1. Prevention Science Gaps and the HIV/AIDS Pandemic Quarraisha Abdool Karim, PhD Head: CAPRISA Women and AIDS Pogramme Associate Professor in Epidemiology, Columbia University Director: CU-SA Fogarty AITRP Presentation at the XVI International AIDS Conference, Toronto

2. Overview Need for prevention research Need for prevention research What works What works New Prevention Options New Prevention Options Challenges and Gaps Challenges and Gaps

3. Number HIV infected* Estimated % due to heterosexual transmission** Persons living with HIV 38.6 million 87% New infections 4.1 million 86% Estimated deaths 2.8 million 88% Global burden: Common Challenge Source: Joint UNAIDS and WHO AIDS epidemic update July 2006 ** Based on Joint UNAIDS and WHO AIDS Update 2004 *(conservative estimate)

4. HSex= heterosexual transmission IDU = transmission through injecting drug use MSM = sexual transmission among men who have sex with men Source: Joint UNAIDS and WHO AIDS epidemic update December 2005 Latin America 1.8 million HSex, MSM, IDU East Asia 870 000 HSex, IDU, MSM Eastern Europe & Central \Asia 1.6 milion IDU Sub Saharan Africa 25.8 million HSex Oceania 74 000 MSM Caribbean 300 000 HSex, MSM North America 1.2 million HSex, MSM, IDU North Africa & Middle East 510 000 HSex, IDU Western Europe 720 000 MSM, IDU South & South-East Asia 7.4 million HSex, IDU Geographical distribution: Concentrated and generalised epidemics

5. Source: Abdool Karim & Abdool Karim (eds). HIV/AIDS in South Africa, 2005 Generalised Epidemic: HIV infection in antenatal clinic attendees in South Africa 0 5 10 15 20 25 30 35 198819901992199419961998200020022004 Year Prevalence (%) of HIV

6. Source : Abdool Karim Q et al, AIDS 1992 Epidemiology: Gender differences 0 <910-14 JUN/JUL 92 15-1920-2425-2930-3940-49 2 4 6 8 10 Male Female Prevalence (%) Age and gender specific prevalence of HIV infection in rural South Africa

7. Age specific HIV prevalence in Vulindlela antenatal clinic attendees (2001-2004) Age group Prevalence 2001(n=349)2002(n=409)2003(n=225)2004(n=550) <2015%26%19%27% 20-2444%46%45%55% 25-2931%43%66%66% 30-3414%22%43%54% >3516%16%36%10% Total32%34%41%43% Carrara H, Makhaye G, Frohlich J, Kharsany ABM, Abdool Karim Q. Young women bearing the brunt of the HIV epidemic in rural South Africa: Temporal trends in HIV infection 2001-2004. In Prep. 35% of all ANC attendees are <20 years of age

8. Temporal changes in adult mortality rate for men in SA Source: Dorrington R, Bradshaw D, et al. Medical Research Council

9. Temporal changes in adult mortality rate for women in SA Source: Dorrington R, Bradshaw D, et al. Medical Research Council

10. Correlation between Viral Load and HIV Transmission 0 5 10 15 20 25 30 Viral load (HIV-1 RNA copies/ml) and HIV transmission Transmission rate per 100 Person-Years <400 400-3499 3500-9999 10 000-49 999 >50 000 Source: Quinn N, et al, N Eng J Med 2000 <400 400-3499 3500-9999 10 000-49 999 >50 000 <400 400-3499 3500-9999 10 000-49 999 >50 000 All subjects Male-to-Female Transmission Female-to-Male Transmission

11. Transmission efficiency “

12. HIV Prevention – what works Sexual transmission Sexual transmission ABC ABC Voluntary Counselling and HIV testing Voluntary Counselling and HIV testing STI reduction STI reduction Blood borne transmission Blood borne transmission Harm reduction for IDUs Harm reduction for IDUs SNEP SNEP Maintenance therapy Maintenance therapy Blood supply safety Blood supply safety Infection control in health care Infection control in health care PMTCT PMTCT ARV PREP ARV PREP Breastfeeding alternatives Breastfeeding alternatives Safe delivery Safe delivery

13. Access to existing HIV prevention methods

14. Current efficacy trials of new prevention methods InterventionSiteSponsor# of participants Male circumcisionKenya Uganda NIH Gates 2500 5000 1361 ♂, 7000♀ Cervical barriers (♀ diaphragms) South Africa, Zimbabwe Gates5045 ♀ PREP TNF Emtricitabine Thailand Botswana Peru CDC NIH 1600 1200 ♂&♀ 1499 MSM HSV-2 suppression acyclovir Peru, South Africa, USA, Zambia, Zimbabwe Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, Zambia NIH Gates 3277 ♂&♀ 3000 ♂&♀

15. Current efficacy trials of new prevention methods Microbicides Savvy (C31G) Buffergel CS Pro 2000 Carraguard Nigeria Malawi, South Africa, Tanzania, Zambia, Zimbabwe Nigeria Benin, Burkino Faso, India, South Africa, Uganda, Malawi, South Africa, Tanzania, Zambia, Zimbabwe South Africa, Tanzania, Uganda, Zambia, Zimbabwe South Africa USAID NIH USAID Gates / USAID NIH DFID Gates 2142 3220 2574 10000 6299

16. A Continuum of prevention research ABC VCT STI treatment Male circumcision Cervical barriers PREP HSV-2 suppression Maintenance therapy Microbicides Vaccines

17. Challenges and Gaps Knowledge of HIV status – integration of prevention and treatment Knowledge of HIV status – integration of prevention and treatment A continuum of prevention A continuum of prevention Uninfected – Acutely infected – established infection Uninfected – Acutely infected – established infection Bridging the gap between ABC and Vaccines Bridging the gap between ABC and Vaccines -circumcision, barriers, HSV-2, ARVs, genital health, adolescent risk reduction, microbicides -circumcision, barriers, HSV-2, ARVs, genital health, adolescent risk reduction, microbicides Capacity to conduct trials Capacity to conduct trials HR, Funds, Infrastructure, Cohorts HR, Funds, Infrastructure, Cohorts Increasing access to what works – whose responsibility? Increasing access to what works – whose responsibility? Criteria for advancing products/interventions for Phase III testing Criteria for advancing products/interventions for Phase III testing