Sexual and reproductive health, use and preferences for pre-exposure prophylaxis (PrEP) among young women at HIV risk in Uganda

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Prevention of HIV and other sexual and reproductive health (SRH) risks remains suboptimal among young women aged 15-24 years in sub-Saharan Africa. This group accounts for over 80% of annual HIV infections among 15-24-year-olds globally, alongside persistently high rates of unintended pregnancy (24-34%) and sexually transmitted infections (STIs) (24-38%), highlighting a substantial unmet need for effective, integrated prevention strategies. In Uganda, the national HIV prevalence is estimated at 4.9%, but the burden is unevenly distributed across regions and key populations. Among young women engaged in sex work, the incidence of unintended pregnancy remains high at 23.5 per 100 person-years, while STI prevalence is estimated at 27%. Unmet need for contraception among unmarried, sexually active young women is also substantial, ranging from 36% to 55%. This occurs alongside persistently high HIV incidence, with females aged 15-24 accounting for 78% of new infections within this age group in 2024. Oral pre-exposure prophylaxis (PrEP) remains the only widely available biomedical HIV prevention method in many settings. However, uptake, adherence, and continuation remain low among young women at substantial risk of HIV acquisition. Peer support has shown promise in improving SRH outcomes among young people but is not well documented in the context of oral PrEP delivery. Evidence suggests that uptake and sustained use improve when individuals can select prevention methods that align with their preferences and lifestyles. Understanding preferences for emerging PrEP options is therefore critical to inform future implementation. Given the overlapping risk factors for HIV, STIs, and unintended pregnancies, there is a strong rationale for integrated assessment and management of these outcomes. This doctoral research comprised four interrelated studies conducted among young women at high risk of HIV acquisition. Study I was nested within an oral PrEP implementation project and assessed uptake, adherence, and continuation. Studies II, III, and IV were conducted within another implementation project evaluating a peer support intervention designed to improve oral PrEP uptake and adherence, and followed participants for 12 months. Study I included 265 participants and applied a mixed-methods convergent parallel design to examine preferences for novel biomedical PrEP methods. These included oral pills, vaginal rings and hypothetical long-acting injectables, implants, and HIV vaccines. Participants received two structured educational sessions covering both currently available and potential future methods prior to preference assessment. Study II enrolled 394 participants and followed them for 12 months using a hybrid type-1 effectiveness-implementation design, including a randomized controlled trial and assessment of implementation outcomes. The study evaluated the effect of a co-created peer support intervention, delivered as structured peer education, on oral PrEP uptake and adherence. It also assessed feasibility, acceptability, and cost-effectiveness. Peer leaders delivering the intervention were trained and were themselves taking daily oral PrEP or anti- retroviral therapy. Study III was a qualitative sub-study (n=18) embedded within Study II and used in-depth interviews to explore participants lived experiences with the peer support intervention. Study IV was a prospective cohort study nested within Study II that examined determinants of SRH risks among participants over 12 months. Study I: Baseline findings showed that 73% of participants preferred long-acting PrEP methods (injectables, implants, or vaccines), while 26% preferred oral PrEP. Preference for long-acting methods was more common among older participants and those with higher SRH risk, such as multiple sexual partners or STIs indicating preference based on perceived higher risk (risk stratification). In contrast, preference was lower among those with partners living with HIV or with unknown HIV status. Key drivers of preference included longer duration of protection, discretion in use, and delivery modalities similar to familiar contraceptive methods. Study II: The peer support intervention did not significantly increase PrEP uptake but resulted in a two-fold increase in oral PrEP adherence among initiators. It was also found to be feasible, acceptable, and cost-effective, particularly when adherence was measured using urine tenofovir kit compared to pill counts. Sensitivity analyses demonstrated improved cost-effectiveness in higher HIV incidence settings (>2.5%). Study III: Participants reported largely positive experiences with peer support. They highlighted improved access to accurate information, which helped dispel misconceptions about PrEP, and increased motivation to initiate and continue use due to heightened risk perception, peer influence, and psychosocial support. They also developed practical behavioural skills that enabled integration of daily PrEP use into their routines. Non-disclosure of PrEP use was sometimes employed as a strategy to avoid stigma or negative social consequences. However, several contextual barriers persisted, including high mobility with limited access to PrEP services in new locations, busy schedules, stigma, partner disapproval, and experiences of intimate partner violence. Study IV: Over the 12-month follow-up period, high incidence rates were observed: HIV (2.86 per 100 person-years), STIs (47.2 per 100 person-years), and pregnancy (24.8 per 100 person-years). Participants dynamically adjusted prevention behaviors based on perceived risk (risk stratification). Evidence of risk compensation was observed, including inconsistent condom use with HIV- negative partners. Behavioural substitution between condoms and contraception contributed to sustained high STI rates, although no substitution was observed between contraception and oral PrEP use. Additional contextual factors including substance use, street-based client recruitment, intimate partner violence, and depressive symptoms also influenced SRH outcomes. Overall, these findings underscore the need to expand access to a broader range of PrEP options, particularly long-acting methods, implement and scale peer-led support strategies, and strengthen integration of HIV and SRH services. Addressing broader social and structural factors that shape young women's risk and engagement with prevention services will be critical to improving outcomes. List of scientific papers I. Preference for novel biomedical HIV pre-exposure prophylaxis methods among adolescent girls and young women in Kampala, Uganda: a mixed methods study. Mayanja Y, Kayesu I, Kamacooko O, Lunkuse JF, Muturi-Kioi V, Price MA. Front Public Health, Sec. Infectious Diseases: Epidemiology and Prevention. 2024;12(1369256). https://doi.org/10.3389/fpubh.2024.1369256 II. Effect of a peer support intervention for oral pre-exposure prophylaxis uptake and adherence among adolescent girls and young women at risk of HIV acquisition in Kampala, Uganda: a randomized controlled trial. Mayanja Y, Abaasa A, Katumba KR, Spinelli M, Kikaire B, Gandhi M, Kosidou K, Ekström AM, Ruzagira E. [Submitted] III. A qualitative study of peer education experiences and oral pre- exposure prophylaxis use among adolescent girls and young women at high risk of HIV acquisition in Kampala, Uganda. Mayanja Y, Kayesu I, Nabalwanyi Z, Kosidou K, Ekström AM, Mujumbusi L, Rwamahe R. Frontiers in Public Health. 2025;13(1635462). https://doi.org/10.3389/fpubh.2025.1635462 IV. Determinants of poor sexual and reproductive health outcomes among adolescent girls and young women at risk of HIV infection in Kampala, Uganda: Findings from a 12-month oral PrEP implementation project. Mayanja Y, Ruzagira E, Kusemererwa S, Kikaire B, Ekström AM, Abaasa A, Kosidou K. [Manuscript]

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