New Approaches to HIV Prevention: Present Status, Future Hopes

1. New Approaches to HIV Prevention:Present Status, Future Hopes Willard Cates, Jr., MD, MPH Family Health International Contraceptive Technology Conference March 31, 2007

2. Key Topics • HIV prevention rationale • HIV prevention approaches • Current trials • Future directions

3. HIV Prevention Research - Why • Continued spread of HIV • Clear moral imperative to conduct prevention science

4. 2007 – Do the HIV Math • Major success in ART access – 1.65 M on treatment, BUT • 4.3 M new HIV infections • We’re losing our fight against HIV

5. Routes • Sexual • Blood • Perinatal Reduce High Risk Behavior Rx STDs Block with Barriers Circumcision Vaccine ART PREP Rx OIs Perinatal Rx HIV Interventions to Prevent HIV HIV+ HIV+ Newly HIV+ HIV-

6. Contraceptive Pregnancy Rates Spermicides Diaphragm w/spermicides Female condom Male condom Oral Contraceptives IUD (TCu-380A) Rate during perfect use Female/male sterilization Rate during typical use Implant/Depo-Provera 0 10 20 25 5 15 Percent of Women Pregnant in First Year of Use Source: Trussell (2004); NCHS (2005)

7. HIV Prevention Tools - Infection Rates Abstinence Microbicides Diaphragm Female condom Male condom Oral Acyclovir Oral ARV Rate during perfect use Male circumcision Rate during typical use Vaccines 0 40 60 80 20 Percent of Persons Infected after a Decade of Use

8. Risk of HIV Transmission, By Consistency of Condom Use, Discordant Couples 7 6.5 5.1 5 HIV Incidence/ 100 PY 3 0.9 1 0 Always Sometimes Never “Inconsistent” “Nonuse” “Consistent” Source: Davis and Weller (1999)

9. Male Circumcision – Biological Plausibility • Inner mucosa of foreskin is rich in HIV target cells • External foreskin/shaft keratinized and not vulnerable • After circumcision, only vulnerable mucosa is urethral meatus • Moist sub-preputial space increase HIV survival

10. Male Circumcision – 3 RCTs

11. Complications from Circumcision in Africa • Orange Farm Trial (ages 18-24 yrs) • Complication rate of 3.8% • Kisumu (ages 18-24 yrs) • Complication rate of 1.7% • Bungoma, Kenya • 17.5 % complication rate in medical settings • 35% complication rate in traditional settings

12. Topical Microbicides –Current Products BufferGel Carraguard Pro2000 Tenofovir

13. Diaphragm • RCT in Zimbabwe, S Africa • Diaphragm plus lubricant gel vs. condom • 4,500 participants enrolled • Results expected “soon”

14. Female Condoms • Biologic plausibility similar to male condoms • If made available, lowers overall level of unprotected acts • Emerging evidence on STD prevention when used consistently

15. Oral Acyclovir Prophylaxis • Acquisition – HSV+, HIV- subjects – HPTN 039 – USA and global – 3,000 participants – MSM, MSW – Results expected 2007 • Transmission – HSV+, HIV+ subjects – Gates – US and global – 3,600 HIV discordant couples – Results expected 2009

16. Oral ARV Pre-exposure Prophylaxis • Focus for prevention trial ethics/politics • Studies in multiple populations globally • Testing 3 transmission routes • Different drugs and regimens • West Africa TDF safety data – summer ’06, International AIDS Meeting

17. West Africa TDF Conclusions • Daily oral use of TDF in HIV-uninfected women was not associated with increased adverse events • No evidence of risk compensation • Acceptability of and adherence to TDF regimen were possible • Effectiveness could not be evaluated conclusively

18. ARV Treatment as Prevention • Viral load importance • HPTN 052 – 8 sites, 5 countries • Pilot phase completed • Full trial – 1,760 discordant couples

19. Contraception as HIV Prevention Willard Cates, Jr., MD, MPH Family Health International HIV Prevention Trials Conference March 29, 2007

20. Contraception is HIV Prevention Willard Cates, Jr., MD, MPH Family Health International HIV Prevention Trials Conference March 29, 2007

21. WHO Four Element PMTCT Strategy Prevention of HIV in uninfected women, especially young women Prevention of unintended pregnancies in HIV-infected women Prevention of transmission from an HIV-infected woman to her infant Support for mother and family Element 1 Element 2 Element 3 Element 4 General Population FP & Postnatal Clinics HIV Care/ Treatment ANC Clinics

22. Effect of Current Contraceptive Use by HIV+ Women • 577,000 unintended births averted annually in HIV+ women – implications for orphanage • 30% vertical transmission if no ARTs • 173,000 HIV+ births prevented annually • If unmet need for contraception addressed, this number could be doubled. Source: Reynolds, et al., 2005

23. Contraception – The BEST KEPT SECRET in HIV Prevention • Effective contraception for HIV-infected women who do not wish to become pregnant • Prevents more infants becoming infected than NVP • Decreases the number of future orphans • Key Question – how best to promote the SRH/HIV linkages?

24. SRH and HIV: Key Linkages Key Linkages Learn HIV status Promote safer sex Optimize connection between HIV/AIDS and STI services Integrate HIV/AIDS with maternal and infant health • HIV/AIDS • Prevention • Treatment • Care • Support • SRH • Family Planning • Maternal & infant care • Management of sexually transmitted infections • Management of other SRH problems Source: WHO/UNAIDS, IPPF/UNFPA (2005)

25. Future Directions • Acute HIV infection • 3rd generation microbicides • New formulations and combinations

26. Transmission Efficiency

27. Simultaneous Prevention Interventions in Early HIV Infection Interval

28. Topical Microbicides –3rd Generation Products ACID FORM VivaGel CAP TMC 120 UC-781

29. Microbicides – Regimens/Formulations • Coitally – gel, film, suppository, oral • Daily – gel, oral • Longer Acting – vaginal ring, sponge

30. HIV Prevention - 2007 • HIV prevention regaining momentum • Combination of methods necessary – ABC…Z (The full alphabet) • Current methods are working – when used • New methods being evaluated