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WGHA Discovery Series: Cathering Wilfert

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Washington Global Health Alliance Discovery Series …

Washington Global Health Alliance Discovery Series

Catherine Wilfert, MD [
December 1, 2008
'Global Prevention of Mother to Child Transmission of HIV-1'

Published in: Education, Health & Medicine

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    • 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
    • 2. EGPAF International Family AIDS Initiatives
      • Acknowledges all of the host countries for supporting this work
      • Thank all of our staff in the US and in country
      • Thank all the people we serve
      • Pictures were taken with permission and do not imply anything about serostatus of persons
    • 3. The Devil is in the Details
      • Brief overview of PMTCT
      • EGPAF PMTCT
      • Breast Feeding
      • Treatment of Moms
      • Care & Treatment especially infants
      • Prevention & prevalence
    • 4.  
    • 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
    • 7.  
    • 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
    • 9.  
    • 10.
      • Family-Centered HIV/AIDS Prevention and Treatment Programs
      • ______________________________________________________
        • HIV prevention services
        • for pregnant women and infants
        • Treatment and care services
        • for children and families
      • Program Model
        • • Partner with host governments
        • • De-centralized community focus
        • • Training and technical assistance
        • • Capacity building for sustainability
        • • Program monitoring & evaluation
        • • Infrastructure and logistics development
    • 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
    • 15.  
    • 16. EGPAF Africa: Women Reported to Receive Prophylaxis for PMTCT
    • 17. Number Trends With Time
    • 18. Percent Uptake With Time
    • 19.  
    • 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
    • 24.  
    • 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
    • 28.  
    • 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
    • 32.  
    • 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
    • 36.  
    • 37. HIV + Women, Reported Access to Care and Treatment Services
    • 38.
      • Care and Treatment : EGPAF Impact
      • _______________________________
        • • HIV/AIDS Care and Support
        • More than 470,000 people enrolled,
        • including over 39,000 children
        • • HIV/AIDS treatment (2008)
        • More than 220,000 people treated,
        • including over 30,000 children
    • 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
    • 42. Cher Study; NEJM 359:2241
      • After diagnosis 9 infants died or had disease progression prior to screening
      • During screening 122/532 (23%) required therapy (CD4 < 25%, symptomatic) or died
      • Median age 7.4 weeks for randomization to treatment or deferred treatment of 377 infants
      • By 40 weeks of evaluation 66% of infants in deferred treatment group needed ARV
      • Early treatment reduced early infant mortality by 76% and HIV progression by 75%
    • 43.  
    • 44. HIV Exposed Infants: Number Reported At Regular Well Child Visits 66,009 * 80,967 * 117,788 * * Number of HIV Exposed Infants
    • 45. PMTCT In Low Prevalence Settings
      • The program needs to accrue additional benefits besides HIV infections averted
      • HIV free survival of infants is first step
      • Lower morbidity of diseases that can be identified and averted/treated in ANC and postnatal care is second step
      • Decreased maternal mortality
    • 46.  
    • 47. Total Cost of PMTCT Program
    • 48. HIV Infections Averted
    • 49.  
    • 50. Cost per Infection Averted
    • 51. Cost per Woman Served
    • 52.  
    • 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
    • 57.  
    • 58.