commercial interests relevant to the study.

BOSTON – Optimally treated patients with HIV are living longer than ever, and have narrowed but not completely closed the gap in life expectancy with their uninfected peers, investigators in a large cohort study reported.

In 1996, a 20-year-old infected with HIV could expect to live only 19 more years, to age 39. In 2011, the additional life expectancy for a 20-year-old HIV-positive subject was 53 years, meaning that given survival to age 20, he or she could expect to live to age 73, said Julia L. Marcus, Ph.D., from Kaiser Permanente Northern California in Oakland.

She and her colleagues studied life expectancy in a cohort of nearly 25,000 Kaiser Permanente California members who were HIV-positive and more than 250,000 HIV-negative members in an effort to better delineate differences in survival by HIV status than in earlier comparisons.

“This is the first study to our knowledge to directly compare life expectancy by HIV status, accounting for individual-level factors and access to health care. We have complete ascertainment of deaths, and therefore no loss to follow-up, and our results are generalizable to the broader insured population,” Dr. Marcus said at the Conference on Retroviruses and Opportunistic Infections.

The study results reflect the remarkable improvement in care of insured HIV-positive patients with the introduction of antiretroviral therapy (ART), which has allowed more than half of all HIV-positive individuals to live to age 50 or older, she said.

Previous studies suggesting that there is still a gap in life expectancy between HIV-positive and HIV-negative people had compared HIV-positive individuals with the general population, limiting their ability to account for differences in life expectancy by HIV status because of differences in sociodemographic factors, access to care, and risk factors that may affect survival, Dr. Marcus said.

To overcome these limitations, the investigators compared life expectancies for 24,768 HIV-positive people who were members of Kaiser Permanente California at any time from 1996 through 2011 with those of 257,600 HIV-negative members.

They conducted estimates by year of study follow-up, sex, race/ethnicity, HIV risk group, CD4 counts at ART initiation, and by key modifiable risk factors including viral hepatitis, drug and alcohol abuse, and smoking.

They found that over the course of the study, mortality rates among HIV-negative members remained relatively stable, at 439 per 100,000 person-years (py) in 1996, to 381/100,000 in 2011. In contrast, there was a steep decline among HIV-positive members, from 7,077/100,000 py in 1996, to 1,054/100,000 py in 2011.

Among women, remaining life expectancy at age 20 among those who were HIV-negative was 65 years in 1996, and 64 in 2011. In contrast, HIV-positive women saw an increase from 37 years in 1996 to 51 in 2011. Yet at the latest time point, there was still a 13-year gap in expectancy between HIV-negative and HIV-positive women.

Among HIV-negative men at age 20, additional life expectancy remained at 62 years throughout the study period, whereas among HIV-positive men it improved from 38 years in 1996 to 49 years in 2011. But here, too, there remained a 13-year gap in expectancy between HIV-positive and HIV-negative subjects.

An analysis of life expectancies at age 20 by race/ethnicity showed similar significant gains throughout the study period for whites, blacks, and Hispanics (P less than .0010), although HIV-positive whites and Hispanics did slightly but significantly better than blacks (P = .007 and .001, respectively),

There were also significant gains in life expectancy among men having sex with men, from 40 years in 1996 to 51 years in 2011, heterosexuals, from 38 years to 51 years, and among injectable drug users, from 36 to 46 years.

To see whether they could account for the 13-year gap that remained between HIV-positive and HIV-negative members, the authors looked at various care- and disease-related factors. When they considered those patients who received optimal therapy, with ART initiated when their CD4 counts were 500 or above, the expectancy gap narrowed to 7.9 years.

When they controlled for patients without hepatitis B or C infections, the gap narrowed to 7.2 years. HIV-positive patients with no drug or alcohol abuse had only 6.8 years less life expectancy than their HIV-negative counterparts, and those who did not smoke had only a 5.4 year life-expectancy decrement.

In the question-and-answer session following Dr. Marcus’ talk, an attendee suggested that some of the remaining gap may be explained by mental health differences between HIV-positive and HIV-negative patients.

“I would urge that you start looking at mental health issues and depression in particular, which is both vastly more common in people with HIV, and also has a demonstrable impact on mortality. That may explain some of the gap,” he said.

Dr. Marcus agreed about the importance of looking at this question, and noted that it is being actively explored in ongoing studies.

Dr. Marcus disclosed that she has been supported by a research grant to her institution from Merck.

BOSTON – Optimally treated patients with HIV are living longer than ever, and have narrowed but not completely closed the gap in life expectancy with their uninfected peers, investigators in a large cohort study reported.

In 1996, a 20-year-old infected with HIV could expect to live only 19 more years, to age 39. In 2011, the additional life expectancy for a 20-year-old HIV-positive subject was 53 years, meaning that given survival to age 20, he or she could expect to live to age 73, said Julia L. Marcus, Ph.D., from Kaiser Permanente Northern California in Oakland.

She and her colleagues studied life expectancy in a cohort of nearly 25,000 Kaiser Permanente California members who were HIV-positive and more than 250,000 HIV-negative members in an effort to better delineate differences in survival by HIV status than in earlier comparisons.

“This is the first study to our knowledge to directly compare life expectancy by HIV status, accounting for individual-level factors and access to health care. We have complete ascertainment of deaths, and therefore no loss to follow-up, and our results are generalizable to the broader insured population,” Dr. Marcus said at the Conference on Retroviruses and Opportunistic Infections.

The study results reflect the remarkable improvement in care of insured HIV-positive patients with the introduction of antiretroviral therapy (ART), which has allowed more than half of all HIV-positive individuals to live to age 50 or older, she said.

Previous studies suggesting that there is still a gap in life expectancy between HIV-positive and HIV-negative people had compared HIV-positive individuals with the general population, limiting their ability to account for differences in life expectancy by HIV status because of differences in sociodemographic factors, access to care, and risk factors that may affect survival, Dr. Marcus said.

To overcome these limitations, the investigators compared life expectancies for 24,768 HIV-positive people who were members of Kaiser Permanente California at any time from 1996 through 2011 with those of 257,600 HIV-negative members.

They conducted estimates by year of study follow-up, sex, race/ethnicity, HIV risk group, CD4 counts at ART initiation, and by key modifiable risk factors including viral hepatitis, drug and alcohol abuse, and smoking.

They found that over the course of the study, mortality rates among HIV-negative members remained relatively stable, at 439 per 100,000 person-years (py) in 1996, to 381/100,000 in 2011. In contrast, there was a steep decline among HIV-positive members, from 7,077/100,000 py in 1996, to 1,054/100,000 py in 2011.

Among women, remaining life expectancy at age 20 among those who were HIV-negative was 65 years in 1996, and 64 in 2011. In contrast, HIV-positive women saw an increase from 37 years in 1996 to 51 in 2011. Yet at the latest time point, there was still a 13-year gap in expectancy between HIV-negative and HIV-positive women.

Among HIV-negative men at age 20, additional life expectancy remained at 62 years throughout the study period, whereas among HIV-positive men it improved from 38 years in 1996 to 49 years in 2011. But here, too, there remained a 13-year gap in expectancy between HIV-positive and HIV-negative subjects.

An analysis of life expectancies at age 20 by race/ethnicity showed similar significant gains throughout the study period for whites, blacks, and Hispanics (P less than .0010), although HIV-positive whites and Hispanics did slightly but significantly better than blacks (P = .007 and .001, respectively),

There were also significant gains in life expectancy among men having sex with men, from 40 years in 1996 to 51 years in 2011, heterosexuals, from 38 years to 51 years, and among injectable drug users, from 36 to 46 years.

To see whether they could account for the 13-year gap that remained between HIV-positive and HIV-negative members, the authors looked at various care- and disease-related factors. When they considered those patients who received optimal therapy, with ART initiated when their CD4 counts were 500 or above, the expectancy gap narrowed to 7.9 years.

When they controlled for patients without hepatitis B or C infections, the gap narrowed to 7.2 years. HIV-positive patients with no drug or alcohol abuse had only 6.8 years less life expectancy than their HIV-negative counterparts, and those who did not smoke had only a 5.4 year life-expectancy decrement.

In the question-and-answer session following Dr. Marcus’ talk, an attendee suggested that some of the remaining gap may be explained by mental health differences between HIV-positive and HIV-negative patients.

“I would urge that you start looking at mental health issues and depression in particular, which is both vastly more common in people with HIV, and also has a demonstrable impact on mortality. That may explain some of the gap,” he said.

Dr. Marcus agreed about the importance of looking at this question, and noted that it is being actively explored in ongoing studies.

Dr. Marcus disclosed that she has been supported by a research grant to her institution from Merck.

BOSTON – Optimally treated patients with HIV are living longer than ever, and have narrowed but not completely closed the gap in life expectancy with their uninfected peers, investigators in a large cohort study reported.

In 1996, a 20-year-old infected with HIV could expect to live only 19 more years, to age 39. In 2011, the additional life expectancy for a 20-year-old HIV-positive subject was 53 years, meaning that given survival to age 20, he or she could expect to live to age 73, said Julia L. Marcus, Ph.D., from Kaiser Permanente Northern California in Oakland.

She and her colleagues studied life expectancy in a cohort of nearly 25,000 Kaiser Permanente California members who were HIV-positive and more than 250,000 HIV-negative members in an effort to better delineate differences in survival by HIV status than in earlier comparisons.

“This is the first study to our knowledge to directly compare life expectancy by HIV status, accounting for individual-level factors and access to health care. We have complete ascertainment of deaths, and therefore no loss to follow-up, and our results are generalizable to the broader insured population,” Dr. Marcus said at the Conference on Retroviruses and Opportunistic Infections.

The study results reflect the remarkable improvement in care of insured HIV-positive patients with the introduction of antiretroviral therapy (ART), which has allowed more than half of all HIV-positive individuals to live to age 50 or older, she said.

Previous studies suggesting that there is still a gap in life expectancy between HIV-positive and HIV-negative people had compared HIV-positive individuals with the general population, limiting their ability to account for differences in life expectancy by HIV status because of differences in sociodemographic factors, access to care, and risk factors that may affect survival, Dr. Marcus said.

To overcome these limitations, the investigators compared life expectancies for 24,768 HIV-positive people who were members of Kaiser Permanente California at any time from 1996 through 2011 with those of 257,600 HIV-negative members.

They conducted estimates by year of study follow-up, sex, race/ethnicity, HIV risk group, CD4 counts at ART initiation, and by key modifiable risk factors including viral hepatitis, drug and alcohol abuse, and smoking.

They found that over the course of the study, mortality rates among HIV-negative members remained relatively stable, at 439 per 100,000 person-years (py) in 1996, to 381/100,000 in 2011. In contrast, there was a steep decline among HIV-positive members, from 7,077/100,000 py in 1996, to 1,054/100,000 py in 2011.

Among women, remaining life expectancy at age 20 among those who were HIV-negative was 65 years in 1996, and 64 in 2011. In contrast, HIV-positive women saw an increase from 37 years in 1996 to 51 in 2011. Yet at the latest time point, there was still a 13-year gap in expectancy between HIV-negative and HIV-positive women.

Among HIV-negative men at age 20, additional life expectancy remained at 62 years throughout the study period, whereas among HIV-positive men it improved from 38 years in 1996 to 49 years in 2011. But here, too, there remained a 13-year gap in expectancy between HIV-positive and HIV-negative subjects.

An analysis of life expectancies at age 20 by race/ethnicity showed similar significant gains throughout the study period for whites, blacks, and Hispanics (P less than .0010), although HIV-positive whites and Hispanics did slightly but significantly better than blacks (P = .007 and .001, respectively),

There were also significant gains in life expectancy among men having sex with men, from 40 years in 1996 to 51 years in 2011, heterosexuals, from 38 years to 51 years, and among injectable drug users, from 36 to 46 years.

To see whether they could account for the 13-year gap that remained between HIV-positive and HIV-negative members, the authors looked at various care- and disease-related factors. When they considered those patients who received optimal therapy, with ART initiated when their CD4 counts were 500 or above, the expectancy gap narrowed to 7.9 years.

When they controlled for patients without hepatitis B or C infections, the gap narrowed to 7.2 years. HIV-positive patients with no drug or alcohol abuse had only 6.8 years less life expectancy than their HIV-negative counterparts, and those who did not smoke had only a 5.4 year life-expectancy decrement.

In the question-and-answer session following Dr. Marcus’ talk, an attendee suggested that some of the remaining gap may be explained by mental health differences between HIV-positive and HIV-negative patients.

“I would urge that you start looking at mental health issues and depression in particular, which is both vastly more common in people with HIV, and also has a demonstrable impact on mortality. That may explain some of the gap,” he said.

Dr. Marcus agreed about the importance of looking at this question, and noted that it is being actively explored in ongoing studies.

Dr. Marcus disclosed that she has been supported by a research grant to her institution from Merck.

BOSTON – Nearly 1 year after 11 new HIV infections were diagnosed in Scott County, Ind., a region that had an incidence of fewer than 1 HIV infection per year over the previous decade, 188 new HIV infections have now been diagnosed, and more than 90% of the cases were coinfected with hepatitis C (HCV), according to Dr. John T. Brooks of the Centers for Disease Control and Prevention.

Lessons from the outbreak, he said, include the inescapable fact that the United States is experiencing an expanding epidemic of heroin use that is driving an increase in injection drug use, putting many more U.S. residents at risk for the spread of HIV and HCV infection.

The response to the outbreak “required a large and extremely intensive collaboration of local, state, and federal public health resources in close partnership with community members, and like all outbreak investigations, there are two goals: First, establish the extent of the outbreak, and then institute prevention and control measures,” Dr. Brooks reported at a plenary session at the Conference on Retroviruses and Opportunistic Infections.

©PaulPaladin/thinkstockphotos.com

Once the cases were detected and confirmed, the health authorities went into action, deploying emergency command at the state level, similar to that deployed during a weather disaster, with a team of 35 disease intervention specialists and other public health workers from 14 states and the District of Columbia who went door to door, testing as many people as possible to find HIV infections, and tracing contacts to determine where additional, undiagnosed cases might be.

“The pattern of how we approached this outbreak is very much how you might approach tuberculosis, where you first detect that there’s a disease and confirm the diagnosis, you deploy an intervention to treat – sort of induction therapy – and once it’s under control you switch to consolidation therapy to keep the disease at bay, and then over time you might scan the person or follow up to see if the disease is recurring. The difference here is that we’re doing it on a population level,” said Dr. Brooks of the CDC’s division of HIV/AIDS prevention.

Astute observer spotted trend

The outbreak came to the attention of public health authorities when a “very, very astute” disease intervention specialist working in the county health department recognized that there were 11 new infections related to one another in Scott County, with the epicenter in the town of Austin.

Early in the outbreak, investigators determined that the HIV and HCV transmissions were occurring in a dense network of persons who inject drugs, mostly the opioid analgesic oxymorphone, but also heroin, methamphetamine, and cocaine. “During interviews, it was evident that 96% of the people had injected in the past 12 months, and that oxymorphone was the preferred drug used by 92%,” Dr. Brooks said.

Oxymorphone is available in generic and branded formulations. Although the brand name version (Opana and Opana ER) has a coating intended to prevent crushing the pills and dissolving the drug for the purpose of injection, “addiction can make you very creative, and the residents of this town had figured how to get around that,” Dr. Brooks said.

The outbreak was multigenerational, and it was not uncommon to find a household with three generations of drug abusers – grandparent, parents, and children – who injected drugs between 4 and 15 times each day, with one to as many as six needle-sharing partners per injection event, and sharing of injection equipment. Information was available on 181 of the 188 HIV-infected cases. The median age was 34 years (interquartile range, 28-42), 58% were male, 99% were non-Hispanic whites, and 96% had injected drugs within the past 12 months.

Jailhouse testing

The investigators established HIV testing both in the Scott County jail and in detention centers in surrounding counties in a sentinel system to determine whether the outbreak might have spread beyond the county line. The disease intervention specialists collected intravenous blood samples and performed point-of-care rapid testing for later confirmation, and for testing for acute HIV and HCV infection.

The workers also provided county residents with disease prevention educational materials and directed them to services as required, including treatment and antiretroviral therapy, and/or addition and harm reduction services and preexposure prophylaxis, if appropriate.

Major logistical challenges for responders included the fact that very few affected individuals were either employed or insured, and most lacked the necessary documents to enroll in state-supported care Medicaid expansion, recently adopted by Indiana as part of the Affordable Care Act.

In addition, residents in this impoverished, remote community in Southeastern Indiana – which ranks last among Indiana’s 92 counties in many health statistic categories – were aware of HIV or had correct information about transmission risks or treatment benefits.

Efforts were further hampered by the atmosphere of distrust between drug injectors and law enforcement; the lack of outpatient HIV or HCV care in the community; meager addiction services, including medication-assisted therapy; and a statewide ban on needle-exchange programs. In May of 2015, Indiana Gov. Mike Pence signed into law a bill allowing syringe exchange in areas where there was an urgent need because of disease outbreak.

In November of 2015, there was a retesting “blitz” in which disease intervention teams returned to the community and attempted to locate all persons who had previously tested negative, or had not been located on the first go-round and tested again to determine whether any of the residents had developed new infections.

“If there’s one message I’d like you to take away today,” Dr. Brooks told attendees, “it’s this: We all know now that this could happen again, but with your help and commitment, it doesn’t have to.”

BOSTON – Nearly 1 year after 11 new HIV infections were diagnosed in Scott County, Ind., a region that had an incidence of fewer than 1 HIV infection per year over the previous decade, 188 new HIV infections have now been diagnosed, and more than 90% of the cases were coinfected with hepatitis C (HCV), according to Dr. John T. Brooks of the Centers for Disease Control and Prevention.

Lessons from the outbreak, he said, include the inescapable fact that the United States is experiencing an expanding epidemic of heroin use that is driving an increase in injection drug use, putting many more U.S. residents at risk for the spread of HIV and HCV infection.

The response to the outbreak “required a large and extremely intensive collaboration of local, state, and federal public health resources in close partnership with community members, and like all outbreak investigations, there are two goals: First, establish the extent of the outbreak, and then institute prevention and control measures,” Dr. Brooks reported at a plenary session at the Conference on Retroviruses and Opportunistic Infections.

©PaulPaladin/thinkstockphotos.com

Once the cases were detected and confirmed, the health authorities went into action, deploying emergency command at the state level, similar to that deployed during a weather disaster, with a team of 35 disease intervention specialists and other public health workers from 14 states and the District of Columbia who went door to door, testing as many people as possible to find HIV infections, and tracing contacts to determine where additional, undiagnosed cases might be.

“The pattern of how we approached this outbreak is very much how you might approach tuberculosis, where you first detect that there’s a disease and confirm the diagnosis, you deploy an intervention to treat – sort of induction therapy – and once it’s under control you switch to consolidation therapy to keep the disease at bay, and then over time you might scan the person or follow up to see if the disease is recurring. The difference here is that we’re doing it on a population level,” said Dr. Brooks of the CDC’s division of HIV/AIDS prevention.

Astute observer spotted trend

The outbreak came to the attention of public health authorities when a “very, very astute” disease intervention specialist working in the county health department recognized that there were 11 new infections related to one another in Scott County, with the epicenter in the town of Austin.

Early in the outbreak, investigators determined that the HIV and HCV transmissions were occurring in a dense network of persons who inject drugs, mostly the opioid analgesic oxymorphone, but also heroin, methamphetamine, and cocaine. “During interviews, it was evident that 96% of the people had injected in the past 12 months, and that oxymorphone was the preferred drug used by 92%,” Dr. Brooks said.

Oxymorphone is available in generic and branded formulations. Although the brand name version (Opana and Opana ER) has a coating intended to prevent crushing the pills and dissolving the drug for the purpose of injection, “addiction can make you very creative, and the residents of this town had figured how to get around that,” Dr. Brooks said.

The outbreak was multigenerational, and it was not uncommon to find a household with three generations of drug abusers – grandparent, parents, and children – who injected drugs between 4 and 15 times each day, with one to as many as six needle-sharing partners per injection event, and sharing of injection equipment. Information was available on 181 of the 188 HIV-infected cases. The median age was 34 years (interquartile range, 28-42), 58% were male, 99% were non-Hispanic whites, and 96% had injected drugs within the past 12 months.

Jailhouse testing

The investigators established HIV testing both in the Scott County jail and in detention centers in surrounding counties in a sentinel system to determine whether the outbreak might have spread beyond the county line. The disease intervention specialists collected intravenous blood samples and performed point-of-care rapid testing for later confirmation, and for testing for acute HIV and HCV infection.

The workers also provided county residents with disease prevention educational materials and directed them to services as required, including treatment and antiretroviral therapy, and/or addition and harm reduction services and preexposure prophylaxis, if appropriate.

Major logistical challenges for responders included the fact that very few affected individuals were either employed or insured, and most lacked the necessary documents to enroll in state-supported care Medicaid expansion, recently adopted by Indiana as part of the Affordable Care Act.

In addition, residents in this impoverished, remote community in Southeastern Indiana – which ranks last among Indiana’s 92 counties in many health statistic categories – were aware of HIV or had correct information about transmission risks or treatment benefits.

Efforts were further hampered by the atmosphere of distrust between drug injectors and law enforcement; the lack of outpatient HIV or HCV care in the community; meager addiction services, including medication-assisted therapy; and a statewide ban on needle-exchange programs. In May of 2015, Indiana Gov. Mike Pence signed into law a bill allowing syringe exchange in areas where there was an urgent need because of disease outbreak.

In November of 2015, there was a retesting “blitz” in which disease intervention teams returned to the community and attempted to locate all persons who had previously tested negative, or had not been located on the first go-round and tested again to determine whether any of the residents had developed new infections.

“If there’s one message I’d like you to take away today,” Dr. Brooks told attendees, “it’s this: We all know now that this could happen again, but with your help and commitment, it doesn’t have to.”

BOSTON – Nearly 1 year after 11 new HIV infections were diagnosed in Scott County, Ind., a region that had an incidence of fewer than 1 HIV infection per year over the previous decade, 188 new HIV infections have now been diagnosed, and more than 90% of the cases were coinfected with hepatitis C (HCV), according to Dr. John T. Brooks of the Centers for Disease Control and Prevention.

Lessons from the outbreak, he said, include the inescapable fact that the United States is experiencing an expanding epidemic of heroin use that is driving an increase in injection drug use, putting many more U.S. residents at risk for the spread of HIV and HCV infection.

The response to the outbreak “required a large and extremely intensive collaboration of local, state, and federal public health resources in close partnership with community members, and like all outbreak investigations, there are two goals: First, establish the extent of the outbreak, and then institute prevention and control measures,” Dr. Brooks reported at a plenary session at the Conference on Retroviruses and Opportunistic Infections.

©PaulPaladin/thinkstockphotos.com

Once the cases were detected and confirmed, the health authorities went into action, deploying emergency command at the state level, similar to that deployed during a weather disaster, with a team of 35 disease intervention specialists and other public health workers from 14 states and the District of Columbia who went door to door, testing as many people as possible to find HIV infections, and tracing contacts to determine where additional, undiagnosed cases might be.

“The pattern of how we approached this outbreak is very much how you might approach tuberculosis, where you first detect that there’s a disease and confirm the diagnosis, you deploy an intervention to treat – sort of induction therapy – and once it’s under control you switch to consolidation therapy to keep the disease at bay, and then over time you might scan the person or follow up to see if the disease is recurring. The difference here is that we’re doing it on a population level,” said Dr. Brooks of the CDC’s division of HIV/AIDS prevention.

Astute observer spotted trend

The outbreak came to the attention of public health authorities when a “very, very astute” disease intervention specialist working in the county health department recognized that there were 11 new infections related to one another in Scott County, with the epicenter in the town of Austin.

Early in the outbreak, investigators determined that the HIV and HCV transmissions were occurring in a dense network of persons who inject drugs, mostly the opioid analgesic oxymorphone, but also heroin, methamphetamine, and cocaine. “During interviews, it was evident that 96% of the people had injected in the past 12 months, and that oxymorphone was the preferred drug used by 92%,” Dr. Brooks said.

Oxymorphone is available in generic and branded formulations. Although the brand name version (Opana and Opana ER) has a coating intended to prevent crushing the pills and dissolving the drug for the purpose of injection, “addiction can make you very creative, and the residents of this town had figured how to get around that,” Dr. Brooks said.

The outbreak was multigenerational, and it was not uncommon to find a household with three generations of drug abusers – grandparent, parents, and children – who injected drugs between 4 and 15 times each day, with one to as many as six needle-sharing partners per injection event, and sharing of injection equipment. Information was available on 181 of the 188 HIV-infected cases. The median age was 34 years (interquartile range, 28-42), 58% were male, 99% were non-Hispanic whites, and 96% had injected drugs within the past 12 months.

Jailhouse testing

The investigators established HIV testing both in the Scott County jail and in detention centers in surrounding counties in a sentinel system to determine whether the outbreak might have spread beyond the county line. The disease intervention specialists collected intravenous blood samples and performed point-of-care rapid testing for later confirmation, and for testing for acute HIV and HCV infection.

The workers also provided county residents with disease prevention educational materials and directed them to services as required, including treatment and antiretroviral therapy, and/or addition and harm reduction services and preexposure prophylaxis, if appropriate.

Major logistical challenges for responders included the fact that very few affected individuals were either employed or insured, and most lacked the necessary documents to enroll in state-supported care Medicaid expansion, recently adopted by Indiana as part of the Affordable Care Act.

In addition, residents in this impoverished, remote community in Southeastern Indiana – which ranks last among Indiana’s 92 counties in many health statistic categories – were aware of HIV or had correct information about transmission risks or treatment benefits.

Efforts were further hampered by the atmosphere of distrust between drug injectors and law enforcement; the lack of outpatient HIV or HCV care in the community; meager addiction services, including medication-assisted therapy; and a statewide ban on needle-exchange programs. In May of 2015, Indiana Gov. Mike Pence signed into law a bill allowing syringe exchange in areas where there was an urgent need because of disease outbreak.

In November of 2015, there was a retesting “blitz” in which disease intervention teams returned to the community and attempted to locate all persons who had previously tested negative, or had not been located on the first go-round and tested again to determine whether any of the residents had developed new infections.

“If there’s one message I’d like you to take away today,” Dr. Brooks told attendees, “it’s this: We all know now that this could happen again, but with your help and commitment, it doesn’t have to.”

BOSTON – There is a long history of the use of antibodies for prevention and treatment of many different infectious diseases, and now it’s HIV’s turn, a vaccine investigator said.

Data from animal models and early human trials suggest that recently isolated, broadly neutralizing monoclonal antibodies (mAbs) against HIV-1 may be effective for prevention of infection and for viral suppression in infected individuals, according to Dr. John R. Mascola from the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

©MattZ90/Thinkstock.com

“Antibodies are biologically active; even a single antibody can reduce plasma virus by 1-2 logs with a single infusion. However, selection for resistant strains can occur and does occur rapidly in the setting of incomplete viral suppression. So this strongly suggests the combination of antibodies, or antibodies plus antiretroviral drugs are likely to be required for viral suppression,” he said in a plenary talk at the Conference on Retroviruses and Opportunistic Infections.

The effect of antibodies on reduction or elimination of viral reservoirs, however, is still unclear, and will require additional research, he said.

There is a long history of passive immunization with antibodies, he said, beginning with “serum therapy” for diphtheria, tetanus, and streptococcal infections, and progressing to the use of immune globulins for the prevention of common viral diseases such as measles, poliomyelitis, cytomegalovirus, hepatitis A, and respiratory syncytial virus (in high-risk infants) and for postexposure prophylaxis of hepatitis B, rabies, and varicella-zoster virus, he said.

“In the infectious disease world, the concept of using antibodies for HIV has been around for a long time, really, based on our knowledge of all these other viral diseases. But what has changed and really invigorated the field is the discovery of many potent neutralizing antibodies since 2009,” he said.

More than 20 antibodies directed against several different viral binding sites have been described in the last 6 years alone.

Two important considerations for successful prevention of binding of HIV and entry into cells is the breadth (percentage of all HIV strains that are neutralized) and potency of mAbs, Dr. Mascola said.

More recently discovered mAbs are up to 500-fold more potent than older anti-HIV antibodies, the first of which were described in the early 1990s, but the perfect antibody with the right combination of breadth and potency has not been identified to date, he said.

Prevention

Preclinical studies conducted over the last 2 decades using ape and monkey models and simian HIV (SHIV) has shown that neutralizing antibodies can prevent infection, and that more recently discovered mAbs are especially effective when given before a viral challenge. However, there are few if any data on protection against viral challenge in humans, Dr. Mascola pointed out.

“What’s encouraging is that within the next couple of years, rather than where we are now where I can tell you about antibodies to only one site, there are very likely to be antibodies to four major sites on the virus,” he added.

Several phase I trials of an antibody labeled VRC01, directed against the CD4 binding site, are currently in the recruiting or planning stages.

Questions that remain about antibodies for HIV transmission prevention in humans included what level of mAbs is required for protections, where and how mAbs work (for example, in the lumen, epithelial surface, mucosal tissue, or lymphoid tissue), and whether Fc-mediated effector functions are required for protection.

Treatment

Whereas antibodies for prevention are aimed at blocking transmission and acquisition of infection, antibodies for treatment of HIV have a different clinical use, as complements to antiretroviral therapy, with a different mechanism of action. Therapeutic antibodies have the potential to eliminate infected cells, and could help to deplete cell-associated viral reservoirs, Dr. Mascola said.

During acute infection, they could be used in tandem with antiretroviral therapy for quick reduction of viremia and to limit seeding of a viral reservoir. Some long-lasting antibodies could help with maintenance of viral suppression.

As noted before, antibodies directed against HIV-1 are biologically active and can markedly reduce plasma viremia, but are subject to rapid development of resistance in the setting of incomplete viral suppression. Thus, mAbs will likely be used in combination with other mAbs or antiretroviral drugs to achieve effective viral suppression, and antibodies with long half-lives will likely be needed to achieve depletion of viral reservoirs, Dr. Mascola said.

Dr. Mascola is an employee of the National Institutes of Health. He reported no other conflicts.

BOSTON – There is a long history of the use of antibodies for prevention and treatment of many different infectious diseases, and now it’s HIV’s turn, a vaccine investigator said.

Data from animal models and early human trials suggest that recently isolated, broadly neutralizing monoclonal antibodies (mAbs) against HIV-1 may be effective for prevention of infection and for viral suppression in infected individuals, according to Dr. John R. Mascola from the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

©MattZ90/Thinkstock.com

“Antibodies are biologically active; even a single antibody can reduce plasma virus by 1-2 logs with a single infusion. However, selection for resistant strains can occur and does occur rapidly in the setting of incomplete viral suppression. So this strongly suggests the combination of antibodies, or antibodies plus antiretroviral drugs are likely to be required for viral suppression,” he said in a plenary talk at the Conference on Retroviruses and Opportunistic Infections.

The effect of antibodies on reduction or elimination of viral reservoirs, however, is still unclear, and will require additional research, he said.

There is a long history of passive immunization with antibodies, he said, beginning with “serum therapy” for diphtheria, tetanus, and streptococcal infections, and progressing to the use of immune globulins for the prevention of common viral diseases such as measles, poliomyelitis, cytomegalovirus, hepatitis A, and respiratory syncytial virus (in high-risk infants) and for postexposure prophylaxis of hepatitis B, rabies, and varicella-zoster virus, he said.

“In the infectious disease world, the concept of using antibodies for HIV has been around for a long time, really, based on our knowledge of all these other viral diseases. But what has changed and really invigorated the field is the discovery of many potent neutralizing antibodies since 2009,” he said.

More than 20 antibodies directed against several different viral binding sites have been described in the last 6 years alone.

Two important considerations for successful prevention of binding of HIV and entry into cells is the breadth (percentage of all HIV strains that are neutralized) and potency of mAbs, Dr. Mascola said.

More recently discovered mAbs are up to 500-fold more potent than older anti-HIV antibodies, the first of which were described in the early 1990s, but the perfect antibody with the right combination of breadth and potency has not been identified to date, he said.

Prevention

Preclinical studies conducted over the last 2 decades using ape and monkey models and simian HIV (SHIV) has shown that neutralizing antibodies can prevent infection, and that more recently discovered mAbs are especially effective when given before a viral challenge. However, there are few if any data on protection against viral challenge in humans, Dr. Mascola pointed out.

“What’s encouraging is that within the next couple of years, rather than where we are now where I can tell you about antibodies to only one site, there are very likely to be antibodies to four major sites on the virus,” he added.

Several phase I trials of an antibody labeled VRC01, directed against the CD4 binding site, are currently in the recruiting or planning stages.

Questions that remain about antibodies for HIV transmission prevention in humans included what level of mAbs is required for protections, where and how mAbs work (for example, in the lumen, epithelial surface, mucosal tissue, or lymphoid tissue), and whether Fc-mediated effector functions are required for protection.

Treatment

Whereas antibodies for prevention are aimed at blocking transmission and acquisition of infection, antibodies for treatment of HIV have a different clinical use, as complements to antiretroviral therapy, with a different mechanism of action. Therapeutic antibodies have the potential to eliminate infected cells, and could help to deplete cell-associated viral reservoirs, Dr. Mascola said.

During acute infection, they could be used in tandem with antiretroviral therapy for quick reduction of viremia and to limit seeding of a viral reservoir. Some long-lasting antibodies could help with maintenance of viral suppression.

As noted before, antibodies directed against HIV-1 are biologically active and can markedly reduce plasma viremia, but are subject to rapid development of resistance in the setting of incomplete viral suppression. Thus, mAbs will likely be used in combination with other mAbs or antiretroviral drugs to achieve effective viral suppression, and antibodies with long half-lives will likely be needed to achieve depletion of viral reservoirs, Dr. Mascola said.

Dr. Mascola is an employee of the National Institutes of Health. He reported no other conflicts.

BOSTON – There is a long history of the use of antibodies for prevention and treatment of many different infectious diseases, and now it’s HIV’s turn, a vaccine investigator said.

Data from animal models and early human trials suggest that recently isolated, broadly neutralizing monoclonal antibodies (mAbs) against HIV-1 may be effective for prevention of infection and for viral suppression in infected individuals, according to Dr. John R. Mascola from the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

©MattZ90/Thinkstock.com

“Antibodies are biologically active; even a single antibody can reduce plasma virus by 1-2 logs with a single infusion. However, selection for resistant strains can occur and does occur rapidly in the setting of incomplete viral suppression. So this strongly suggests the combination of antibodies, or antibodies plus antiretroviral drugs are likely to be required for viral suppression,” he said in a plenary talk at the Conference on Retroviruses and Opportunistic Infections.

The effect of antibodies on reduction or elimination of viral reservoirs, however, is still unclear, and will require additional research, he said.

There is a long history of passive immunization with antibodies, he said, beginning with “serum therapy” for diphtheria, tetanus, and streptococcal infections, and progressing to the use of immune globulins for the prevention of common viral diseases such as measles, poliomyelitis, cytomegalovirus, hepatitis A, and respiratory syncytial virus (in high-risk infants) and for postexposure prophylaxis of hepatitis B, rabies, and varicella-zoster virus, he said.

“In the infectious disease world, the concept of using antibodies for HIV has been around for a long time, really, based on our knowledge of all these other viral diseases. But what has changed and really invigorated the field is the discovery of many potent neutralizing antibodies since 2009,” he said.

More than 20 antibodies directed against several different viral binding sites have been described in the last 6 years alone.

Two important considerations for successful prevention of binding of HIV and entry into cells is the breadth (percentage of all HIV strains that are neutralized) and potency of mAbs, Dr. Mascola said.

More recently discovered mAbs are up to 500-fold more potent than older anti-HIV antibodies, the first of which were described in the early 1990s, but the perfect antibody with the right combination of breadth and potency has not been identified to date, he said.

Prevention

Preclinical studies conducted over the last 2 decades using ape and monkey models and simian HIV (SHIV) has shown that neutralizing antibodies can prevent infection, and that more recently discovered mAbs are especially effective when given before a viral challenge. However, there are few if any data on protection against viral challenge in humans, Dr. Mascola pointed out.

“What’s encouraging is that within the next couple of years, rather than where we are now where I can tell you about antibodies to only one site, there are very likely to be antibodies to four major sites on the virus,” he added.

Several phase I trials of an antibody labeled VRC01, directed against the CD4 binding site, are currently in the recruiting or planning stages.

Questions that remain about antibodies for HIV transmission prevention in humans included what level of mAbs is required for protections, where and how mAbs work (for example, in the lumen, epithelial surface, mucosal tissue, or lymphoid tissue), and whether Fc-mediated effector functions are required for protection.

Treatment

Whereas antibodies for prevention are aimed at blocking transmission and acquisition of infection, antibodies for treatment of HIV have a different clinical use, as complements to antiretroviral therapy, with a different mechanism of action. Therapeutic antibodies have the potential to eliminate infected cells, and could help to deplete cell-associated viral reservoirs, Dr. Mascola said.

During acute infection, they could be used in tandem with antiretroviral therapy for quick reduction of viremia and to limit seeding of a viral reservoir. Some long-lasting antibodies could help with maintenance of viral suppression.

As noted before, antibodies directed against HIV-1 are biologically active and can markedly reduce plasma viremia, but are subject to rapid development of resistance in the setting of incomplete viral suppression. Thus, mAbs will likely be used in combination with other mAbs or antiretroviral drugs to achieve effective viral suppression, and antibodies with long half-lives will likely be needed to achieve depletion of viral reservoirs, Dr. Mascola said.

Dr. Mascola is an employee of the National Institutes of Health. He reported no other conflicts.

BOSTON – People with HIV who get proper medical care stand a better chance than ever of achieving durable viral suppression, said investigators from the Centers for Disease Control and Prevention at the Conference on Retroviruses and Opportunistic Infections.

Data from a nationwide surveillance sample of patients receiving medical care for HIV in the United States shows that the proportion of all HIV-infected persons whose viral levels were suppressed below 200 copies/mL at their most recent visit increased from 72% in 2009 to 80% in 2013 (P for trend less than .01), reported Heather Bradley, Ph.D., of the CDC.

“These findings are really encouraging in terms of progress toward the National HIV/AIDS strategy goals of both improving the health of persons living with HIV and reducing infections,” she said at a media briefing following her presentation of data at in a CROI 2016 oral session.

The CDC investigators drew on the Medical Monitoring Project, a surveillance system that provides nationally representative data on HIV medical care to estimate the proportion of persons receiving care who achieve viral suppression at both their last tests and at all tests during the previous 12 months.

They collected data on a total of 23,125 HIV-infected persons from interviews and medical records, and looked at trends over time in viral suppression in the population as a whole and by categories of sex, age, race/ethnicity, sexual behavior, and sexual orientation.

“Encouragingly, the largest increases that we observed were seen among populations with the lowest level of viral suppression in 2009, including young people and non-Hispanic blacks,” Dr. Bradley said.

Among 18- to 29-year-olds, suppression rates improved from 56% in 2009 to 68% in 2013 (P for trend less than .001), and among non-Hispanic blacks the rates improved from 64% to 76%, respectively (P for trend less than .01).

The trend toward improved viral suppression was in fact seen in both men and in women, among all age groups, in non-Hispanic whites and Hispanics, and in men who have sex with men; men who have sex with women; and women who have sex with men.

In addition, there was significant improvement in the proportion of persons with viral suppression at all tests during the previous year, with rates growing from 58% in 2009 to 68% in 2013.

Dr. Bradley said that the improvement in viral control may be attributable to public health efforts to improve access to medical care for persons with HIV, and to promotion of early initiation of antiretroviral therapies.

The study was funded by the CDC. Dr. Bradley is a CDC employee.

BOSTON – People with HIV who get proper medical care stand a better chance than ever of achieving durable viral suppression, said investigators from the Centers for Disease Control and Prevention at the Conference on Retroviruses and Opportunistic Infections.

Data from a nationwide surveillance sample of patients receiving medical care for HIV in the United States shows that the proportion of all HIV-infected persons whose viral levels were suppressed below 200 copies/mL at their most recent visit increased from 72% in 2009 to 80% in 2013 (P for trend less than .01), reported Heather Bradley, Ph.D., of the CDC.

“These findings are really encouraging in terms of progress toward the National HIV/AIDS strategy goals of both improving the health of persons living with HIV and reducing infections,” she said at a media briefing following her presentation of data at in a CROI 2016 oral session.

The CDC investigators drew on the Medical Monitoring Project, a surveillance system that provides nationally representative data on HIV medical care to estimate the proportion of persons receiving care who achieve viral suppression at both their last tests and at all tests during the previous 12 months.

They collected data on a total of 23,125 HIV-infected persons from interviews and medical records, and looked at trends over time in viral suppression in the population as a whole and by categories of sex, age, race/ethnicity, sexual behavior, and sexual orientation.

“Encouragingly, the largest increases that we observed were seen among populations with the lowest level of viral suppression in 2009, including young people and non-Hispanic blacks,” Dr. Bradley said.

Among 18- to 29-year-olds, suppression rates improved from 56% in 2009 to 68% in 2013 (P for trend less than .001), and among non-Hispanic blacks the rates improved from 64% to 76%, respectively (P for trend less than .01).

The trend toward improved viral suppression was in fact seen in both men and in women, among all age groups, in non-Hispanic whites and Hispanics, and in men who have sex with men; men who have sex with women; and women who have sex with men.

In addition, there was significant improvement in the proportion of persons with viral suppression at all tests during the previous year, with rates growing from 58% in 2009 to 68% in 2013.

Dr. Bradley said that the improvement in viral control may be attributable to public health efforts to improve access to medical care for persons with HIV, and to promotion of early initiation of antiretroviral therapies.

The study was funded by the CDC. Dr. Bradley is a CDC employee.

BOSTON – People with HIV who get proper medical care stand a better chance than ever of achieving durable viral suppression, said investigators from the Centers for Disease Control and Prevention at the Conference on Retroviruses and Opportunistic Infections.

Data from a nationwide surveillance sample of patients receiving medical care for HIV in the United States shows that the proportion of all HIV-infected persons whose viral levels were suppressed below 200 copies/mL at their most recent visit increased from 72% in 2009 to 80% in 2013 (P for trend less than .01), reported Heather Bradley, Ph.D., of the CDC.

“These findings are really encouraging in terms of progress toward the National HIV/AIDS strategy goals of both improving the health of persons living with HIV and reducing infections,” she said at a media briefing following her presentation of data at in a CROI 2016 oral session.

The CDC investigators drew on the Medical Monitoring Project, a surveillance system that provides nationally representative data on HIV medical care to estimate the proportion of persons receiving care who achieve viral suppression at both their last tests and at all tests during the previous 12 months.

They collected data on a total of 23,125 HIV-infected persons from interviews and medical records, and looked at trends over time in viral suppression in the population as a whole and by categories of sex, age, race/ethnicity, sexual behavior, and sexual orientation.

“Encouragingly, the largest increases that we observed were seen among populations with the lowest level of viral suppression in 2009, including young people and non-Hispanic blacks,” Dr. Bradley said.

Among 18- to 29-year-olds, suppression rates improved from 56% in 2009 to 68% in 2013 (P for trend less than .001), and among non-Hispanic blacks the rates improved from 64% to 76%, respectively (P for trend less than .01).

The trend toward improved viral suppression was in fact seen in both men and in women, among all age groups, in non-Hispanic whites and Hispanics, and in men who have sex with men; men who have sex with women; and women who have sex with men.

In addition, there was significant improvement in the proportion of persons with viral suppression at all tests during the previous year, with rates growing from 58% in 2009 to 68% in 2013.

Dr. Bradley said that the improvement in viral control may be attributable to public health efforts to improve access to medical care for persons with HIV, and to promotion of early initiation of antiretroviral therapies.

The study was funded by the CDC. Dr. Bradley is a CDC employee.

BOSTON – Although antiretroviral therapy (ART) has been shown to reduce risk of HIV transmission, particularly among heterosexuals, there is a gap between patient perception of infectiousness and actual risk of HIV transmission, suggesting that clinicians need to do better at discussing implications with patients on treatment.

Among patients participating in a randomized clinical trial comparing three ART regimens, nearly half reported a decline in their perception of their own infectiousness (POI) at 48 weeks compared with study entry, but few participants thought themselves to be noninfectious at any time point, reported Dr. Raphael Landovitz of the David Geffen School of Medicine at the University of California, Los Angeles.

“We think this highlights some important opportunities for finding populations who need more education about what it means for their sexual partners in terms of their infectiousness by a sexual route as they achieve therapy, and I think as providers we can do a better job about contextualizing the benefits of antiretroviral therapy, not only for individuals, but for populations,” he said at a media briefing following his presentation of the data in an oral abstract session at the Conference on Retroviruses and Opportunistic Infections.

Dr. Landovitz and colleagues conducted a secondary analysis of data from the AIDS Clinical Trials Group (ACTG) A5257 Trial, which compared tenofovir/emtricitabine in combination with either atazanavir, raltegravir, or darunavir.

Patients in the trial were asked at baseline and every 48 weeks to rate on a visual analog scale from 0 to 100 their response to the question, “How likely would you be to give someone HIV if you had unprotected sex with them today?” – with 0 being not at all infectious, and 100 being highly infectious.

At baseline, 6% had a POI of not at all infectious, 10% thought themselves to be at low risk for HIV transmission. 26% considered themselves at medium risk, and 58% had a POI of highly infectious.

At week 48, 10% rated themselves as not infectious, 32% as low risk, 20% as medium risk, and 38% as highly at risk of transmission from unprotected sex.

These POI scores were at odds with the actual risk of infectiousness, however: At week 48, 91% of participants had HIV RNA levels of less than 50 copies per mL, the investigators found.

In multivariate analysis controlling for sociodemographic factors, sexual partner preferences and any stimulant drug use, factors associated with a greater probability of decline in POI included higher baseline POI, younger age, and higher level of education. In contrast, non-Hispanic blacks and patients with CD4 levels lower than 50 cells at the start of ART were less likely to have a decline in POI.

In all, 99 patients had a decline to a POI of not infectious. Factors associated with this change were baseline POI, female sex, and no stimulant drug use. Of those who thought of themselves as not infectious at week 48, 8 had HIV RNA levels about 50 copies/mL.

Interestingly, actual viral suppression was not associated with POI, Dr. Landovitz said.

In the briefing, he said that it’s incumbent on caregivers not to present patients with either/or choices, but instead to have a nuanced discussion about relative transmission risks. For example, if the patient has undetectable viral levels and is on treatment, is tested and treated for other sexually transmitted infections and has a known sexual dynamic, he or she probably has a very low risk of transmitting HIV to his/her sexual partner, he said.

However, “the challenge lies in messaging to patients that there are a lot of assumptions in that statement. What if the HIV-infected person has not been consistent with [his or her] antiretroviral therapy for whatever reason? ... What if there’s been something traumatic going on in their lives, or what if there has been a new substance abuse overlay that’s compromised their ability to adhere, and they’re no longer virologically suppressed as they thought they were at their last measurement? Then that’s not a guarantee [of low risk],” he said.

“I try and couch it to patients that based on what we know, if someone really is on treatment and undetectable, the risk of sexual transmission is very low. It’s probably not zero, but it’s very, very low,” he added.

Primary funding for ACGT A5257 came from the National Institute of Allergy and Infectious Diseases. Dr. Landovitz disclosed receiving research grants to his institution and consulting fees from Gilead Sciences.

BOSTON – Although antiretroviral therapy (ART) has been shown to reduce risk of HIV transmission, particularly among heterosexuals, there is a gap between patient perception of infectiousness and actual risk of HIV transmission, suggesting that clinicians need to do better at discussing implications with patients on treatment.

Among patients participating in a randomized clinical trial comparing three ART regimens, nearly half reported a decline in their perception of their own infectiousness (POI) at 48 weeks compared with study entry, but few participants thought themselves to be noninfectious at any time point, reported Dr. Raphael Landovitz of the David Geffen School of Medicine at the University of California, Los Angeles.

“We think this highlights some important opportunities for finding populations who need more education about what it means for their sexual partners in terms of their infectiousness by a sexual route as they achieve therapy, and I think as providers we can do a better job about contextualizing the benefits of antiretroviral therapy, not only for individuals, but for populations,” he said at a media briefing following his presentation of the data in an oral abstract session at the Conference on Retroviruses and Opportunistic Infections.

Dr. Landovitz and colleagues conducted a secondary analysis of data from the AIDS Clinical Trials Group (ACTG) A5257 Trial, which compared tenofovir/emtricitabine in combination with either atazanavir, raltegravir, or darunavir.

Patients in the trial were asked at baseline and every 48 weeks to rate on a visual analog scale from 0 to 100 their response to the question, “How likely would you be to give someone HIV if you had unprotected sex with them today?” – with 0 being not at all infectious, and 100 being highly infectious.

At baseline, 6% had a POI of not at all infectious, 10% thought themselves to be at low risk for HIV transmission. 26% considered themselves at medium risk, and 58% had a POI of highly infectious.

At week 48, 10% rated themselves as not infectious, 32% as low risk, 20% as medium risk, and 38% as highly at risk of transmission from unprotected sex.

These POI scores were at odds with the actual risk of infectiousness, however: At week 48, 91% of participants had HIV RNA levels of less than 50 copies per mL, the investigators found.

In multivariate analysis controlling for sociodemographic factors, sexual partner preferences and any stimulant drug use, factors associated with a greater probability of decline in POI included higher baseline POI, younger age, and higher level of education. In contrast, non-Hispanic blacks and patients with CD4 levels lower than 50 cells at the start of ART were less likely to have a decline in POI.

In all, 99 patients had a decline to a POI of not infectious. Factors associated with this change were baseline POI, female sex, and no stimulant drug use. Of those who thought of themselves as not infectious at week 48, 8 had HIV RNA levels about 50 copies/mL.

Interestingly, actual viral suppression was not associated with POI, Dr. Landovitz said.

In the briefing, he said that it’s incumbent on caregivers not to present patients with either/or choices, but instead to have a nuanced discussion about relative transmission risks. For example, if the patient has undetectable viral levels and is on treatment, is tested and treated for other sexually transmitted infections and has a known sexual dynamic, he or she probably has a very low risk of transmitting HIV to his/her sexual partner, he said.

However, “the challenge lies in messaging to patients that there are a lot of assumptions in that statement. What if the HIV-infected person has not been consistent with [his or her] antiretroviral therapy for whatever reason? ... What if there’s been something traumatic going on in their lives, or what if there has been a new substance abuse overlay that’s compromised their ability to adhere, and they’re no longer virologically suppressed as they thought they were at their last measurement? Then that’s not a guarantee [of low risk],” he said.

“I try and couch it to patients that based on what we know, if someone really is on treatment and undetectable, the risk of sexual transmission is very low. It’s probably not zero, but it’s very, very low,” he added.

Primary funding for ACGT A5257 came from the National Institute of Allergy and Infectious Diseases. Dr. Landovitz disclosed receiving research grants to his institution and consulting fees from Gilead Sciences.

BOSTON – Although antiretroviral therapy (ART) has been shown to reduce risk of HIV transmission, particularly among heterosexuals, there is a gap between patient perception of infectiousness and actual risk of HIV transmission, suggesting that clinicians need to do better at discussing implications with patients on treatment.

Among patients participating in a randomized clinical trial comparing three ART regimens, nearly half reported a decline in their perception of their own infectiousness (POI) at 48 weeks compared with study entry, but few participants thought themselves to be noninfectious at any time point, reported Dr. Raphael Landovitz of the David Geffen School of Medicine at the University of California, Los Angeles.

“We think this highlights some important opportunities for finding populations who need more education about what it means for their sexual partners in terms of their infectiousness by a sexual route as they achieve therapy, and I think as providers we can do a better job about contextualizing the benefits of antiretroviral therapy, not only for individuals, but for populations,” he said at a media briefing following his presentation of the data in an oral abstract session at the Conference on Retroviruses and Opportunistic Infections.

Dr. Landovitz and colleagues conducted a secondary analysis of data from the AIDS Clinical Trials Group (ACTG) A5257 Trial, which compared tenofovir/emtricitabine in combination with either atazanavir, raltegravir, or darunavir.

Patients in the trial were asked at baseline and every 48 weeks to rate on a visual analog scale from 0 to 100 their response to the question, “How likely would you be to give someone HIV if you had unprotected sex with them today?” – with 0 being not at all infectious, and 100 being highly infectious.

At baseline, 6% had a POI of not at all infectious, 10% thought themselves to be at low risk for HIV transmission. 26% considered themselves at medium risk, and 58% had a POI of highly infectious.

At week 48, 10% rated themselves as not infectious, 32% as low risk, 20% as medium risk, and 38% as highly at risk of transmission from unprotected sex.

These POI scores were at odds with the actual risk of infectiousness, however: At week 48, 91% of participants had HIV RNA levels of less than 50 copies per mL, the investigators found.

In multivariate analysis controlling for sociodemographic factors, sexual partner preferences and any stimulant drug use, factors associated with a greater probability of decline in POI included higher baseline POI, younger age, and higher level of education. In contrast, non-Hispanic blacks and patients with CD4 levels lower than 50 cells at the start of ART were less likely to have a decline in POI.

In all, 99 patients had a decline to a POI of not infectious. Factors associated with this change were baseline POI, female sex, and no stimulant drug use. Of those who thought of themselves as not infectious at week 48, 8 had HIV RNA levels about 50 copies/mL.

Interestingly, actual viral suppression was not associated with POI, Dr. Landovitz said.

In the briefing, he said that it’s incumbent on caregivers not to present patients with either/or choices, but instead to have a nuanced discussion about relative transmission risks. For example, if the patient has undetectable viral levels and is on treatment, is tested and treated for other sexually transmitted infections and has a known sexual dynamic, he or she probably has a very low risk of transmitting HIV to his/her sexual partner, he said.

However, “the challenge lies in messaging to patients that there are a lot of assumptions in that statement. What if the HIV-infected person has not been consistent with [his or her] antiretroviral therapy for whatever reason? ... What if there’s been something traumatic going on in their lives, or what if there has been a new substance abuse overlay that’s compromised their ability to adhere, and they’re no longer virologically suppressed as they thought they were at their last measurement? Then that’s not a guarantee [of low risk],” he said.

“I try and couch it to patients that based on what we know, if someone really is on treatment and undetectable, the risk of sexual transmission is very low. It’s probably not zero, but it’s very, very low,” he added.

Primary funding for ACGT A5257 came from the National Institute of Allergy and Infectious Diseases. Dr. Landovitz disclosed receiving research grants to his institution and consulting fees from Gilead Sciences.

BOSTON – Switching HIV-infected South African children from ritonavir-boosted lopinavir (LPV/r) to efavirenz (EFV)-based antiretroviral therapy improved bone mineral content in the children, compared with remaining on LPV/r, according to a study presented at the Conference on Retroviruses and Opportunistic Infections.

HIV infection affects bone accrual but there are limited data on how to optimize antiretrovirals to improve bone outcomes in HIV-infected children, said Dr. Stephen Arpadi, professor of pediatrics at Columbia University (N.Y.) Medical Center, and lead author of the study. To determine whether a preemptive switch from LPV/r to EFV antiretroviral therapy might be associated with beneficial outcomes in terms of children’s bone development, his team reviewed the results of a randomized clinical trial of HIV-infected children undertaken in Johannesburg, South Africa.

Columbia University Medical Center

Two hundred twenty HIV-infected children aged 5-10 years (mean 6.4 years) were enrolled 1-4 years (mean 2.1 years) after randomization in the trial, while 180 similarly-aged HIV-uninfected children were recruited at the same site in Johannesburg for comparison. Among HIV-infected children, 110 were on EFV and 110 LPV/r at the time of assessment. All children also were on two nucleoside reverse transcriptase inhibitors, including 3TC (lamivudine) and ABC (abacavir), AZT, or d4T (stavudine). None were on TDF (tenofovir).

The investigators – part of the CHANGES Bone Study Team – assessed the children’s bone mineral content (BMC), fat mass, and lean body mass of the whole body by Dual-energy X-ray absorptiometry. Sex-specific BMC-for-height Z-scores for the infected children were generated using the BMC-for-height distribution of the uninfected controls. The children with HIV currently receiving EFV were compared with those on LPV/r.

Dr. Arpadi told CROI attendees that the BMC Z score was –0.49 in the EFV group and –1.07 in the LPV/r group, and that this association remained significant (P less than .001) and of a similar magnitude (Z-score difference, 0.58) after adjustment for age, fat mass, lean mass, vigorous physical activity, dietary vitamin D and calcium, CD4, and viral load. Sex-stratified analysis showed similar size effects in both boys and girls.

Higher fat and lean body mass also were independently associated with better bone mass outcomes in the children, Dr. Arpadi affirmed. “The use of bone friendly drugs may be beneficial for bone health in children with HIV,” he concluded.

The study was supported by the National Institutes of Health. Dr. Arpadi reported no conflicts of interest.

[email protected]

On Twitter @richpizzi

BOSTON – Switching HIV-infected South African children from ritonavir-boosted lopinavir (LPV/r) to efavirenz (EFV)-based antiretroviral therapy improved bone mineral content in the children, compared with remaining on LPV/r, according to a study presented at the Conference on Retroviruses and Opportunistic Infections.

HIV infection affects bone accrual but there are limited data on how to optimize antiretrovirals to improve bone outcomes in HIV-infected children, said Dr. Stephen Arpadi, professor of pediatrics at Columbia University (N.Y.) Medical Center, and lead author of the study. To determine whether a preemptive switch from LPV/r to EFV antiretroviral therapy might be associated with beneficial outcomes in terms of children’s bone development, his team reviewed the results of a randomized clinical trial of HIV-infected children undertaken in Johannesburg, South Africa.

Columbia University Medical Center

Two hundred twenty HIV-infected children aged 5-10 years (mean 6.4 years) were enrolled 1-4 years (mean 2.1 years) after randomization in the trial, while 180 similarly-aged HIV-uninfected children were recruited at the same site in Johannesburg for comparison. Among HIV-infected children, 110 were on EFV and 110 LPV/r at the time of assessment. All children also were on two nucleoside reverse transcriptase inhibitors, including 3TC (lamivudine) and ABC (abacavir), AZT, or d4T (stavudine). None were on TDF (tenofovir).

The investigators – part of the CHANGES Bone Study Team – assessed the children’s bone mineral content (BMC), fat mass, and lean body mass of the whole body by Dual-energy X-ray absorptiometry. Sex-specific BMC-for-height Z-scores for the infected children were generated using the BMC-for-height distribution of the uninfected controls. The children with HIV currently receiving EFV were compared with those on LPV/r.

Dr. Arpadi told CROI attendees that the BMC Z score was –0.49 in the EFV group and –1.07 in the LPV/r group, and that this association remained significant (P less than .001) and of a similar magnitude (Z-score difference, 0.58) after adjustment for age, fat mass, lean mass, vigorous physical activity, dietary vitamin D and calcium, CD4, and viral load. Sex-stratified analysis showed similar size effects in both boys and girls.

Higher fat and lean body mass also were independently associated with better bone mass outcomes in the children, Dr. Arpadi affirmed. “The use of bone friendly drugs may be beneficial for bone health in children with HIV,” he concluded.

The study was supported by the National Institutes of Health. Dr. Arpadi reported no conflicts of interest.

[email protected]

On Twitter @richpizzi

BOSTON – Switching HIV-infected South African children from ritonavir-boosted lopinavir (LPV/r) to efavirenz (EFV)-based antiretroviral therapy improved bone mineral content in the children, compared with remaining on LPV/r, according to a study presented at the Conference on Retroviruses and Opportunistic Infections.

HIV infection affects bone accrual but there are limited data on how to optimize antiretrovirals to improve bone outcomes in HIV-infected children, said Dr. Stephen Arpadi, professor of pediatrics at Columbia University (N.Y.) Medical Center, and lead author of the study. To determine whether a preemptive switch from LPV/r to EFV antiretroviral therapy might be associated with beneficial outcomes in terms of children’s bone development, his team reviewed the results of a randomized clinical trial of HIV-infected children undertaken in Johannesburg, South Africa.

Columbia University Medical Center

Two hundred twenty HIV-infected children aged 5-10 years (mean 6.4 years) were enrolled 1-4 years (mean 2.1 years) after randomization in the trial, while 180 similarly-aged HIV-uninfected children were recruited at the same site in Johannesburg for comparison. Among HIV-infected children, 110 were on EFV and 110 LPV/r at the time of assessment. All children also were on two nucleoside reverse transcriptase inhibitors, including 3TC (lamivudine) and ABC (abacavir), AZT, or d4T (stavudine). None were on TDF (tenofovir).

The investigators – part of the CHANGES Bone Study Team – assessed the children’s bone mineral content (BMC), fat mass, and lean body mass of the whole body by Dual-energy X-ray absorptiometry. Sex-specific BMC-for-height Z-scores for the infected children were generated using the BMC-for-height distribution of the uninfected controls. The children with HIV currently receiving EFV were compared with those on LPV/r.

Dr. Arpadi told CROI attendees that the BMC Z score was –0.49 in the EFV group and –1.07 in the LPV/r group, and that this association remained significant (P less than .001) and of a similar magnitude (Z-score difference, 0.58) after adjustment for age, fat mass, lean mass, vigorous physical activity, dietary vitamin D and calcium, CD4, and viral load. Sex-stratified analysis showed similar size effects in both boys and girls.

Higher fat and lean body mass also were independently associated with better bone mass outcomes in the children, Dr. Arpadi affirmed. “The use of bone friendly drugs may be beneficial for bone health in children with HIV,” he concluded.

The study was supported by the National Institutes of Health. Dr. Arpadi reported no conflicts of interest.

[email protected]

On Twitter @richpizzi

BOSTON – A majority of Ebola virus survivors continue to have significant physical, psychological, and sociological consequences for an extended period after discharge, investigators report.

Among 417 Ebola virus survivors enrolled in a follow-up study in Guinea, about 80% had residual clinical signs up to 9 months after discharge, reported Dr. Eric Delaporte of the French National Institute of Health and Medical Research (INSERM) and Montpellier (France) University.

Results of a second, small study, also from Guinea, suggest that up to 10% of men infected with Ebola have semen that remains positive for the virus for nearly a year after disease onset, said Dr. Daouda Sissoko of INSERM in Bordeaux, France.

“The results describe a post-Ebola syndrome with frequent clinical symptoms long after discharge, the gravity of ocular complications, long-term RNA positivity in semen, and the frequency of psychological consequences of the disease,” Dr. Delaporte said at a media briefing prior to presentation of the data in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

Dr. Delaporte is a coinvestigator in the Postebogui Cohort Study looking at Ebola survivors in Conakry and Macenta, Guinea. The goals of the study are to provide follow-up care for survivors and to describe the clinical, biologic, virologic, immunologic, and psychosocial consequences of infection with Ebola virus.

At CROI 2016, investigators reported on the first 417 patients enrolled, including 60 children. The median age was 28 years.

The investigators found that 46% of patients reported joint pains or other rheumatologic signs, 32% had neuropsychiatric signs, 29% reported chronic headache, 22% reported fatigue, and 16% had ophthalmologic signs,

Ophthalmic slit-lamp examinations in 160 patients showed 24 cases of uveitis, 4 cases of episcleritis, 2 cases of keratitis, and 2 cases of blindness in children due to inflammatory cataracts.

Of 160 semen samples tested, 28% were positive for Ebola RNA up to 9 months after disease onset. By 1 year, however, all semen samples tested negative, Dr. Delaporte said.

The investigators also found that among 131 patients discharged from an Ebola treatment center in the Guinean capital of Conakry and followed for a mean of 5 months, 20% had a score on the Center for Epidemiologic Studies depression scale (CES-D) that indicated the patients could benefit from psychological or psychiatric interventions.

Viral reservoir in semen?

In the second study, Dr. Sissoko and colleagues enrolled 26 men who had been discharged from three Ebola treatment units in coastal regions of Guinea from February through June, 2015. The investigators obtained semen specimens every 3-6 weeks until two consecutive samples were negative for Ebola virus on reverse transcriptase polymerase chain reaction testing (RT-PCR).

In all, 19 of the men had semen positive for Ebola RNA at baseline. At a median of 250 days of follow-up 25% of patients continued to have semen positive for Ebola.

The investigators used linear mixed modeling to estimate that at 11 months, approximately 10% of patients will continue to shed Ebola virus in semen, Dr. Sissoko said.

The investigators recommend testing semen samples from each man who has recovered from an Ebola infection until the semen test negative on two consecutive samples.

Both studies were supported by INSERM. Dr. Delaporte and Dr Sissoko reported having no conflicts of interest.

BOSTON – A majority of Ebola virus survivors continue to have significant physical, psychological, and sociological consequences for an extended period after discharge, investigators report.

Among 417 Ebola virus survivors enrolled in a follow-up study in Guinea, about 80% had residual clinical signs up to 9 months after discharge, reported Dr. Eric Delaporte of the French National Institute of Health and Medical Research (INSERM) and Montpellier (France) University.

Results of a second, small study, also from Guinea, suggest that up to 10% of men infected with Ebola have semen that remains positive for the virus for nearly a year after disease onset, said Dr. Daouda Sissoko of INSERM in Bordeaux, France.

“The results describe a post-Ebola syndrome with frequent clinical symptoms long after discharge, the gravity of ocular complications, long-term RNA positivity in semen, and the frequency of psychological consequences of the disease,” Dr. Delaporte said at a media briefing prior to presentation of the data in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

Dr. Delaporte is a coinvestigator in the Postebogui Cohort Study looking at Ebola survivors in Conakry and Macenta, Guinea. The goals of the study are to provide follow-up care for survivors and to describe the clinical, biologic, virologic, immunologic, and psychosocial consequences of infection with Ebola virus.

At CROI 2016, investigators reported on the first 417 patients enrolled, including 60 children. The median age was 28 years.

The investigators found that 46% of patients reported joint pains or other rheumatologic signs, 32% had neuropsychiatric signs, 29% reported chronic headache, 22% reported fatigue, and 16% had ophthalmologic signs,

Ophthalmic slit-lamp examinations in 160 patients showed 24 cases of uveitis, 4 cases of episcleritis, 2 cases of keratitis, and 2 cases of blindness in children due to inflammatory cataracts.

Of 160 semen samples tested, 28% were positive for Ebola RNA up to 9 months after disease onset. By 1 year, however, all semen samples tested negative, Dr. Delaporte said.

The investigators also found that among 131 patients discharged from an Ebola treatment center in the Guinean capital of Conakry and followed for a mean of 5 months, 20% had a score on the Center for Epidemiologic Studies depression scale (CES-D) that indicated the patients could benefit from psychological or psychiatric interventions.

Viral reservoir in semen?

In the second study, Dr. Sissoko and colleagues enrolled 26 men who had been discharged from three Ebola treatment units in coastal regions of Guinea from February through June, 2015. The investigators obtained semen specimens every 3-6 weeks until two consecutive samples were negative for Ebola virus on reverse transcriptase polymerase chain reaction testing (RT-PCR).

In all, 19 of the men had semen positive for Ebola RNA at baseline. At a median of 250 days of follow-up 25% of patients continued to have semen positive for Ebola.

The investigators used linear mixed modeling to estimate that at 11 months, approximately 10% of patients will continue to shed Ebola virus in semen, Dr. Sissoko said.

The investigators recommend testing semen samples from each man who has recovered from an Ebola infection until the semen test negative on two consecutive samples.

Both studies were supported by INSERM. Dr. Delaporte and Dr Sissoko reported having no conflicts of interest.

BOSTON – A majority of Ebola virus survivors continue to have significant physical, psychological, and sociological consequences for an extended period after discharge, investigators report.

Among 417 Ebola virus survivors enrolled in a follow-up study in Guinea, about 80% had residual clinical signs up to 9 months after discharge, reported Dr. Eric Delaporte of the French National Institute of Health and Medical Research (INSERM) and Montpellier (France) University.

Results of a second, small study, also from Guinea, suggest that up to 10% of men infected with Ebola have semen that remains positive for the virus for nearly a year after disease onset, said Dr. Daouda Sissoko of INSERM in Bordeaux, France.

“The results describe a post-Ebola syndrome with frequent clinical symptoms long after discharge, the gravity of ocular complications, long-term RNA positivity in semen, and the frequency of psychological consequences of the disease,” Dr. Delaporte said at a media briefing prior to presentation of the data in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

Dr. Delaporte is a coinvestigator in the Postebogui Cohort Study looking at Ebola survivors in Conakry and Macenta, Guinea. The goals of the study are to provide follow-up care for survivors and to describe the clinical, biologic, virologic, immunologic, and psychosocial consequences of infection with Ebola virus.

At CROI 2016, investigators reported on the first 417 patients enrolled, including 60 children. The median age was 28 years.

The investigators found that 46% of patients reported joint pains or other rheumatologic signs, 32% had neuropsychiatric signs, 29% reported chronic headache, 22% reported fatigue, and 16% had ophthalmologic signs,

Ophthalmic slit-lamp examinations in 160 patients showed 24 cases of uveitis, 4 cases of episcleritis, 2 cases of keratitis, and 2 cases of blindness in children due to inflammatory cataracts.

Of 160 semen samples tested, 28% were positive for Ebola RNA up to 9 months after disease onset. By 1 year, however, all semen samples tested negative, Dr. Delaporte said.

The investigators also found that among 131 patients discharged from an Ebola treatment center in the Guinean capital of Conakry and followed for a mean of 5 months, 20% had a score on the Center for Epidemiologic Studies depression scale (CES-D) that indicated the patients could benefit from psychological or psychiatric interventions.

Viral reservoir in semen?

In the second study, Dr. Sissoko and colleagues enrolled 26 men who had been discharged from three Ebola treatment units in coastal regions of Guinea from February through June, 2015. The investigators obtained semen specimens every 3-6 weeks until two consecutive samples were negative for Ebola virus on reverse transcriptase polymerase chain reaction testing (RT-PCR).

In all, 19 of the men had semen positive for Ebola RNA at baseline. At a median of 250 days of follow-up 25% of patients continued to have semen positive for Ebola.

The investigators used linear mixed modeling to estimate that at 11 months, approximately 10% of patients will continue to shed Ebola virus in semen, Dr. Sissoko said.

The investigators recommend testing semen samples from each man who has recovered from an Ebola infection until the semen test negative on two consecutive samples.

Both studies were supported by INSERM. Dr. Delaporte and Dr Sissoko reported having no conflicts of interest.

BOSTON – A vaginal ring infused with the antiretroviral drug dapivirine is effective and safe for reducing HIV-1 infections in high-risk women; at least in women older than 21 who use it as intended, results of two large randomized trials suggest.

In the ASPIRE Trial, conducted from August 2012 through June 2015 in Malawi, South Africa, Uganda, and Zimbabwe, there were 71 HIV infections among 1,313 women assigned to use the dapivirine ring, compared with 97 among 1,316 women assigned to a placebo, a difference that translated into a 27% reduction in infections.

In the Ring Study, conducted in South Africa and Uganda, the drug-infused ring reduced infections in the overall population by 31%, compared with a placebo ring, reported Dr. Annalene Nel from the International Partnership for Microbicides in Paarl, South Africa.

“This is the first demonstration of a sustained-release approach for antiretroviral prevention, and HIV protection in this study, not surprisingly, was greater with greater adherence,” said ASPIRE lead investigator Dr. Jared M. Baeten of the University of Washington, Seattle, at a media briefing at the Conference on Retroviruses and Opportunistic Infections.

“The data from both studies show that the ring must be used consistently to achieve protection, and that protection can be achieved with consistent use,” Dr. Nel said at the briefing.

The ASPIRE results are also published online in the New England Journal of Medicine (2016 Feb 22. doi: 10.1056/NEJMoa1506110).

In both trials, the ring offered little or no significant protection for women aged 18-21. In ASPIRE, there was no benefit for the dapivirine ring in this age group, and in Ring, infections were 15% lower among younger women who received the active ring, compared with placebo.

­

The ASPIRE investigators noted that younger women tended to have lower objective markers of adherence, such as dapivirine levels in plasma and in used rings, suggesting that poor adherence could partly explain the lack of benefit in this age group. They also suggest that “the genital tract of women in this age group may be more susceptible to HIV-1 infection and potentially also more difficult to protect with antiretroviral prophylaxis strategies.”

Trial design

In each trial, sexually active, HIV-negative women aged 18-45 were enrolled and randomly assigned to receive a vaginal ring containing 25 mg of dapivirine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, or a placebo ring. The rings were replaced every 4 weeks. In ASPIRE, the randomization was on a 1:1 basis; in the Ring study, the randomization was 2:1, with twice as many women receiving the active ring.

Participants had monthly follow-up visits that included serologic testing, safety monitoring, and adherence counseling. Median follow-up in ASPIRE was 1.6 years. The Ring study was halted early at the recommendation of the data safety monitoring board because of a higher-than-expected incidence of HIV infections.

ASPIRE study

In addition to the overall 27% reduction in infections seen in ASPIRE, the investigators found that when they excluded data from two sites with lower rates of retention and adherence, the ring reduced infections by 37%.

A post hoc analysis showed significantly better protection for women over age 21 (P less than .001), but not for younger women (P = .45), a difference that correlated with reduced adherence.

The researchers noted that among women who acquired HIV, the rates of adverse medical events and resistance to antiretroviral agents were similar between the active ring and placebo groups.

Ring study

As of Oct. 16, 2015 – the data cutoff point for RING – there were 2,805 person-years of follow-up, and 761 women had completed 2 years of follow-up. There were a total of 133 post-randomization HIV-1 infections, 77 of which occurred among women assigned to the dapivirine ring, translating into an incidence of 4.08 per 100 person-years, and 56 of which occurred among women assigned to placebo, for an incidence of 6.10 per 100 person-years.

The overall reduction in infections in the active ring group in the Ring study relative to placebo was 31% (P = .0401). In a subgroup analysis of women over age 21, the dapivirine ring reduced infections by 37%.

The most common ring-related adverse events in this trial were abnormal uterine bleeding, pelvic discomfort and/or pain, suprapubic pain, and application site pain. Adverse-event rates, including product-related events, urogenital events, serious adverse events and death, were similar between the treatment arms.

Based on the results of the two trials, the International Partnership for Microbicides is planning an open-label extension study for the Ring cohort and submission of data for regulatory approval of the device.

The ASPIRE study was funded by the National Institutes of Health. The Ring Study was funded by the Bill and Melinda Gates Foundation, the U.S. President’s Emergency Plan for AIDS Relief, the U.S. Agency for International Development, and several European governments and organizations, and was conducted by the International Partnership for Microbicides.

Dr. Baeten and Dr. Nel reported having no financial disclosures.

BOSTON – A vaginal ring infused with the antiretroviral drug dapivirine is effective and safe for reducing HIV-1 infections in high-risk women; at least in women older than 21 who use it as intended, results of two large randomized trials suggest.

In the ASPIRE Trial, conducted from August 2012 through June 2015 in Malawi, South Africa, Uganda, and Zimbabwe, there were 71 HIV infections among 1,313 women assigned to use the dapivirine ring, compared with 97 among 1,316 women assigned to a placebo, a difference that translated into a 27% reduction in infections.

In the Ring Study, conducted in South Africa and Uganda, the drug-infused ring reduced infections in the overall population by 31%, compared with a placebo ring, reported Dr. Annalene Nel from the International Partnership for Microbicides in Paarl, South Africa.

“This is the first demonstration of a sustained-release approach for antiretroviral prevention, and HIV protection in this study, not surprisingly, was greater with greater adherence,” said ASPIRE lead investigator Dr. Jared M. Baeten of the University of Washington, Seattle, at a media briefing at the Conference on Retroviruses and Opportunistic Infections.

“The data from both studies show that the ring must be used consistently to achieve protection, and that protection can be achieved with consistent use,” Dr. Nel said at the briefing.

The ASPIRE results are also published online in the New England Journal of Medicine (2016 Feb 22. doi: 10.1056/NEJMoa1506110).

In both trials, the ring offered little or no significant protection for women aged 18-21. In ASPIRE, there was no benefit for the dapivirine ring in this age group, and in Ring, infections were 15% lower among younger women who received the active ring, compared with placebo.

­

The ASPIRE investigators noted that younger women tended to have lower objective markers of adherence, such as dapivirine levels in plasma and in used rings, suggesting that poor adherence could partly explain the lack of benefit in this age group. They also suggest that “the genital tract of women in this age group may be more susceptible to HIV-1 infection and potentially also more difficult to protect with antiretroviral prophylaxis strategies.”

Trial design

In each trial, sexually active, HIV-negative women aged 18-45 were enrolled and randomly assigned to receive a vaginal ring containing 25 mg of dapivirine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, or a placebo ring. The rings were replaced every 4 weeks. In ASPIRE, the randomization was on a 1:1 basis; in the Ring study, the randomization was 2:1, with twice as many women receiving the active ring.

Participants had monthly follow-up visits that included serologic testing, safety monitoring, and adherence counseling. Median follow-up in ASPIRE was 1.6 years. The Ring study was halted early at the recommendation of the data safety monitoring board because of a higher-than-expected incidence of HIV infections.

ASPIRE study

In addition to the overall 27% reduction in infections seen in ASPIRE, the investigators found that when they excluded data from two sites with lower rates of retention and adherence, the ring reduced infections by 37%.

A post hoc analysis showed significantly better protection for women over age 21 (P less than .001), but not for younger women (P = .45), a difference that correlated with reduced adherence.

The researchers noted that among women who acquired HIV, the rates of adverse medical events and resistance to antiretroviral agents were similar between the active ring and placebo groups.

Ring study

As of Oct. 16, 2015 – the data cutoff point for RING – there were 2,805 person-years of follow-up, and 761 women had completed 2 years of follow-up. There were a total of 133 post-randomization HIV-1 infections, 77 of which occurred among women assigned to the dapivirine ring, translating into an incidence of 4.08 per 100 person-years, and 56 of which occurred among women assigned to placebo, for an incidence of 6.10 per 100 person-years.

The overall reduction in infections in the active ring group in the Ring study relative to placebo was 31% (P = .0401). In a subgroup analysis of women over age 21, the dapivirine ring reduced infections by 37%.

The most common ring-related adverse events in this trial were abnormal uterine bleeding, pelvic discomfort and/or pain, suprapubic pain, and application site pain. Adverse-event rates, including product-related events, urogenital events, serious adverse events and death, were similar between the treatment arms.

Based on the results of the two trials, the International Partnership for Microbicides is planning an open-label extension study for the Ring cohort and submission of data for regulatory approval of the device.

The ASPIRE study was funded by the National Institutes of Health. The Ring Study was funded by the Bill and Melinda Gates Foundation, the U.S. President’s Emergency Plan for AIDS Relief, the U.S. Agency for International Development, and several European governments and organizations, and was conducted by the International Partnership for Microbicides.

Dr. Baeten and Dr. Nel reported having no financial disclosures.

BOSTON – A vaginal ring infused with the antiretroviral drug dapivirine is effective and safe for reducing HIV-1 infections in high-risk women; at least in women older than 21 who use it as intended, results of two large randomized trials suggest.

In the ASPIRE Trial, conducted from August 2012 through June 2015 in Malawi, South Africa, Uganda, and Zimbabwe, there were 71 HIV infections among 1,313 women assigned to use the dapivirine ring, compared with 97 among 1,316 women assigned to a placebo, a difference that translated into a 27% reduction in infections.

In the Ring Study, conducted in South Africa and Uganda, the drug-infused ring reduced infections in the overall population by 31%, compared with a placebo ring, reported Dr. Annalene Nel from the International Partnership for Microbicides in Paarl, South Africa.

“This is the first demonstration of a sustained-release approach for antiretroviral prevention, and HIV protection in this study, not surprisingly, was greater with greater adherence,” said ASPIRE lead investigator Dr. Jared M. Baeten of the University of Washington, Seattle, at a media briefing at the Conference on Retroviruses and Opportunistic Infections.

“The data from both studies show that the ring must be used consistently to achieve protection, and that protection can be achieved with consistent use,” Dr. Nel said at the briefing.

The ASPIRE results are also published online in the New England Journal of Medicine (2016 Feb 22. doi: 10.1056/NEJMoa1506110).

In both trials, the ring offered little or no significant protection for women aged 18-21. In ASPIRE, there was no benefit for the dapivirine ring in this age group, and in Ring, infections were 15% lower among younger women who received the active ring, compared with placebo.

­

The ASPIRE investigators noted that younger women tended to have lower objective markers of adherence, such as dapivirine levels in plasma and in used rings, suggesting that poor adherence could partly explain the lack of benefit in this age group. They also suggest that “the genital tract of women in this age group may be more susceptible to HIV-1 infection and potentially also more difficult to protect with antiretroviral prophylaxis strategies.”

Trial design

In each trial, sexually active, HIV-negative women aged 18-45 were enrolled and randomly assigned to receive a vaginal ring containing 25 mg of dapivirine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, or a placebo ring. The rings were replaced every 4 weeks. In ASPIRE, the randomization was on a 1:1 basis; in the Ring study, the randomization was 2:1, with twice as many women receiving the active ring.

Participants had monthly follow-up visits that included serologic testing, safety monitoring, and adherence counseling. Median follow-up in ASPIRE was 1.6 years. The Ring study was halted early at the recommendation of the data safety monitoring board because of a higher-than-expected incidence of HIV infections.

ASPIRE study

In addition to the overall 27% reduction in infections seen in ASPIRE, the investigators found that when they excluded data from two sites with lower rates of retention and adherence, the ring reduced infections by 37%.

A post hoc analysis showed significantly better protection for women over age 21 (P less than .001), but not for younger women (P = .45), a difference that correlated with reduced adherence.

The researchers noted that among women who acquired HIV, the rates of adverse medical events and resistance to antiretroviral agents were similar between the active ring and placebo groups.

Ring study

As of Oct. 16, 2015 – the data cutoff point for RING – there were 2,805 person-years of follow-up, and 761 women had completed 2 years of follow-up. There were a total of 133 post-randomization HIV-1 infections, 77 of which occurred among women assigned to the dapivirine ring, translating into an incidence of 4.08 per 100 person-years, and 56 of which occurred among women assigned to placebo, for an incidence of 6.10 per 100 person-years.

The overall reduction in infections in the active ring group in the Ring study relative to placebo was 31% (P = .0401). In a subgroup analysis of women over age 21, the dapivirine ring reduced infections by 37%.

The most common ring-related adverse events in this trial were abnormal uterine bleeding, pelvic discomfort and/or pain, suprapubic pain, and application site pain. Adverse-event rates, including product-related events, urogenital events, serious adverse events and death, were similar between the treatment arms.

Based on the results of the two trials, the International Partnership for Microbicides is planning an open-label extension study for the Ring cohort and submission of data for regulatory approval of the device.

The ASPIRE study was funded by the National Institutes of Health. The Ring Study was funded by the Bill and Melinda Gates Foundation, the U.S. President’s Emergency Plan for AIDS Relief, the U.S. Agency for International Development, and several European governments and organizations, and was conducted by the International Partnership for Microbicides.

Dr. Baeten and Dr. Nel reported having no financial disclosures.