Multiple stakeholder discussions have noted that demonstration of deliverability and understanding adherence and sexual behavior in the context of ART for prevention and PrEP use outside of clinical trials are critical factors to consider in anticipating roll-out of these strategies. HIV-1 serodiscordant couples are a primary target for implementation of ART for prevention and PrEP, particularly for East Africa. Critical unanswered questions for successful implementation of antiretroviral-based HIV- 1 prevention include how to target these expensive prevention strategies to realize maximum population HIV -1 prevention benefits and whether HIV-1 infected persons with asymptomatic disease would accept ART to reduce their risk for transmitting HIV-1, at-risk HIV-1 negative persons would use PrEP, and both would sustain high adherence needed for high effectiveness. Couples may potentially have the opportunity to use ART or PrEP for prevention; however, costs would prohibit simultaneous use in most settings. Thus, staged use – i.e., PrEP until the HIV-1 infected partner initiates ART and achieves viral suppression – may be an effective and cost- effective approach [44], and it is the approach we propose. Successful implementation of ART and PrEP for prevention in HIV-1 serodiscordant couples will need to 1) target delivery to highest-risk couples, 2) respond to couples’ preferences for and barriers to use of PrEP and ART, 3) achieve high uptake and sustained adherence and 4) consider how to discontinue PrEP if the HIV-1 infected partner initiates ART. This study proposes to address these key questions.

Antiretroviral-based HIV-1 prevention strategies– including 1) antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and 2) pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition– are among the most promising new approaches for dramatically decreasing HIV-1 spread. A priority population for implementation of ART and PrEP for HIV-1 prevention is HIV-1 serodiscordant couples (i.e., one member is HIV-1 infected and the other uninfected). Stable, heterosexual African HIV-1 serodiscordant couples face high risk of HIV-1 transmission, from within the partnership and from outside partners, and are a priority population for prevention interventions. Importantly, during the past year, both ART (HPTN 052) and PrEP (Partners PrEP Study) have demonstrated high efficacy for HIV-1 protection when used by members of HIV-1 serodiscordant couples. Critical unanswered questions for successful implementation of antiretroviral-based HIV-1 prevention include how to target these strategies to the highest-risk couples and whether HIV-1 infected persons with asymptomatic disease would accept ART to reduce their risk for transmitting HIV-1, at-risk HIV-1 negative persons would use PrEP, and both would sustain high adherence needed for high effectiveness. This protocol describes an open-label prospective study among high-risk African HIV-1 serodiscordant couples to determine user preferences for ART and PrEP and to optimize targeted delivery and sustained use of these interventions.