Integrating antiretroviral therapy (ART) for HIV-positive partners and Truvada pre-exposure prophylaxis (PrEP) for HIV-negative partners can nearly eliminate the risk of HIV transmission in serodiscordant couples, researchers reported at the 21st International AIDS Conference (AIDS 2016) taking place this week in Durban, South Africa.
Several studies have shown that effective antiretroviral treatment dramatically lowers the risk of onward HIV transmission—a concept known as “treatment-as-prevention”—- while PrEP taken consistently reduces the risk of infection by more than 90%. Putting the two approaches together may fill any gaps that could occur, for example, if a person has recently started ART and not yet achieved an undetectable viral load. In this strategy, PrEP serves as a “bridge” until treatment is fully effective.
Jared Baeten, MD, from the University of Washington in Seattle presented findings from the Partners PrEP Demonstration Project, which looked at the real-world feasibility of ART plus PrEP for serodiscordant (mixed HIV status) heterosexual couples in Kenya and Uganda.
In the original Partners PrEP study, HIV-negative partners were randomly assigned to take 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, so some of the HIV-positive partners did not start treatment.
Baeten first presented the study results at the International AIDS Society conference in 2011, showing that Truvada and tenofovir alone reduced the risk of HIV transmission by 73% and 62%, respectively.
The follow-up Partners PrEP Demonstration Project aimed to show whether integrating PrEP for negative partners plus ART for positive partners could further lower the risk. By the time this study started in November 2012 there was clear evidence that both PrEP and treatment-as-prevention worked, so all participants received ART and PrEP on an open-label (non-randomized) basis.
The demonstration project enrolled a new cohort of 1,013 serodiscordant heterosexual couples in which neither partner had ever taken antiretroviral drugs. Couples were selected using a risk algorithm that gave scores based on predictors including younger age, recent unprotected sex, male partners not being circumcised, and positive partners having a high viral load.
In two-thirds of couples, the woman was HIV-positive. Positive partners had a median CD4 count of around 400 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, HIV-positive partners were offered combination ART (recommended for all positive partners in serodiscordant couples regardless of CD4 count) and HIV-negative partners were offered daily Truvada. PrEP was continued if the positive partner delayed treatment or for the first six months after ART initiation, giving time for viral load to become undetectable.
At the 2015 Conference on Retroviruses and Opportunistic Infections Baeten reported interim results, showing that two HIV-negative partners had seroconverted. Based on the HIV incidence rate in the placebo arm of the original Partners PrEP trial, the researchers estimated that 40 new infections would have been expected without ART and PrEP—a risk reduction of 96%.
This week Baeten gave final updated results with data through June 2016. By this time 91% of positive partners had started ART, almost all of those had achieved viral suppression, and 97% of negative partners offered PrEP had accepted it. By the end of follow-up four new HIV infections had occurred, compared with 83 expected without ART or PrEP—a risk reduction of 95%.
Adherence to both ART and PrEP was found to be good during the demonstration project. A subset of HIV-negative partners on PrEP were randomly selected for drug level testing, and 82% of blood samples showed detectable tenofovir.
However, Baeten reported, none of the people who became infected used PrEP consistently, and in fact were in couples that used neither ART nor PrEP.
One negative 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. A third woman was a sex worker who used PrEP inconsistently. The only newly infected man declined PrEP and had multiple sex 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.”
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