Background: Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. Objective: The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. Methods: The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. Results: The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake. Conclusions: The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings.
