Washington Global Health Alliance Discovery Series Catherine Wilfert, MD [ December 1, 2008 'Global Prevention of Mother to Child Transmission of HIV-1'

1. Global Prevention of Prevention of Mother to Child transmission of HIV-1 The Devil is in the Details Catherine M Wilfert MD Dec 1, 2008

5. Biological Factors affecting Perinatal Transmission of HIV Maternal Placental Fetal Duration of Ruptured Membranes Breast Feeding T.Quinn HIV-1 RNA ART Prx C-Section ART Prx

6. HIV Mother-To-Child Transmission Rates without ARV with 18-24 months BF Derived From 3 Controlled Clinical Trials

8. Access to Mother-to-Child Prevention WHO, UNAIDS, UNICEF - Towards Universal Access: Progress Report 2008 67% of pregnant women not receiving PMTCT drugs 80% of HIV-exposed infants not receiving PMTCT drugs

11. EGPAF Country Programs 2000 8 sites in 6 countries 2008 >3000 sites in 17 countries South Africa Rwanda Uganda Kenya Thailand Angola D.R. Congo Malawi Tanzania Zambia Zimbabwe Russia Swaziland Dominican Republic Cameroon India Georgia Honduras Mozambique Cote d’Ivoire China

12. HIV Prevention : EGPAF Impact ______________________________________________________________ • More than 6.2 million pregnant women reached to date with services to prevent transmission to their babies (PMTCT) • 2007 EGPAF programs accounted for 28% of global PMTCT treatments • 2008 will reach more than 1.7 million women in 17 countries • Continuous service refinement and performance improvement

13. Cumulative PMTCT Cascade All Countries 2000-2008

14. Cumulative PMTCT Cascade: Africa 2000-2008

16. EGPAF Africa: Women Reported to Receive Prophylaxis for PMTCT

17. Number Trends With Time

18. Percent Uptake With Time

20. Swaziland Cumulative PMTCT Cascade

21. Uganda Cumulative PMTCT Cascade

22. Reported Supervised Delivery Rates in All Countries First ANC = 2,864,694 Deliveries = 1,798,949 (61%) # HIV + = 179,078 # HIV+ del = 89,761(52%) # on Rx = 10,401 # del on Rx = 8120(78%)

23. Breastfeeding Postnatal Transmission: Accounts for at Least One-Third of all Transmissions Among Breastfeeding Women MG Fowler 0% 20% 40% 60% 80% 100% Early Antenatal (<36 wks) Late Antenatal (36 wks to labor) Labor and Delivery Late Postpartum (6-24 months) Early Postpartum (0-6 months) Proportion of infections

25. Breastfeeding + 6 Months AZT (then Weaning) Did Not Reduce MTCT Rates to Those in Formula Fed Infants Thior I et al. JAMA 2006;296:794-805 Formula Breastfeeding + AZT P=0.02 Infection btn birth - 7 months was 5.7% Infection btn birth-7 months was 1.8%

26. Mashi: Cumulative Rate of Death by Infant Feeding Thior I et al. JAMA 2006;296:794-805 Formula Breastfeeding + AZT overall p=0.21 7 month difference Significantly More Early Deaths With Formula Feeding p=0.003

27. Cumulative Rate of HIV Infection or Death by Infant Feeding Thior I et al. JAMA 2006;296:794-805 Formula Breastfeeding + AZT P=0.48 Resulting in No Difference in HIV-Free Survival

29. SWEN: 6-Week NVP Reduces Risk of HIV Infection or Death at Age 6 Wks and 6 Mos RR 0.58, p=0.008 RR 0.73, p=0.028

30. SWEN: Visit-Specific Breastfeeding Frequencies: Decreases from 73% at 14 wks to 31-32% at 6 mos

31. Probability of HIV-1 Infection or Death in Infants Uninfected at Birth by Treatment Arm: PEPI-Malawi Age 1 wk 6 wks 9 wks 14 wks 6 mos 9 mos 12 mos 15 mos 18 mos 24 mos Estimates (%) Control 0.6 6.7 9.3 10.7 13.2 16.8 18.1 20.5 22.6 24.1 Extended NVP 0.6 3.3 4.2 4.7 6.6 10.6 13.9 16.0 19.0 20.9 Extended NVP+ZDV 0.5 2.8 4.1 5.1 8.2 11.2 15.0 16.5 18.6 22.0

33. PEPI-Malawi: Visit-Specific Breastfeeding Frequencies Among HIV Uninfected Infants at Prior Visit Decreases from 89-91% at 6 mos to 22-25% at 9 mos

34. Stopped breastfeeding Continued breastfeeding No Overall Benefit in HIV-Free Survival to Early Cessation vs. Continued Breastfeeding Thea D et al. 14 th CROI, 2007, Los Angeles, CA Abs. LB p = 0.21 Overall HIV-free Survival among Children without HIV & Still Breastfeeding at Age 4 Months of Age by Group Assignment (Abrupt vs Standard Weaning)

35. Breastfeeding Women With Low CD4 Are at Most Risk of Infecting Their Infants: Zimbabwe Iliff PJ et al. AIDS 2005;19:699-708 Postnatal HIV Infection from Age 6 Weeks - 18 Months (N=2,055) Women Who Would be Eligible for HAART

37. HIV + Women, Reported Access to Care and Treatment Services

39. 2 year Mortality (Zvitambo ) Marinda et al. Ped Inf Dis J 2007;26:519-26 NE - not exposed; NI - HIV-exposed uninfected; PN - postnatal, IP - intrapartum; IU - in utero HIV status 9510 3135 381 508 258

40. M Project HEART (EGPAF): Percentage Distribution of Children Ever on ART at the End of Sept 2008

41. Cher Study: Time to Death (NEJM 359:2233,2008) Time to Death (months) Failure Probability Arm 1 Arm 2 & 3 Patients at risk P = 0.0002 Early Treatment 0.00 0.20 0.40 0.60 0.80 1.00 0 3 6 9 12 70 137 184 241 252 Arm 2 & Arm 3 32 56 85 112 125 Arm 1 Month 12 Month 9 Month 6 Month 3 Month 0

44. HIV Exposed Infants: Number Reported At Regular Well Child Visits 66,009 * 80,967 * 117,788 * * Number of HIV Exposed Infants

47. Total Cost of PMTCT Program

48. HIV Infections Averted

50. Cost per Infection Averted

51. Cost per Woman Served

53. Four Intervention Opportunities YEARS Treatment Of HIV INFECTED Adapted from: Cohen et al, JCI, 2008 Cohen IAS 2008 YEARS Seronegative Exposure Unknown Behavioral, Structural Circumcision Condoms Behavior Change Hours/Months ART PrEP EXPOSED Predelivery Delivery 72h ART PEP Vaccines EXPOSED Postdelivery

54. Uncorrected Seroprevalence Reported in ANC

55. Yearly Seroprevalence

56. Decline in Seroprevalence Among Women Accessing PMTCT Services in Selected Countries Submitted to AIDS, ,Agbessi et al