Shobha Shukla, Citizen News Service - CNS
The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, that was recently held in Vancouver, brought together a broad cross section of more than 6,000 HIV professionals from around the world, with a focus on moving science into practice.
“IAS 2015 will be remembered as the definitive moment when the world agreed earlier initiation of treatment is the best way to preserve the health of people living with HIV (PLHIV), and one of the best tools we have to slow HIV transmission to others,” said Julio Montaner, IAS 2015 Local Co- Chair and Director of the British Columbia Centre for Excellence in HIV/AIDS. “The new data (presented at the conference) will inform HIV treatment guidelines worldwide, and inspire governments, funders and health systems to act to save millions more lives.”
Latest data from several landmark studies, that were shared at the conference, provide new insights into treatment and prevention of this dreaded disease. Final results from two studies made a scientific case for initiating HIV treatment soon after diagnosis, and a third study shed new light on the non-daily use of pre-exposure prophylaxis (PrEP) among diverse populations at high risk for HIV.
The START (Strategic Timing of Antiretroviral Treatment) Study is the first large- scale randomized clinical study to establish that the initiation of antiretroviral therapy (ART) in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provides net benefits, over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. For the first time, Jens Lundgren of the University of Copenhagen presented full results of the study, which was stopped in May 2015 after preliminary data showed significant health benefits of earlier initiation of HIV treatment, regardless of the state of an individual’s immune health. Demonstarting multiple benefits of early HIV treatment, the study data demonstrate that starting on ART immediately after diagnosis, irrespective of CD4+ count, more than doubles an individual’s prospects of surviving and staying healthy, and considerably lowers the risk of developing AIDS or other serious illnesses.
The HPTN 052 study was designed to evaluate whether ART reduces sexual transmission of HIV. HPTN 052 Protocol Chair Myron Cohen of the University of North Carolina presented the final results of this ten years long landmark study, which showed that the risk of sexual transmission of HIV was greatly reduced among individuals whose infections were well suppressed by ART. The study showed that ART was good not only for the health of PLHIV, but also for the health of their uninfected partners.
Dr Cohen, lead investigator of the study, validated that ART can reduce transmission risks in sero-discordant couples—where one partner is infected and the other is not. Beginning in April 2005, the study enrolled 1,763 heterosexual adult couples (out of which 1171 couples remained till the end of the study) in 13 sites across 9 countries--Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe. Each couple included one partner with HIV infection and one without. Infected participants were assigned at random either to start antiretroviral therapy right away, while their immune system was relatively healthy, or to delay starting treatment until their immune system weakened or they developed an AIDS-defining illness. All participants received condoms and counseling on how to protect their partners from sexual transmission of HIV.
Once the investigators reported their landmark data in 2011, all infected study participants were offered the opportunity to begin ART right away, and the study continued for another 4 years, concluding in 2015. The latest findings re-confirm the significant ‘treatment as prevention (TasP)’ benefit to early ART for HIV prevention that was previously reported in 2011. Investigators reported at IAS 2015 that early start of ART reduced HIV transmission by 93% over the course of the study. Thus this large study provides robust evidence that ART started at any time in the course of infection can prevent heterosexual HIV transmission if viral suppression is achieved and maintained.
“Throughout our decade-long study with more than 1,600 heterosexual couples, we did not observe HIV transmission when the HIV-infected partner’s virus was stably suppressed by ART. These findings illustrate that treatment is an incredibly powerful tool for HIV prevention,” said Cohen.
The HPTN 067 study (also known as the ADAPT Study), evaluated the feasibility of PrEP dosing strategies--using daily, time-driven and event-driven dosing. The study, involving more than 500 participants, was conducted among heterosexual women in Cape Town, men who have sex with men (MSM) and transgender women in Bangkok, and MSM in Harlem in New York City. The latest data presented by HPTN 067 Protocol Chair and principal investigator of the study, Robert Grant of the Gladstone Institutes, provides new insights into the adherence to daily versus non-daily PrEP use, as well as patterns of sexual activity among women and MSM, with significant implications for PrEP rollout among heavily affected populations.
HPTN 067 was designed to evaluate the feasibility of non-daily PrEP regimens. The study evaluated acceptability and use of three different oral PrEP regimens-- daily, twice weekly (time driven) with a dose after sex, and one dose before and another after sex (event driven). The study was not designed to assess the efficacy of the different regimens in preventing HIV, and participants were informed that only the daily regimen has been proven effective to prevent HIV infection.
"The ADAPT study was designed to see if participants assigned to a non-daily dosing schedule would take their pills as prescribed. If participants were able to take fewer pills at times when they were not having sex, there could be greater satisfaction with PrEP services and cost savings if these regimens later proved to be effective and were recommended," said Grant.
In HPTN 067, after a six-week period to determine individual blood levels including four weeks of once-a-week directly observed pill taking, participants were randomly assigned to oral FTC/TDF in three dosage groups: daily dosing, time-driven dosing, and event-driven dosing. In all three dosing groups, dosing was not to exceed two pills per day or seven pills per week.
Results from each group of participants were analyzed separately. Thai MSM and transgender in Bangkok had the highest levels of coverage and adherence to the daily and time-driven dosing regimens, though coverage was significantly lower in the event-driven arm (85% of all sex events were covered in the daily arm, 84% in the time-driven arm and 74% in the event-driven arm).
In the cohort of the predominantly black MSM in Harlem, participants had a statistically significant higher level of coverage of sex acts in the daily arm (66% of all sex events were completely covered) compared to the non-daily arms (47% in the time-driven arm and 52% in the event-driven arm). Adherence was significantly higher among those assigned to the daily arm compared to those assigned to the non-daily arms.
In case of young single, black women participants in Cape Town, the study showed high levels of coverage of sex acts in the daily arm (75%) when they were aware that the product works and that they were receiving the active product (i.e. in the setting of an open label study, not a placebo-controlled study).
"HPTN 067 ADAPT study provides encouraging findings that diverse populations are able to take PrEP in a manner to achieve high coverage of sex acts," said HPTN Principal Investigator Myro Cohen. "The findings will motivate further exploration of ways to provide this important prevention intervention to populations."
A judicious combination of earlier initiation of HIV Treatment, TasP & Non-Daily PrEP could go a long way in developing better protocols that aim for ending HIV/AIDS. The Vancouver Consensus too calls upon the world leaders to implement HIV science and to act rapidly to provide access to immediate HIV treatment to all PLHIV in order to drive down HIV incidence, death, and long term costs.
Shobha Shukla, Citizen News Service - CNS
24 July 2015
The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, that was recently held in Vancouver, brought together a broad cross section of more than 6,000 HIV professionals from around the world, with a focus on moving science into practice.“IAS 2015 will be remembered as the definitive moment when the world agreed earlier initiation of treatment is the best way to preserve the health of people living with HIV (PLHIV), and one of the best tools we have to slow HIV transmission to others,” said Julio Montaner, IAS 2015 Local Co- Chair and Director of the British Columbia Centre for Excellence in HIV/AIDS. “The new data (presented at the conference) will inform HIV treatment guidelines worldwide, and inspire governments, funders and health systems to act to save millions more lives.”
Latest data from several landmark studies, that were shared at the conference, provide new insights into treatment and prevention of this dreaded disease. Final results from two studies made a scientific case for initiating HIV treatment soon after diagnosis, and a third study shed new light on the non-daily use of pre-exposure prophylaxis (PrEP) among diverse populations at high risk for HIV.
The START (Strategic Timing of Antiretroviral Treatment) Study is the first large- scale randomized clinical study to establish that the initiation of antiretroviral therapy (ART) in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provides net benefits, over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. For the first time, Jens Lundgren of the University of Copenhagen presented full results of the study, which was stopped in May 2015 after preliminary data showed significant health benefits of earlier initiation of HIV treatment, regardless of the state of an individual’s immune health. Demonstarting multiple benefits of early HIV treatment, the study data demonstrate that starting on ART immediately after diagnosis, irrespective of CD4+ count, more than doubles an individual’s prospects of surviving and staying healthy, and considerably lowers the risk of developing AIDS or other serious illnesses.
The HPTN 052 study was designed to evaluate whether ART reduces sexual transmission of HIV. HPTN 052 Protocol Chair Myron Cohen of the University of North Carolina presented the final results of this ten years long landmark study, which showed that the risk of sexual transmission of HIV was greatly reduced among individuals whose infections were well suppressed by ART. The study showed that ART was good not only for the health of PLHIV, but also for the health of their uninfected partners.
Dr Cohen, lead investigator of the study, validated that ART can reduce transmission risks in sero-discordant couples—where one partner is infected and the other is not. Beginning in April 2005, the study enrolled 1,763 heterosexual adult couples (out of which 1171 couples remained till the end of the study) in 13 sites across 9 countries--Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe. Each couple included one partner with HIV infection and one without. Infected participants were assigned at random either to start antiretroviral therapy right away, while their immune system was relatively healthy, or to delay starting treatment until their immune system weakened or they developed an AIDS-defining illness. All participants received condoms and counseling on how to protect their partners from sexual transmission of HIV.
Once the investigators reported their landmark data in 2011, all infected study participants were offered the opportunity to begin ART right away, and the study continued for another 4 years, concluding in 2015. The latest findings re-confirm the significant ‘treatment as prevention (TasP)’ benefit to early ART for HIV prevention that was previously reported in 2011. Investigators reported at IAS 2015 that early start of ART reduced HIV transmission by 93% over the course of the study. Thus this large study provides robust evidence that ART started at any time in the course of infection can prevent heterosexual HIV transmission if viral suppression is achieved and maintained.
“Throughout our decade-long study with more than 1,600 heterosexual couples, we did not observe HIV transmission when the HIV-infected partner’s virus was stably suppressed by ART. These findings illustrate that treatment is an incredibly powerful tool for HIV prevention,” said Cohen.
The HPTN 067 study (also known as the ADAPT Study), evaluated the feasibility of PrEP dosing strategies--using daily, time-driven and event-driven dosing. The study, involving more than 500 participants, was conducted among heterosexual women in Cape Town, men who have sex with men (MSM) and transgender women in Bangkok, and MSM in Harlem in New York City. The latest data presented by HPTN 067 Protocol Chair and principal investigator of the study, Robert Grant of the Gladstone Institutes, provides new insights into the adherence to daily versus non-daily PrEP use, as well as patterns of sexual activity among women and MSM, with significant implications for PrEP rollout among heavily affected populations.
HPTN 067 was designed to evaluate the feasibility of non-daily PrEP regimens. The study evaluated acceptability and use of three different oral PrEP regimens-- daily, twice weekly (time driven) with a dose after sex, and one dose before and another after sex (event driven). The study was not designed to assess the efficacy of the different regimens in preventing HIV, and participants were informed that only the daily regimen has been proven effective to prevent HIV infection.
"The ADAPT study was designed to see if participants assigned to a non-daily dosing schedule would take their pills as prescribed. If participants were able to take fewer pills at times when they were not having sex, there could be greater satisfaction with PrEP services and cost savings if these regimens later proved to be effective and were recommended," said Grant.
In HPTN 067, after a six-week period to determine individual blood levels including four weeks of once-a-week directly observed pill taking, participants were randomly assigned to oral FTC/TDF in three dosage groups: daily dosing, time-driven dosing, and event-driven dosing. In all three dosing groups, dosing was not to exceed two pills per day or seven pills per week.
Results from each group of participants were analyzed separately. Thai MSM and transgender in Bangkok had the highest levels of coverage and adherence to the daily and time-driven dosing regimens, though coverage was significantly lower in the event-driven arm (85% of all sex events were covered in the daily arm, 84% in the time-driven arm and 74% in the event-driven arm).
In the cohort of the predominantly black MSM in Harlem, participants had a statistically significant higher level of coverage of sex acts in the daily arm (66% of all sex events were completely covered) compared to the non-daily arms (47% in the time-driven arm and 52% in the event-driven arm). Adherence was significantly higher among those assigned to the daily arm compared to those assigned to the non-daily arms.
In case of young single, black women participants in Cape Town, the study showed high levels of coverage of sex acts in the daily arm (75%) when they were aware that the product works and that they were receiving the active product (i.e. in the setting of an open label study, not a placebo-controlled study).
"HPTN 067 ADAPT study provides encouraging findings that diverse populations are able to take PrEP in a manner to achieve high coverage of sex acts," said HPTN Principal Investigator Myro Cohen. "The findings will motivate further exploration of ways to provide this important prevention intervention to populations."
A judicious combination of earlier initiation of HIV Treatment, TasP & Non-Daily PrEP could go a long way in developing better protocols that aim for ending HIV/AIDS. The Vancouver Consensus too calls upon the world leaders to implement HIV science and to act rapidly to provide access to immediate HIV treatment to all PLHIV in order to drive down HIV incidence, death, and long term costs.
Shobha Shukla, Citizen News Service - CNS
24 July 2015