Project: Combined HIV African Prevention Study: On demand Truvada and F/TAF Pre-exposure and Post exposure prophylaxis to protect adolescents from HIV
| Acronym | CHAPS (Reference Number: RIA2016MC-1616) |
| Duration | 01/04/2018 - 31/03/2021 |
| Project Topic | AIDS related deaths in adolescents have trebled since 2000 and are the leading cause of mortality in adolescents worldwide- renewed prevention strategies are required. Daily Pre-exposure Prophylaxis (PrEP) with Truvada is effective but compromised by adherence, toxicity and cost. Alternative drugs [e.g. less toxic tenofovir alafenamide (TAF)] and regimes (on-demand PrEP: around sexual activity)] exist but have not been widely evaluated. We aim to optimize PrEP and Post-exposure prophylaxis (PEP) dosing regimens for adolescents in sub-Saharan Africa. We hypothesize on-demand PrEP is highly acceptable/ feasible for at-risk adolescents, the regimen required for protection from insertive sex will be simpler than receptive anal sex, that F/TAF (TAF/Emtricitabine) provides greater protection than Truvada in PrEP and PEP and the window for PEP initiation is greater than current guidelines. Objectives: 1. Investigate the acceptability and feasibility of implementing daily and on-demand PrEP among adolescents in South Africa, Uganda and Zimbabwe A community-based study combined will determine critical attributes for PrEP uptake. Each country will conduct a quantitative survey (200 boys/200 girls) aged 13-24, four focus groups and 20 in-depth interviews to: • identify barriers and motivators towards the uptake of PrEP • describe the characteristics of adolescents willing to take daily versus on-demand PrEP • describe the role of gender dynamics in HIV prevention implementation 2. Optimize the dosing schedule for on-demand PrEP regimens for insertive sex Adolescent boys attending clinics for VMMC will be randomised to different PrEP regimes (including controls) prior to VMMC. Resected foreskins will be challenged with HIV ex-vivo. Effectiveness of Truvada and FTAF PrEP regimens will be determined and tissue bioequivalence of tenofovir and TAF compared to determine: • the minimal PrEP dosing that provides protection • plasma and foreskin tissue concentrations of FTC, tenofovir, TAF required for protection • safety/ tolerability of on-demand PrEP: Truvada versus F/TAF • PrEP effects on foreskin immunology 3. Optimise the time frame for initiating PEP for insertive sex: Foreskins (from controls) will be used to: • determine the maximum time after HIV exposure that PEP can be initiated effectively • compare Truvada and F/TAF PEP • investigate the contribution of a single PEP dose to provide HIV protection • HIV and PEP effects on foreskin immunology This is the first multi-country dosing/regime efficacy study for on demand PrEP and the first combined socio-behavioural study to determine critical attributes related to daily vs on demand of PrEP in adolescents in sub-Saharan Africa. |
| Network | EDCTP2 |
| Call | Clinical trials and operational research studies to optimise the use of products for poverty-related diseases in mothers, newborns, children and/or adolescents |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | King's College London | Coordinator | United Kingdom |
| 2 | Desmond Tutu HIV Foundation | Partner | South Africa |
| 3 | Imperial College of Science Technology and Medicine | Partner | United Kingdom |
| 4 | Karolinska Institutet | Partner | Sweden |
| 5 | London School of Hygiene and Tropical Medicine | Partner | United Kingdom |
| 6 | University of Cape Town | Partner | South Africa |
| 7 | University of Liverpool | Partner | United Kingdom |
| 8 | University of Zimbabwe | Partner | Zimbawe |
| 9 | Wits Health Consortium (Pty) Ltd | Partner | South Africa |