Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.
Methods and Findings
Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.
Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.
In a prospective implementation study, Jared Baeten and colleagues investigate integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1–serodiscordant couples in Kenya and Uganda.
Why Was This Study Done?
Each year, approximately 2 million people become infected with HIV-1, most through sexual transmission and a majority in Africa.
Antiretroviral medications effectively treat HIV-1 infection, and, in the last 5 y, pivotal clinical trials demonstrated that such medications can be used to prevent new infections as well, through treatment of HIV-1 infected persons to reduce their infectiousness and use as pre-exposure prophylaxis by HIV-1 uninfected persons to reduce their susceptibility.
Models for effective delivery of antiretroviral medications for HIV-1 prevention in Africa have not been evaluated.
What Did We Do and Find?
We conducted a prospective study of a novel delivery model for use of antiretroviral medications for HIV-1 prevention among just over 1,000 HIV-1-serodiscordant couples (i.e., couples in which one member was HIV-1 infected and the other uninfected) in Kenya and Uganda; couples had behavioral and biologic characteristics that put them at particularly enhanced risk of HIV-1, even compared with HIV-1-serodiscordant couples in general.
Both members of all couples were offered antiretroviral medications, and they were counseled on their HIV-1 prevention benefits; the study took a pragmatic and cost-minimizing approach, discontinuing the use of pre-exposure prophylaxis for the uninfected partner 6 mo after the infected partner initiated antiretroviral treatment.
The primary goals of the project were to evaluate the implementation of the delivery model, including uptake, adherence, continuation, and safety.
Part-way through the anticipated delivery period, it became clear that the approach was highly successful and that HIV-1 transmission rates were considerably lower than would have been anticipated (a 96% reduction compared to expected rates in a simulated model).
What Do These Findings Mean?
Antiretroviral medications have proven to be a powerful tool for preventing HIV-1 spread in clinical research studies; the results of this study show that a practical delivery approach in an implementation setting is feasible with high uptake and adherence and can virtually eliminate HIV1- transmission.
Wide-scale roll-out of use of antiretroviral medications for HIV-1 prevention could have substantial effects in reducing the global burden of new HIV-1 infections.