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

Abstract

BackgroundAntiretroviral-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 FindingsBetween 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.ConclusionsIntegrated 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.

Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis

“…Targeting PrEP for those whose partners have a substantial or non-negligible risk of transmissible HIV is supported by the eligibility criteria for the Partners PrEP trial, 13 as well as data from the Partners Demonstration Project, in which providing PrEP to HIV-uninfected adults in serodiscordant relationships until six months after their HIV-positive partner began antiretroviral therapy was associated with a 96% (95% CI [confidence interval] 81%-99%) reduction in HIV incidence. 14 Our recommendations focus on heterosexuals in known serodiscordant relationships, because HIV prevalence in the general Canadian heterosexual population is low. 1 We did not identify any validated assessment tools for predicting incident infection in heterosexual adults in industrialized-world settings such as Canada.…”

“…13,14,[17][18][19] TDF alone, although efficacious in some trials, 13,15 is not recommended because of its smaller evidence base, and because it offers no major safety 20 or cost advantage (given the availability of generic TDF/FTC in Canada) over TDF/FTC. Of note, although TDF/FTC did not prevent HIV in two large trials among women in Africa, these negative results were driven by poor adherence to the study drugs.…”

Anti-Retroviral–Based HIV Pre-Exposure Prophylaxis for Women: Recent Advances and Next Steps

“…It was one of the two land marker studies that provided evidence to support US Food and Drug Administration approval for FTC-TDF PrEP. The study demonstrated PrEP HIV protective efectiveness against HIV infection of 67% (95% CI 44-81%, p < 0.0001) for TDF and 75% (95% CI 55-87%, p < 0.0001) for FTC/TDF [13] compared to person receiving placebo. The HIV protection efects of TDF and FTC/TDF were in women and men.…”

“…For TDF, eicacy among women was 71% and was 63% among men; for FTC/TDF, eicacy was 66% in women and 84% in men-all were statistically signiicant. In a follow-on open-label demonstration project of integrated delivery of ART and PrEP for prevention in HIV sero-discordant couples, the investigators observed virtual elimination of incident HIV [13].…”

“…Previous studies like the Partner's PrEP that assessed efectiveness of oral truvada and tenofovir for HIV prevention among sero-discordant couples in Kenya and Uganda have shown that when participants are given the active product through open-label access projects, even those with previous poor adherence during the clinical trial are now more likely to use product when they know they are now using the active product [13]. From a protection level of about 73% in the partner's PrEP, researchers have reported substantially reduced HIV risk of up to 95% when used with high adherence [17], Figure 1. …”