TwySHE—an mHealth peer-navigator intervention to increase PrEP and contraceptive use among female university students in Zambia: study protocol of a hybrid effectiveness-implementation randomized controlled trial

Background: HIV and pregnancy complications are the leading causes of death among adolescent girls and young women (AGYW) in Eastern and Southern Africa (ESA). In this region, AGYW aged 15–24 years accounted for over 60% of new HIV infections in 2022. This region also has the highest rates of unintended pregnancy globally and an adolescent birth rate twice the global average. Female students in ESA are a neglected, high-risk subpopulation for HIV and unintended pregnancy. Despite high-risk sexual behaviors among female university students in ESA, few behavioral interventions have targeted the prevention of HIV and unintended pregnancies in this population. This study aims to determine the effect and implementation of an mhealth peer navigator intervention on female students’ pre-exposure prophylaxis (PrEP) and contraception use at a large public university in Lusaka, Zambia. Methods: After a campus-wide recruitment survey, we will 1:1 randomize 324 female university students aged 18–24 at high risk for HIV to the TwySHE intervention, consisting of one-to-one peer navigator support (HIV/sexual and reproductive health (SRH) education, risk awareness, informed decision making, and accessing health services) for 6 months facilitated by a mobile application; or the control (receipt of a list of local SRH services). Behavioral surveys will be done at baseline, 3, 6, and 12 months. The primary outcome is self-reported PrEP use by month 6 verified by a health provider. Secondary outcomes are modern contraception use by month 6, and PrEP and contraception persistence. Study records and exit interviews will capture factors related to the intervention’s reach, effectiveness, adoption, implementation, and maintenance. Discussion: Trainings for the research team and peer navigators delivering the intervention are complete. The trial began enrolling participants on March 14th, 2025. As of May 6, 2025, 105 participants have been enrolled. The findings of this study will establish the effectiveness and implementation of a novel peer navigator mhealth intervention to increase PrEP and modern contraception use and persistence. If effective, the intervention has the potential to ultimately contribute to efforts in Zambia and elsewhere to reduce unintended pregnancy and HIV acquisition among high-risk sub-populations of in-school AGYW. Trial registration {2a; 2b}: The study has been prospectively registered in ClinicalTrials.gov (NCT06852508). Registered on February 28, 2025, https://clinicaltrials.gov/study/NCT06852508?term=NCT06852508&rank=1