Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda

Abstract

Background: 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.

Conclusions: 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.

Fig 1. Screening, enrollment, and follow-up.

Reasons for ineligibility are not mutually exclusive. A total of 1,013 higher-risk HIV-1-serodiscordant couples were enrolled. Of the initially HIV-1-seronegative partners, 12 subsequently seroconverted to HIV-1 but were found to have HIV-1 RNA in archived plasma from the time of enrollment, indicating acute seronegative HIV-1 infection.

Fig 2. Couple ART and PrEP use over time.

This graph illustrates the overall distribution of ART use by HIV-1-infected partners and PrEP use by HIV-1-uninfected partners within the study partnerships, over follow-up. The proportion of couples using only PrEP for HIV-1 prevention declined over time, as HIV-1-infected participants initiated ART, as defined by the PrEP as a bridge to ART approach of the project. Through month 6, there was the greatest overlap between ART and PrEP; thereafter, couples with HIV-1 infected partners that initiated ART at or soon after enrollment begin to discontinue PrEP. The primary reason for couples using neither ART nor PrEP was missed visits, which were considered as not exposed to PrEP (since PrEP was distributed only at the study sites during the study period) nor to ART (which was assumed to have not been initiated until first reported).

Fig 3. HIV-1 incidence, expected versus observed.

Expected HIV-1 incidence was estimated from a counterfactual model, bootstrapping data from a comparable at-risk population of HIV-1-serodiscordant couples. The graphic presents results for the entire study population. The table details the overall population estimates as well as analyses stratified by gender of the HIV-1-uninfected partner and baseline plasma HIV-1 RNA concentrations of the HIV-1-infected partner.