1. Welcome to I-TECH HIV/AIDS Clinical Seminar Series 3 rd December 2009 Women and HIV R. Scott McClelland, MD, MPH

2. Overview Introduction to HIV epidemiology in women HIV risk reduction for women Effect of male circumcision on the risk of HIV acquisition in female partners Gender-specific issues in selecting an antiretroviral regimen

3. Percentage of Adults (15+) with HIV who are Women UNAIDS Report 2008

4. HIV in 15-25 year olds by sex UNAIDS Report 2008

5. Case 1: HIV Prevention 18 y.o. HIV-negative woman recently treated for gonorrhoeae. What proven strategies can reduce her risk of acquiring HIV? –A) Abstain, Be faithful, male latex Condoms –B) ABCs and treat STIs –C) Female condom –D) Pre-exposure prophylaxis –E) All of the above

6. WHO Statement on HIV and STIs WHO Fact Sheet on STI. Oct 2007 revision. A bstain from sexual intercourse B e faithful – Mutual long-term monogamy with HIV- negative partner C ondoms Prompt treatment of STIs –Both in high risk and general population

7. UNAIDS November 2009 New HIV infections reduced 17% over the past 8 years

8. Condom Quiz How much do you know about condoms?

9. Question 1 With consistent and correct use of condoms, the estimated rate of pregnancy at 12 months is closest to which range? –A. 0% –B. 1-4% –C. 5-8% –D. 9-12% –E. Over 12% WHO Fact Sheet No234. June 2000

10. Question 1 With consistent and correct use of condoms, the estimated rate of pregnancy at 12 months is closest to which range? –A. 0% –B. 1-4% –C. 5-8% –D. 9-12% –E. Over 12% WHO Fact Sheet No234. June 2000

11. Question 2 For typical condom use, the estimated rate of pregnancy at 12 months is closest to which range? –A. 5-10% –B. 10-15% –C. 15-20% –D. Over 20% WHO Fact Sheet No234. June 2000

12. Question 2 For typical condom use, the estimated rate of pregnancy at 12 months is closest to which range? –A. 5-10% –B. 10-15% –C. 15-20% –D. Over 20% WHO Fact Sheet No234. June 2000

13. Question 3 Condom failure – the device breaking or slipping off completely during intercourse – is common. –A. True –B. False WHO Fact Sheet No234. June 2000

14. Condoms do not break easily YouTube

15. Condoms do not break easily YouTube

16. Question 4 Longitudinal studies in men and women suggest that condoms reduce the risk of HIV infection by a rate that is closest to: –A. <50% –B. 50-65% –C. 65-80% –D. 80-95% –E. >95%

17. Question 4 Longitudinal studies in men and women suggest that condoms reduce the risk of HIV infection by a rate that is closest to: –A. <50% –B. 50-65% –C. 65-80% –D. 80-95% –E. >95%

18. Question 5 Longitudinal studies in women suggest that condoms reduce the risk of human papilloma virus (HPV) infection by at least: –A. 10% –B. 30% –C. 50% –D. 70% –E. 90% Winer et al. N Engl J Med 2006

19. Question 5 Longitudinal studies in women suggest that condoms reduce the risk of human papilloma virus (HPV) infection by at least: –A. 10% –B. 30% –C. 50% –D. 70% –E. 90% Winer et al. N Engl J Med 2006

20. Case 1: HIV Prevention 18 y.o. HIV-negative woman at risk for HIV. Which microbicide has been associated with a trend towards decreased HIV risk? –A) Nonoxynol-9 –B) SAVVY (C31G) –C) Cellulose Sulfate –D) Carragard –E) Buffer Gel –F) Pro 2000

21. Case 1: HIV Prevention 18 y.o. HIV-negative woman at risk for HIV. Which microbicide has been associated with a trend towards decreased HIV risk? –A) Nonoxynol-9 –B) SAVVY (C31G) –C) Cellulose Sulfate –D) Carragard –E) Buffer Gel –F) Pro 2000

22. Microbicide Product that can be applied to vaginal or rectal mucosa with the intention of preventing or significantly reducing sexually transmitted infections including HIV infection –Gel –Ring –Film

23. Possible Targets to Prevent Transmission of HIV McGowan. Biologicals. 2006

24. Pro2000 (Entry Inhibitor) 7 site study in Africa (6)/US (1) 3099 women; 20.4 months; 93.6% retention Pro2000 vs. placebo HR 0.7 (95%CI 0.5-1.1; p=0.10) Pro2000 vs. no gel HR 0.7 (95%CI 0.4- 1.0; p=0.06) Excluding time off product, Pro2000 reduced HIV incidence 36% (p=0.04) Abdool Karim CROI 2009, LB48

25. Microbicides in Clinical Trials Pro2000 study by British Microbicide Development Program –0.5% Pro2000 ongoing –2% Pro2000 arm closed by DSMB 2/2008 Microbicides containing antiretrovirals; topical Pre-Exposure Prophylaxis –Tenofovir 1% gel (HPTN 059, CAPRISA, VOICE) –TMC 120 (IPM) –UC-781 (CONRAD)

26. Case 1 Summary: HIV Prevention/Microbicides 18 y.o. HIV-seronegative woman has recently been treated for gonorrhea –ABCs and possibly other interventions such as female condom may reduce HIV risk –Early microbicide trials with non-specific agents generally not successful, but… –Recent experience with Pro2000 encouraging –Results of trials with antiretroviral-containing microbicides are eagerly anticipated

27. Case 2: Male Circumcision and the Risk of HIV Acquisition in Women An HIV-seropositive man is seeking circumcision. –Will circumcision influence the risk of HIV transmission to his wife?

28. Circumcision and HIV Transmission To Women Quinn N Engl J Med 2000

29. Circumcision of HIV-positive Men Wawer. CROI 2008, 33LB Rakai study of 124 discordant couples with uninfected female partner Female partners tested every 6 months

30. Circumcision in HIV-positive Men Reduced wound healing at 30 days compared to HIV-negative (73% vs. 83%, P<0.001) Less GUD in circumcised vs. uncircumcised arm of study (RR 0.48, 95% CI 0.3-0.8) Incidence in female partners; 14.4/100p-y in circumcised vs. 9.1/100p-y in uncircumcised (RR 1.59, 95%CI 0.7-4.3)

31. Transmission by Timing of Wound Healing and Resumption of Sex When sex resumedIntervention Arm Transmitted/N% Before complete healing5/1827.8% At or after complete healing6/639.5% Early vs. laterRR=2.92 (1.01-8.46) P=0.06

32. Case 2 Summary: Male Circumcision and Risk of HIV Acquisition in Women An HIV-seropositive man is seeking circumcision. Will circumcision influence the risk of HIV transmission to his wife? –Transmission from an HIV-positive man to an HIV-negative woman may be increased if sex is resumed before full wound healing –Condom use must be promoted, especially during the period of wound healing

33. Case 3: ART in Women 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. On Depo Provera since first post-partum visit. –What other considerations should guide our decision about the first-line ART regimen for this patient?

34. Case 3: ART in Women 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. On Depo Provera since first post-partum visit. She received single- dose nevirapine one year ago to reduce the risk of mother-to-child transmission of HIV during her first pregnancy.

35. Case 3: ART in Women 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. Started Depo Provera since first post-partum visit. She received single-dose nevirapine one year ago to reduce the risk of mother-to-child transmission of HIV during her first pregnancy. Which first-line ART regimen would you recommend: –A) Lopinavir/ritonavir + 2NRTI –B) Efavirenz or Nevirapine + 2NRTI –C) 3NRTI

36. Case 3: ART in Women 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. Started Depo Provera since first post-partum visit. She received single-dose nevirapine one year ago to reduce the risk of mother-to-child transmission of HIV during her first pregnancy. Which first-line ART regimen would you recommend: –A) Lopinavir/ritonavir + 2NRTI –B) Efavirenz or Nevirapine + 2NRTI BUT… –C) 3NRTI

37. Consider Women’s History of Receiving Single Dose Nevirapine No Yes No * If no reproductive potential Yes

38. Response to Nevirapine Containing ART after sd-NVP for PMTCT 218 women starting ART after participation in a trial of NVP vs. placebo for PMTCT –106 placebo and 112 sd-NVP women 6 months post ART initiation, virologic failure 5% in placebo vs. 18.4% in sd-NVP; p=0.002 Within 6 months of sd-NVP –Failure 0% placebo vs. 41.7% sd-NVP; p<0.001 Over 6 months after sd-NVP –Failure 7.8% placebo vs. 12% sd-NVP; p=0.39 Lockman NEJM 2007;356:135

39. Time to Virologic Failure when ART Started <6 Months Post Partum Lockman NEJM 2007;356:135

40. Time to Virologic Failure when ART Started >6 Months Post Partum Lockman NEJM 2007;356:135

41. Time to Virologic Failure when ART Started >6 Months Post Partum Lockman NEJM 2007;356:135

42. Archived Resistance after PMTCT Regimens SD NVP leads to archiving of resistant HIV in latent CD4+ cells in >8% of women 1 Use of additional drugs reduces but doesn’t eliminate development of NVP resistance 2,3 Resistance to other components of regimen –Postpartum 3TC resistance (15% of exposed women) associated with ~7-fold increased odds of 12-month virological failure in Cote d’Ivoire 3 1.Wind-Rotolo. JID 2009 2.Lehman. JAIDS 2009 3.Coffie CID 2008.

43. First-line Regimen Choice After SD Nevirapine Alive without Virologic Failure 0255075100125150 Week LPVr NVP Lockman. CROI Montreal February 2009

44. Case 3 Summary: ART In Women Consider history of sd-NVP when selecting first-line ART regimen in women –If women received sd-NVP within past 6 months, avoid all NNRTIs in first-line regimen –If women received sd-NVP >6 months prior to ART initiation, okay include NNRTI in 1 st line Recommendations evolving with emerging data Lamivudine resistance may also be an issue –Higher adherence independently associated with improved outcome regardless of regimen 1 1. Coffie CID 2008

45. UNAIDS Report 2008

46. Thank you! Next session: December 17, 2009 Listserv: itechdistlearning@u.washington.eduitechdistlearning@u.washington.edu Email: DLinfo@u.washington.edu

47. Welcome to I-TECH HIV/AIDS Clinical Seminar Series Next session: December 17, 2009 Devika Singh HIV and STIs, Part 4