JMIR Publications

ABSTRACT

Background:

Pre-exposure prophylaxis (PrEP) remains among the most efficacious interventions for preventing HIV, but effectiveness is often hampered by poor persistence. Although regional focus has often centered on young women and men who have sex with men, heterosexual men in Eastern and Southern Africa are a crucial group to engage and retain in PrEP care, improving health outcomes for men and interrupting HIV transmission chains. Men seeking sexually transmitted infection (STI) services represent an important group particularly vulnerable to HIV acquisition. Yet, few interventions have tested engagement and retention of these men in PrEP services. Systems navigation focuses on addressing barriers to healthcare access and enhancing comfort in a clinical setting and may be a compelling opportunity to improve persistent PrEP use among heterosexual men.

Objective:

This study will assess the effect of a systems-navigator facilitated HIV prevention package on PrEP persistence among heterosexual men seeking STI clinical services in Lilongwe, Malawi, at 26 weeks, as well as acceptability and barriers to implementation among key stakeholders. Insights will inform the feasibility of a future randomized controlled trial.

Methods:

In this single-site pilot Type I effectiveness-implementation hybrid randomized controlled trial, 200 heterosexual men seeking STI services and initiated on PrEP in Lilongwe, Malawi will be randomized (1:2) to standard-of-care PrEP services (SOC) or systems navigator-assisted PrEP care (intervention). Participants will be followed every 13 weeks for at least 26 and up to 52 weeks. PrEP use and engagement in care will be assessed through medical record review and intraerythrocytic tenofovir diphosphate (TFV-DP) measurement, using objective biomedical analyses via dried blood spot (DBS). Primary effectiveness and implementation outcomes include 26-week PrEP persistence (adapted to accommodate daily oral, event-driven oral, or injectable PrEP) and acceptability, respectively. Additional implementation outcomes include feasibility and cost. Exploratory objectives characterize preferences for PrEP modalities, perceived and experienced stigma, and the influence of gender norms on PrEP persistence. All clinical services, including provision of PrEP and PrEP safety monitoring, are being conducted by the Malawi Ministry of Health.

Results:

HPTN 112 was funded in November 2023. Study recruitment began in April, 2024 and closed in November 2024. As of February 3, 2025, the study has enrolled 199 participants, with follow-up expected through June 2025. No interim analyses were planned; data analysis for primary endpoints are expected in Summer, 2025.

Conclusions:

Improving PrEP use outcomes for heterosexual men in Eastern and Southern Africa is critical to interrupt HIV transmissions. This study offers unique insights into a low-resource, potentially scalable intervention, focusing on a group of men at particularly high risk of HIV acquisition – those with recent STIs. The hybrid RCT design answers clinically relevant effectiveness questions and addresses fundamental determinants that will inform future, multi-site implementation trials. Clinical Trial: Registered at clinicaltrials.gov, NCT06200545. Registered 2023-12-28, https://clinicaltrials.gov/study/NCT06200545.