UZ-UCSF Annual Research Day 8 April 2016 MTN 034: Next Steps in Understanding HIV Prevention in Young African Women UZ-UCSF Annual Research Day 8 April 2016

Rationale for evaluating PrEP & vaginal rings in young African women Given lower adherence & efficacy with Truvada (FTC/TDF) & dapivirine (DPV) ring among young women in clinical trials: Need to assess biological factors that may influence safety & efficacy of products in adolescents & young women Need to understand acceptability and adherence to oral PrEP & vaginal rings Need safety data in <18 year old women for regulatory approvals Bullet point 2: what would increase acceptability and adherence – are cash incentives required (CCT). CCT has shown to decrease HIV incidence – an RCT conducted in Lesotho demonstrated that offering financial incentives reduced HIV acquisition by 25% over a 2 year period. Promising results also seen in Malawi with a 64% few HIV infections in intervention group. Bullet point 3: understanding the factors that contribute to young girls engaging in relationships, often transactional in nature, with older men. Bilogical factors: the effect of recent HSV2 infection on genital inflammation and the various vaginal cleansing practices on the vaginal microbiome.

MTN 034 Purpose: To assess safety and adherence of the Dapivirine (25 mg) Vaginal ring and Truvada (FTC /TDF) Tablet amongst African adolescent and young women Study Population: Healthy, HIV-uninfected, 300 adolescent females (15 - 17 years old) and 150 young women (18-21 years old) on effective contraception - Study Duration: 73 weeks of follow-up per participant

4 Sites across 3 countries Uganda Zimbabwe South Africa Study Sites: South Africa: eThekwini, Verulam CRS; Uganda: MU-JHU Research Collaboration CRS; Zimbabwe: Zengeza CRS These 3 countries are part of the 10 with high adolescent infection identified by PEPFAR for the DREAMS iniative.

Cross Over Study design Monthly dapivirine VR Daily oral TDF/FTC PrEP Proposed changes based on ASPIRE results: Add 150 additional participants aged 18-21 Add a third period during which young women will be allowed to select their preferred product Preference at beginning of study (after counseling & being shown TDF/FTC pill & dapivirine VR) Change in preferences over 6 months after each phase of oral PrEP or dapivirine VR Choice of product after using both oral PrEP and dapivirine VR

Thank you If we empower young women and adolescents to prevent HIV, we will fast track the end of HIV epidemic UNAIDS 2015. Thank you