Microbicide Trials: Implications for Young People

1. Microbicide Trials: Implications for Young People Dr SengeziweSibeko; MB ChB, FCOG, MS Epi Research Gynecologist (On behalf of Prof. QuarraishaAbdoolKarim) UNAIDS Inter-Agency Task Team on HIV and Young People (IATT/YP) 28-29 June 2011, Paris, France

2. Overview: • Revisiting CAPRISA 004 results • Post CAPRISA 004 trial • Epidemiology of HIV in high school learners • Enhancing effectiveness and impact of tenofovir • Combination HIV prevention strategies in schools • Summary

3. Summary of CAPRISA 004 Findings • Proof of concept that tenofovir gel can prevent HIV infection in women • 39% protection against HIV overall • 54% effective in women with high adherence • Proof of concept that tenofovir gel can prevent HSV-2 infection in women • 51% reduction in HSV-2 • No substantive safety concerns New hope and interest in microbicides and HIV prevention science

4. Reducing HIV in Women with Tenofovir Gel Regulatory Access Implemen-tation Enhancing effective-ness of tenofovir gel

5. The Urgent Need for New Prevention:Age & Gender Profile of HIV Infection: South Africa 10 Male Female 8 6 Prevalence (%) 4 2 0 <9 10-14 15-19 20-24 25-29 30-39 40-49 >49 Source: Abdool Karim Q, Abdool Karim SS, Singh B, Short R, Ngxongo S. AIDS 1992; 6: 1535-9

6. HIV Prevalence in High School Learners

7. HIV Prevalence in High School Learners by Gender

8. CAPRISA 007: Baseline HIV Prevalence by Age and Gender

9. CAPRISA 007: Baseline HIV and Pregnancy Prevalence At baseline, similar HIV and Pregnancy Prevalence

10. Stopping the HIV Epidemic in Rural KwaZulu-Natal – HIV Prevention in Young Women is Central!

11. HIV Prevalence in Pregnant Women in Rural Vulindlela, South Africa (2005-2008)

12. Changing the Picture of HIV Prevalence in Pregnant Women in Rural South Africa: Potential Impact of Tenofovir Gel

13. Reducing HIV in Women with Tenofovir Gel Regulatory Access Implemen-tation Enhancing effective-ness of tenofovir gel

14. CAPRISA 002: Do Raised Cytokines Increase the Risk of HIV Acquisition?

15. TRAPS: Does Tenofovir Prevent HIV in Women With & Without Raised Cytokines?

16. HIV Counselling and Testing Treatment of STIs Male circumcision Microbicides for women Coates T, Lancet 2000 Grosskurth H, Lancet 2000 Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 Abdool Karim Q, Science 2010 Treatment for prevention Positive behavioural prevention Donnell D, Lancet 2010 Cohen M, 2011 COMBINATION HIV PREVENTION Fisher J, JAIDS 2004 Female Condoms Felblum P, AIDS 2001 Cash Incentives CAP 007, HPTN 058 Pre-Exposure prophylaxis Oral PrEP for MSM Male Condoms Hanenberg RS, Lancet 1994 Behavioural Intervention Grant R, NEJM 2010 Post Exposure prophylaxis (PEP) • Abstinence • Be Faithful Vaccines Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included – this is focused on reducing sexual transmission Scheckter M, 2002 Rerks-Ngarm S, NEJM 2009

17. CAPRISA 010: Vulindlela Intensive Prevention (VIP) Trial

18. What is Already in Place in the Schools Selected for CAPRISA 010 • Department of Education Lifeskills Program - Abstinence & HIV risk reduction education • HIV Counselling and Testing • Access to male and female condoms • Medical Male Circumcision for young men • Linkage to CAT for care and treatment • Screening for Pregnancy, STIs and TB • Treatment of STIs • Need to strengthen SRH services especially access to contraceptive services – feasibility of SRH services in schools • Need data to inform provision of tenofovir gel to school girls

19. Preparing for VIP : Need to Understand HIV Acquisition in Female Learners • Identifying sexual networks in learners in high schools • Understanding coital activity in female learners

20. HIV Sequencing to Identify Sexual Networks

21. Summary • Epidemiological data highlight impetus for interventions for young girls • age-sex differences in HIV acquisition • 007 pregnancy and HIV data underscore the urgent and important need for SRH services in schools • Modelling data of potential impact of tenofovir gel on young people based on CAP 004 results encouraging • CAP 004 is the first step: • long journey to licensure, access and implementation - still no data on adolescents • Promise of CAP 004 results must be realised for adolescents • Stopping HIV infection in adolescent girls is key to stopping the HIV epidemic and benefitting adolescent girls – need also to understand sexual behaviour

22. Acknowledgements • Financial support: USAID & S African Dept of Science & Technology • Tenofovir & placebo gel: Provided by CONRAD & Gilead Sciences • FHI Statistical & regulatory support: S Cameron, D Sokal & D Taylor • Trial Oversight Committee: • CAPRISA: Q Abdool Karim, SS Abdool Karim • FHI: W Cates, L Dorflinger, and D Taylor • USAID: L Claypool, J Manning, J Spieler • CONRAD: H Gabelnick • LIFElab(TIA): B Okole, C Montague • Gilead Sciences: J Rooney, Howard Jaffe • DSMBmembers: K Mayer (Chair), E Bukusi, K Dickson, C Lombard & S Self. Independent DSMB statistician: M Chen • FHI Study monitors: S Combes, C. Katz, L McNeil & A Troxler • Research infrastructure & training: US NIH’s CIPRA Program & the Columbia University - Southern African Fogarty Training Program • CAPRISA 004 trial team • CAPRISA 004 participants • CAPRISA 004 seroconverters study team (TRAPS)

23. Acknowledgements • The Principals, Educators, SGB, Parents, DOE (PMB and Vulindlela District and Circuit office) • Royal Netherlands Embassy • MiET Africa • Department of Education • Department of Health • Centers for Disease Control and Prevention, Pretoria • PEPFAR • Fogarty international Center • Jeffrey Fisher, William Fisher, Deborah Cornman, Laramie Smith, and the CHIP team at the University of Connecticut • HIV sequencing for sexual networks: Simon Travers, Carolyn Williamson, Thola Bennie

24. CAPRISA Vulindlela Clinical Research Site, near Howick in KwaZulu- Natal Thank You !!!