Long-acting HIV pre-exposure prophylaxis integrated with community-based sexual and reproductive health services in South Africa (LAPIS): study protocol for a hybrid (1a) cluster randomised controlled phase 3B trial of effectiveness and implementation

Background: Barriers and challenges associated with daily oral HIV pre-exposure prophylaxis (PrEP) contribute to poor uptake, low retention, and adherence rates among youth. Offering a choice of PrEP modalities integrated with peer support and delivered through community-based sexual and reproductive health (SRH) services will overcome these challenges. We describe the design of a trial to evaluate this approach at a population level. Methods: We are conducting a type 1a hybrid effectiveness, phase 3B, cluster randomised controlled trial (LAPIS) to evaluate the effectiveness and implementation of offering PrEP modality choices through community-based SRH services amongst youth aged 15–30 years living in rural Kwa-Zulu Natal, South Africa. LAPIS is nested within Thetha nami ngithethe nawe (Let’s Talk), an ongoing stepped-wedge trial with two periods investigating the effectiveness, implementation, and cost effectiveness of peer-led social mobilisation into decentralised integrated HIV and SRH services on the population prevalence of sexually transmissible HIV amongst youth. In the second period of Thetha nami, 40 trial clusters were randomised 1:1 to receive either a choice of PrEP modalities (oral PrEP, long-acting PrEP, i.e., two-monthly injectable cabotegravir (CAB LA) or dapivirine vaginal ring and HIV post-exposure prophylaxis [PEP] packs) or enhanced standard of care (ESoC) with oral PrEP only. All trial clusters are supported by peer navigators offering peer support and visited monthly by a mobile nurse-led clinic offering adolescent and youth-friendly HIV and SRH services. There are two primary outcomes: (1) effective uptake of PrEP or PEP, and (2) retention on PrEP, defined as attending at least one follow-up appointment after PrEP/PEP initiation, which are based on clinic data. Implementation outcomes are assessed using a mixed-methods and process evaluation following the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. Discussion: LAPIS is a pragmatic trial to evaluate the addition of long-acting PrEP modalities to daily oral PrEP within community-based SRH services. By offering PrEP choices, LAPIS adopts a person-centred approach to improve adherence and retention among youth, including hidden key populations. Findings will provide insights into the real-world implementation of CAB-LA. Trial registration: ClinicalTrials.gov Identifier—NCT06250504. Registered: 01 February 2024.