Bridging the gap between research, MCC approval and public access to tenofovir gel

1. Bridging the gap between research, MCC approval and public access to tenofovir gel Quarraisha Abdool Karim on behalf of the CAPRISA 008 & CAPRISA 009 teams Parliamentary Portfolio Committee on Science & Technology 5 June 2013, Cape Town 1

2. Tenofovir Gel since CAPRISA 004: Next Steps • Confirmatory Trial – FACTS 001 • For MCC & FDA approval and licensure • Manufacture – ProPreven • Normative Guidelines (WHO/UNAIDS draft) • Implementation • CAPRISA 008 – integration into family planning services • CAPRISA 009 – treatment outcomes in women with HIV • Preparing for Public Access • Toolkit development for providers and users • Community Advocacy Efforts 2

3. Why does HIV continue to spread in South Africa? Seroprevalence of HIV infection in rural South Africa 10 Male AIDS 1992, 6:1535-1539 Female Quarraisha Abdool Karim, Salim S. Abdool Karim, Bipraj Singh*, Richard Short† and Sipho Ngxongo‡ 8 6 1990 Prevalence (%) 4 2 0 <9 10-14 15-19 20-24 25-29 30-39 40-49 >49 3

4. High rates of HIV among key populations: young women in Africa HIV in 15–24 year men and women (2008–2011) Young women have up to 8 times more HIV than men Zimbabwe Source: Adapted from UNAIDS 2012 4

5. HIV prevalence in young pregnant women in rural Vulindlela, South Africa (2009-2012) 5

6. Grassroots Advocacy EffortsSiyafuna 6

7. Key Goals of CAPRISA 008 • Provide post-trial access to tenofovir gel for HIV uninfected CAPRISA 004 study participants and community volunteers (UNAIDS Guidance point 19) • Develop and assess an implementation model for tenofovir gel provision through family planning services - Quality Improvement Model - Comprehensive SRH services 3. Collect additional safety data on tenofovir gel 7

8. CAPRISA 008: Implementing tenofovir gel in family planning clinics • Tenofovir gel provided by Family Planning service nurses with • DMPA, oral contraceptive and other method users – tenofovir gel provided every 3 months • For Nur-isterate users – tenofovir gel provided every 2 months 8

9. Components of the Toolkit • Providers, Users, Marketing & Demand Creation • Providers • “How to” Training Manual – SRH service provision to include tenofovir gel • Clinic procedures and systems to: • Monitor safety, pregnancy and HIV • Drug accountability & AE reporting • Counseling and support aids • Key information for M&E • Management of post-PrEP infection 9

10. Current status of CAPRISA 008 • First participant enrolled on November 5, 2012 • 425 participants screened; 359 enrolled and in follow-up • 43% of women enrolled are CAPRISA 004 high adherers • 54/516 women from CAPRISA 004 became infected prior to initiation of CAPRISA 008 • 10.5% seroconversion rate • Incidence rate of 3.8/100wy 10

11. Goal of CAPRISA 009 • Follow-up of HIV infected participants from CAPRISA 004 (control & intervention arm) to compare: • Disease progression • Therapeutic outcomes using a tenofovir containing treatment regimen • Monitor drug resistance • Target population: • 119 seroconvertors at end of CAPRISA 004 • 54 post-004 seroconvertors • Seroconvertors in CAPRISA 008 11

12. Current status of CAPRISA 009 • All seroconvertors who agree are in follow-up and care in CAPRISA 002/ Acute Infection Study until ARV treatment eligible • First patient initiated on ARV treatment in CAPRISA 009 in June 2011; • 34 initiated on ARV treatment • 15 from the tenofovir gel arm • 6 month treatment success rate – 88.9% 12

13. Summary • CAPRISA 008 provides an opportunity to generate evidence for implementation that will be required when a licensed product is available • Inclusion of research naïve volunteers from community completes ethical obligations and adds value to experience • CAPRISA 009 will provide additional safety data post-infection following exposure to tenofovir and provide data on concerns about drug resistance and therapeutic options for post-PrEP seroconvertors • Toolkit based on experiences and outcomes from 008 and 009 will enable rapid introduction and scale-up of a licensed product 13

14. Conclusions • Tenofovir gel potentially adds a new approach to empower women to take control of their own risk of HIV infection • CAPRISA 004 is the first step – it is likely that with time other products and formulations will surpass tenofovir gel • Post-trial access of tenofovir gel through CAPRISA 008 provides an opportunity to generate evidence for implementation that will fast track the timelag between potential licensure and public access 14

15. Acknowledgements • Financial support: • USAID through CONRAD • The South African Government’s Department of Science & Technology (DST) through the Technology Innovations Agency (TIA) • M-A-C AIDS fund through the Tides Foundation • Trial Oversight Committee: • CAPRISA: Q Abdool Karim, SS Abdool Karim, LE Mansoor • USAID (US): D Stanton, L Claypool • USAID (Pretoria): R Fertziger • CONRAD: H Gabelnick, G Doncel • DST/TIA: S Gumbi, G Loots • M-A-C AIDS/Tides: N Mahon, A Flynn • Gilead Sciences: J Rooney • Tenofovir & placebo gel: Provided by CONRAD & Gilead Sciences • FHI Statistical: M Chen • CONRAD regulatory support: JSchwartz, J Schafer • Research infrastructure & training: US NIH’s CIPRA Program & the Columbia University - Southern African Fogarty Training Program 15