HIV pre-exposure prophylaxis or “PrEP” offers HIV negative individuals the opportunity to significantly reduce the risk of acquiring HIV. Tenofovir disoproxil fumarate (TDF), also known as oral PrEP taken as a daily pill, has been scaled up in Kenya for numerous populations with substantial risk for HIV, including adolescent girls and young women (AGYW). For many AGYW who start oral PrEP, discontinuation rates are high and they do not benefit from long-term HIV protection. Newer PrEP products that are longer acting, including dapivirine-eluting vaginal rings and intramuscular injections of cabotegravir, offer for longer term protection and less dependence on the user. Following international normative guidelines, these products are being integrated into clinical guidelines in Kenya and other countries. For oral PrEP, a key strategy for efficient scale up was integration into existing programs, such as those for reproductive health care (e.g., family planning, antenatal, postabortal care) and we have been working in reproductive health clinics in Kenya to conduct implementation science to optimize the integration of oral PrEP. In our work, we have seen high levels of interest in PrEP yielding high frequency of PrEP initiation – 13-35% of eligible women ages 15-30 years in our family planning and post-abortal clinic partners. However, we have continued to see high levels of program drop out and non-adherence to PrEP. Barriers to PrEP continuation include AGYW desire for discretion and convenience. It is yet unknown if the availability of multiple HIV PrEP products will yield greater HIV prevention coverage (product access and adherence) for AGYW. Through this protocol, we will conduct a stepped wedge cluster randomized trial to determine the effect of multi-product PrEP on HIV prevention coverage. We will capacitate participating facilities to add injectable cabotegravir and dapivirine ring into their existing PrEP services that are offered to women seeking reproductive health care. We will also evaluate the program to determine fidelity to the provision of multiple PrEP products and the experiences of users and providers with the program. In summary, we will integrate novel PrEP products – dapivirine ring and injectable cabotegravir – into existing PrEP programs that reach women seeking reproductive health care at health facilities in Kenya. Our primary aim will be to determine whether the availability of multiple PrEP products to young women will result in greater frequency of PrEP initiation and persistence and we will also evaluate the choice-based PrEP program counseling and the experiences of providers and users with the program. Results from this study will be directly relevant to the Kenya national AIDS control program to guide scale up of new PrEP products to reach AGYW with sustained use and protection from HIV.

Oral pre-exposure prophylaxis (PrEP) has been scaled up in Kenya for people with substantial risk for HIV, including adolescent girls and young women (AGYW) who experience some of the highest levels of HIV incidence. For many AGYW who start oral PrEP, discontinuation rates are high, limiting the length of time that they benefit from HIV protection. Newer PrEP products, including monthly dapivirine-eluting vaginal rings and 2-monthly intramuscular injections of cabotegravir, may provide longer protection as they rely less on the user to comply with daily adherence behavior. In Kenya, subsequent to recommendations from WHO and local regulatory approvals, these products are being integrated into clinical guidelines.

For oral PrEP, a key strategy for efficient scale up was integration into existing programs, such as those for reproductive health care (e.g., family planning, antenatal care, maternal and child health care), that offer routinely used services in the domain of sexual healthcare. Following our engagement with landmark clinical trials of oral PrEP efficacy, we have been working in these reproductive health spaces to conduct implementation science research to optimize PrEP integration, including training providers, developing linkages with national supply chain mechanisms for PrEP, and supporting providers and programs to overcome challenges. Through this work with AGYW, we have identified the importance of provider training and champions, normalizing HIV testing and counseling, and creation of social support mechanisms as components of PrEP programs. Despite documented high levels of interest in PrEP and moderate frequency of PrEP initiation – 13-35% of eligible women ages 15-30 years in our family planning and post-abortal clinic studies – we consistently observe high levels of program drop out, non- adherence to daily medication, and only moderate ability to track whether PrEP refills and re- starts align with fluctuating sexual behavior and potential exposure to HIV. These barriers to PrEP continuation are driven by AGYW needs for PrEP options that afford discretion, convenience, and safety.

HIV prevention advocates have championed the importance of having multiple prevention options that provide opportunities for individuals to choose a method and switch to different methods over the course of a lifetime of prevention. In the contraceptive field, the availability of multiple products has afforded choice and reduced unintended pregnancy. It is yet unknown if the availability of multiple HIV PrEP products will actually afford greater HIV prevention coverage. We plan to conduct a large trial of HIV prevention coverage when multiple PrEP options are available, leveraging systems and expertise within health facilities providing reproductive health services to AGYW. This protocol describes operationalization of a stepped wedge cluster randomized trial to determine the effect of multi-product PrEP programs on HIV prevention coverage over 6 months of follow up. Additionally, the protocol describes methods to evaluate the program. Data will be used to inform PrEP delivery guidance in Kenya and countries with a similar HIV epidemic and prevention environment.