WGHA Discovery Series: Cathering Wilfert

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

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

The Devil is in the Details

Brief overview of PMTCT

EGPAF PMTCT

Breast Feeding

Treatment of Moms

Care & Treatment especially infants

Prevention & prevalence

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

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

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

Family-Centered HIV/AIDS Prevention and Treatment Programs

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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

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

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

Cumulative PMTCT Cascade All Countries 2000-2008

Cumulative PMTCT Cascade: Africa 2000-2008

EGPAF Africa: Women Reported to Receive Prophylaxis for PMTCT

Number Trends With Time

Percent Uptake With Time

Swaziland Cumulative PMTCT Cascade

Uganda Cumulative PMTCT Cascade

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%)

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

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%

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

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

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

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

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

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

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)

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

HIV + Women, Reported Access to Care and Treatment Services

Care and Treatment : EGPAF Impact

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• 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

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

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

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

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%

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

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

Total Cost of PMTCT Program

HIV Infections Averted

Cost per Infection Averted

Cost per Woman Served

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

Uncorrected Seroprevalence Reported in ANC

Yearly Seroprevalence

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