ABSTRACT Maximizing access and minimizing costs of delivery are key challenges for optimizing the public health impact of pre-exposure prophylaxis (PrEP) for HIV-1 prevention. In Africa, PrEP will be added to an already-burdened health infrastructure and the ability of public health systems to afford PrEP will necessitate making its delivery cost-effective and time-efficient. PrEP delivery programs will be cost-sensitive to staffing needs (e.g., frequent clinic visits), and patients may not continue PrEP if the opportunity costs (e.g., travel to and waiting in clinics) are high. HIV-1 testing is central to PrEP delivery: testing at-risk persons is the first step for PrEP initiation and ongoing HIV-1 testing is essential for PrEP delivery. Like PrEP, HIV-1 self-testing is a new innovation and its opportunities to improve HIV-1 prevention have not yet been fully realized. We hypothesize that HIV-1 self- testing could be used to streamline PrEP delivery – specifically through decreasing the frequency of PrEP follow- up clinic visits by having self-tests at home replace clinic-based testing. New whole blood-based HIV-1 self- testing kits are potentially more affordable than oral fluid tests and may result in greater patient and provider confidence. With a multidisciplinary collaborative team, we propose to address key access and cost of delivery challenges for PrEP by using the new modality of HIV-1 self-testing. We will conduct an individually-randomized trial using a non-inferiority design among 495 women and men in Kenya initiating PrEP who will be randomly assigned to either: quarterly clinic visits with in-clinic blood-based HIV-1 testing (standard of care arm) or six- monthly clinic visits with HIV-1 self-testing at home for quarters between clinic visits (self-testing arm); those assigned to self-testing will be assigned to either oral fluid-based or blood-based testing. The population will include heterosexual HIV-1 serodiscordant couples (n=165 with HIV-1 uninfected men and n=165 with HIV-1 uninfected women) and HIV-1 uninfected women at risk (n=165). The outcomes at 6 and 12 months will be PrEP adherence (PrEP detection in blood samples and persistence in obtaining refills), completion of HIV-1 testing, and safety (including side effects and social harm). We will integrate mixed-methods work to understand user experiences, preferences, provider options, barriers, and facilitators related to HIV-1 self-testing within the PrEP context, to explore impressions of the two self-testing modalities (blood and oral fluid), and to consider the effect of gender and couple status on our findings. Finally, we will also use microcosting and mathematical modeling to assess the cost and cost-effectiveness of HIV-1 self-testing to optimize PrEP delivery. Combining self-testing and PrEP brings together two cutting-edge interventions, and the simple HIV-1 self-testing strategy in this application could improve PrEP’s cost-effectiveness, reach, and impact without sacrificing HIV-1 protection and safety. Given the time-sensitive nature of this question, and leveraging our experience, we propose to conduct this work in 3.5 years.

PROJECT NARRATIVE Pre-exposure prophylaxis (PrEP) and HIV-1 self-testing are new and powerful HIV-1 prevention tools; delivering these strategies will require approaches that are time- and cost-efficient, for patients, care providers, and the health care system. In a highly innovative study bringing these two new tools together, we propose to use HIV-1 self-testing to reduce the frequency of clinic visits for persons taking PrEP, and we will evaluate the effectiveness and safety of our approach using a randomized, non-inferiority trial among women and men initiating PrEP in Kenya. We hypothesize that using HIV-1 self-testing to replace frequent clinic visits for persons on PrEP will not reduce PrEP adherence or continuation of use, will be highly acceptable to patients and providers, and will be associated with reduced health system costs.