A new efficacy trial for an HIV vaccine -- only the seventh ever conducted in the history of the epidemic -- will start this November, delegates heard at the 21st International AIDS Conference (AIDS 2016) taking place this week in Durban. The HVTN 702 study will enroll 5400 men and women in southern Africa, and is planned to last for 4 years. In May it was announced that a pilot study, HVTN 100, had met the criteria for the vaccine being taken forward into the larger study. But this week was the first time researchers revealed how well it had met those criteria.
A pair of long-acting injectable antiretrovirals -- cabotegravir and rilpivirine -- administered once every 4 or 8 weeks maintained viral suppression in people who switched regimens with undetectable viral load, according to 48-week results from the LATTE-2 trial presented at the 21st International AIDS Conference (AIDS 2016) this week in Durban. A related qualitative analysis showed that study participants preferred long-acting injectables over pills for several reasons.
Australia plans an ambitious program of pre-exposure prophylaxis (PrEP) provision for gay men at high risk of HIV, with the aim of "virtually eliminating" HIV in the gay community by 2020, Iryna Zablotska from the University of New South Wales told delegates at the 21st International AIDS Conference (AIDS 2016) this week in Durban. PrEP roll-out is also underway in some countries in Kenya and South Africa.
Offering Truvada pre-exposure prophylaxis (PrEP) to the HIV-negative partner in a serodiscordant couple during the first 6 months after the HIV-positive partner starts antiretroviral therapy (ART) can serve as a "bridge" to further reduce the likelihood of HIV infection, researchers reported at the 21st International AIDS Conference (AIDS 2016) taking place this week in Durban, South Africa.
Studies have shown that effective antiretroviral treatment dramatically reduces the risk of onward HIV transmission -- a concept known as "treatment-as-prevention" -- and PrEP lowers the risk of infection by more than 90% of taken consistently. Putting these 2 highly effective approaches together may fill any gaps that can occur, for example, if a person has recently started ART and not yet achieved an undetectable viral load.
Jared Baeten from the University of Washington in Seattle presented findings from the Partners PrEP Demonstration Project, which looked at the real-world feasibility of PrEP plus ART for serodiscordant (mixed HIV status) couples in Africa.
The original Partners PrEP study, which Baeten first presented at the International AIDS Society conference in 2011, randomly assigned the HIV-negative partners in serodiscordant heterosexual couples in Kenya and Uganda to receive tenofovir/emtricitabine (the drugs in Truvada), tenofovir alone, or a placebo. (At the time, World Health Organization and country guidelines recommended ART initiation based on CD4 cell count, not for everyone diagnosed with HIV.)
The follow-up Partners PrEP Demonstration Project aimed to show whether an integrated combination of PrEP for negative partners plus ART for positive partners could further reduce the risk of HIV transmission. By the time this study started in November 2012, there was ample evidence that both PrEP and treatment-as-prevention were effective, and all participants were offered both interventions on an open-label basis (non-randomized).
The demonstration project was conducted at 4 centers in Kenya and Uganda that had hosted the original Partners PrEP randomized trial, but it enrolled a new cohort of 1013 serodiscordant heterosexual couples in which neither partner had ever used antiretroviral drugs.
The median age of participants was 30 years. In two-thirds of couples the woman was the HIV-positive partner. Positive partners had a median CD4 cell count of 436 cells/mm3 and a median viral load over 37,000 copies/mL. A majority (65%) said they'd had unprotected sex during the past month.
Upon enrollment the HIV-positive partner was offered combination ART in accordance with national guidelines -- under 350 cells/mm3 until mid-2013, then universal treatment thereafter -- while the HIV-negative partner was offered Truvada. PrEP was continued as long as the positive partner delayed starting treatment, or for the first 6 months after ART initiation, allowing time for viral load to become undetectable; PrEP was extended if the positive partner had treatment interruptions or known poor adherence.
The demonstration project selected couples based on a risk algorithm that gave scores from 1 to 10, depending on predictors of HIV risk including younger age, cohabitation rather than marriage, recent unprotected sex, male partners not being circumcised, and positive partners having a high viral load; couples with a score of 5 or higher were eligible for the study.
At the 2015 Conference on Retroviruses and Opportunistic infections, Baeten reported interim results showing that 2 initially HIV-negative partners seroconverted. In lieu of a placebo arm, the researchers used the incidence rate in the placebo arm of the original randomized Partners PrEP trial to estimate that 40 new infections would have been expected in the absence of ART and PrEP -- a risk reduction of 96%.
This week Baeten gave final updated results with follow-up data through June 2016, reflecting approximately 1700 person-years of follow-up.
By this time 91% of positive partners had started ART and almost all had achieved viral suppression (<400 copies/mL). Most (97%) of the negative partners offered PrEP accepted it. Couples used ART alone for 39%% of follow-up time, PrEP alone for 20%, overlapping ART and PrEP for 33%, and neither ART nor PrEP for 7%.
By the end of follow-up 4 new HIV infections had occurred, compared with 83 expected without ART or PrEP, for a relative risk reduction of 95%. Protection was similar regardless of sex, age, or pre-treatment viral load.
Adherence to both PrEP and ART was good during the demonstration project. Among HIV-negative partners who started PrEP and were randomly selected for drug level testing, 82% of blood samples had detectable tenofovir.
However, none of the newly infected individuals were actually using ART and PrEP consistently -- and in fact most were in couples that used neither.
One woman had broken up with her positive partner and stopped PrEP, while a second woman had a partner who did not yet want to start treatment and she also stopped PrEP; neither woman had detectable tenofovir in her blood at the time of infection. A third woman was a sex worker who used PrEP inconsistently. The sole man who was infected declined PrEP and had multiple partners.
"In this open-label demonstration project of integrated delivery of ART and PrEP for prevention in HIV serodiscordant couples, we observed virtual elimination of incident HIV," the researchers concluded.
"Interventions like this could have a substantial effect on the HIV epidemic," Baeten said at an AIDS 2016 press conference. "Both PrEP and ART are extremely important interventions that can virtually eliminate HIV transmission."
J Baeten, R Heffron, L Kidoguchi, et al. Integrated delivery of PrEP and ART results in sustained near elimination of HIV transmission in African HIV serodiscordant couples: final results from The Partners Demonstration Project. 21st International AIDS Conference (AIDS 2016). Durban, July 18-22. Abstract WEAC0105.
AIDS 2016. New Research Marks Important Step Forward in Understanding Real-World Use of PrEP. Press release. July 19, 2016.