Title: 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.
Funder: Department of Health and Social Care

Abstract: 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 supportSpecific 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 interventionTimelines: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.

Lay abstract: Aim: My goal is to bring the benefits of recent major advances in HIV prevention to stem the HIV epidemic and its negative impact on young people in South Africa. I will do this through a peer-led community-based package of biomedical HIV prevention and psychosocial support (biosocial intervention) that is tailored to the young persons need. i.e. more vulnerable and at risk young people will receive more support.Background: Despite huge advances in HIV treatment and prevention HIV related ill-health and death remains a huge problem in South Africa. 7.7 million people are living with HIV and young people bear the brunt of both the health and socioeconomic impact of the HIV pandemic. The anticipated doubling in number of young people over the next twenty years really underscores the urgency of developing scalable models of delivering HIV prevention alongside treatment.Design and methods: The study will be conducted amongst men and women aged 16-30 living in a poor and rural area of KwaZulu-Natal and will follow two phases: In the first 18 months we will use participatory research with patients and public involvement (PPI) to optimise Thetha Nami (a peer-navigator delivered HIV prevention intervention for young people).We will a) optimise the peer navigator needs assessment tool so that vulnerable and at risk individuals receive more support. b) refine the social support and peer mentorship components of the intervention. c) establish safe clinical pathways for delivery of sexual health self-care to young people. d) identify ways to use routine service use data to identify groups that need increased support.In the second 30 months we will test this optimised intervention in a randomised controlled trial.3000 men and women aged 16-30 will be selected at random from the study area, ensuring that there is gender and age balance. If they agree to participate they will be randomly offered one of four possible intervention combinations: a) usual care, which is clinic based HIV testing and treatment if positive and biomedical prevention if negative; b) the peer-led biosocial intervention c) the sexual health self-care kit and d).a combination of the peer-led intervention and sexual health self-care kits.The participants will then be followed up after 24 months for an interviewer administered survey and a finger prick test for HIV.The main outcome of the study is to measure the effect of the interventions on reducing sexually transmissible HIV. This is defined as participants remaining HIV negative, or, if living with HIV, starting antiretroviral therapy and having an undetectable HIV viral load. We will also measure the effect of the intervention/s on sexual and mental health and quality of life. PPI is integral to this study. We used PPI to iteratively co-create the peer-led intervention. We will engage young people throughout the study. This will include, but is not limited to, strengthening the youth advisory component of our community advisory board, delivery of interventions through peer-navigators, and involvement of youth on the project steering committee. I will use participatory dissemination workshops to understand the enablers and ensure that these interventions were equitable in their reach. Dissemination: The final output will be a well-defined and scalable implementation strategy to reduce the negative impact of HIV on youth in South Africa. It will comprise a feasible approach to identify those at risk, and then deliver an intervention to improve uptake and effective use of HIV prevention and care.By engaging our technical advisory group, that include service users and providers and health policy makers, from the inception we are confident that we will generate the evidence needed to scale-up the interventions.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;7.1 INDIVIDUAL CARE NEEDS
Health categories: INFECTION