Arresting the HIV epidemic in rural South Africa: Using innovations in intervention design and evaluation to reduce sexual transmission of HIV in adolescents and youth.

Research Question: I will use participatory research with patients and public involvement (PPI) in a HIV prevention programme that is embedded within a population-based longitudinal HIV incidence cohort of ~20,000, 16-29-year olds in rural KwaZulu-Natal to answer: Will risk-differentiated and tailored biosocial interventions developed with, and delivered by young people reduce transmissible HIV in 16-30-year olds?

Are interventions cost-effective? Is it feasible to deliver interventions with fidelity?

Background: Antiretroviral therapy (ART) through universal test and treat and HIV pre-exposure prophylaxis (PrEP) can substantially reduce HIV-related mortality, morbidity and incidence.

However, innovation in HIV prevention has outpaced the ability to implement and thus HIV remains the single largest health problem in South Africa.

Effective Individual-level prevention have not translated into population-level impact because this requires high coverage among adolescents and youth who are hard to engage.

Aims and objectives: The goal of my fellowship is to stem the HIV epidemic and it's negative impact on young people in SA through effective implementation of advances in HIV prevention.

Specific aim one: I will use community based participatory research to optimise risk-differentiated and tailored biosocial HIV prevention for young people in rural KZN Optimise the risk-differentiation (where more vulnerable and at risk individuals receive more support), and the psychosocial components of the intervention delivered by the peer navigators Establish safe clinical pathways to support decentralised PrEP, ART, and sexual health selfcare Use routine service use data to identify groups that need increased support Specific aims two: I will use a 4X2 factorial randomised controlled trial and process evaluation to evaluate the effectiveness and scalability of risk-differentiated and tailored biosocial HIV prevention delivered by peers to reduce the prevalence of sexually transmissible HIV among 16-30-year-old men and women Evaluate the effectiveness and cost effectiveness of the risk-differentiated and tailored biosocial HIV prevention delivered by peers to reduce the prevalence of transmissible HIV Conduct a process evaluation of the acceptability, feasibility, and equitable reach of each component of the intervention Timelines: The study will be in phases.

Phase one (0-18 months): I will build on ongoing funded formative work to optimise the intervention and refine the theory of change.

Phase two (18-48 months): I will use the unique and time-limited opportunity of a Wellcome funded multidisciplinary population research infrastructure and my PrEP implementation programme to test the effectiveness of the optimised intervention in a trial of n=3000 young people aged 16-30. Phase three (48-60 months): I will conduct the analysis and dissemination.

Output: Scalable, cost-effective interventions to reduce the negative impact of HIV on youth in South Africa, that is aligned with National and Provincial plans.

Robust and sustainable infrastructure and framework for participatory engagement and active PPI for young people to lead on innovations in delivery and new product introductions in rural KZN.

A platform to evaluate the population-level effectiveness of longer acting PrEP and other interventions in the pipeline.

Build local capacity to conduct innovative adaptive trials and implementation experiments through the KZN clinical trials consortium.