2012 International AIDS Conference, Washington DC, July 22-27)

1. Draft Generic Protocol:Measuring Impact and Effectivenessof National Programs for Prevention of Mother-To-Child HIV Transmission at Population-Level Using a Facility-Based ApproachThu-Ha Dinh, MD, MS (CDC – Atlanta)Nathan Shaffer, Nigel Rollins, Chika Hayashi (WHO) 2012 International AIDS Conference, Washington DC, July 22-27) Center for Global Health Division of Global HIV/AIDS

2. Overview of Presentation • Case definitions • Key definitions • Generic protocol (summary) • Examples • Discussions

3. Case Definitions • HIV-exposed infant - An infant whose • Blood sample (Dried Blood Spot [DBS] prefered)is positive with an HIV antibody test • and/or mother is HIV-infected • HIV-infected child– A child • (<18 mths of age) whose DBS sample is positive with An HIV antibody test AND an HIV DNA PCR test • (≥18 mths of age) whose blood sample is positive with two/three different HIV antibody tests

4. Key definitions Perinatal MTCT rate (Early transmission rate) • Proportion of HIV-exposed infants at birth identified as HIV-infected at 4-8 weeks of age Extended postpartum MTCT rate (Late transmission rate) • Proportion of HIV-exposed infants at birth who acquire HIV-infection after the perinatal period (testing negative at 4-8 wks and positive later postpartum) Overall MTCT rate (Final transmission rate) • Proportion of HIV-exposed infants at birth who acquire HIV-infection cumulatively from perinatal period to the end of breastfeeding; typically assessed at 12-24 months postpartum

5. Key definitions Population-based level • Survey sample is representative for ≥ 80% of ALL INFANTS • Participating in PMTCT program is NOT one of inclusion criteria  ≥ 80% ALLHIV-exposed infants in your country • WHERE SHOULD WE RECRUITE PARTICIPANTS? • (1stimmunization? 6wk postnatal care? 1st HIV PCR EID?) • Selected routine service  the survey’s enrolment site

6. Survey objectives Primary objective. To monitor impact and effectiveness of national PMTCT program on overall (final) MTCT rate measured at xx months of age • Perinatal (early) measured at 4-8 weeks postpartum • Extended postnatal (late) MTCT measured at xx months of age xx months = duration of breastfeeding practice in country (12 months to 24 months)

7. Survey design (final MTCT rate) Baseline. Cross sectional to recruit eligible caregiver-infants ( 4 to 8 wks postpartum) Perinatal (early) MTCT rate Follow-up (prospective cohort) exposed AND un-infected infants Extended postnatal MTCT rate At scheduled follow-up visits < 18 months • Scheduled visits every 3 or 6 months • Interview caregivers • Child’s blood samples for HIV testing infected children • Mortality • Loss to follow-up* At scheduled xx mth (18-24) follow-up visit • Interview caregivers • Child’s blood samples for HIV testing infected children

8. Methods • Sampling: Multi stage sampling methods  national and provincial estimates • ## blood samples of eligible caregiver-infant pairs enrolled • ## (20%) of total facilities in all ## provinces • Interview data collection:  real time/web-base data collection • Laboratory: -- Testing strategy -- Test kits -- Where HIV tests will be done

9. Methods: Sample Size • Effective sample size (HIV-exposed infants) • Estimate expected perinatal/early (baseline) and extended postnatal (last FLU visit) MTCT rates • Determine desired precision of estimate • Final sample size (all infants) • % of loss to follow-up, refusal at each survey visit • HIV prevalence among pregnant women (1st ANC + acquisition) • Sampling frame (all infants) Work with a statistician to develop a feasible sample size

10. Potential Nested Studies • Maternal seroconversion/incidence postpartum, during breastfeeding • Drug resistance (leftover DBS) • Treatment outcome of HIV-infected infants • Maternal retention and linkages with ART care and treatment • Immunization coverage/uptake (measles - leftover DBS) These need to be reviewed carefully in terms of capacity and resources

11. Examples (South Africa) Enrollment site: primary health care facility (PHC) Eligible criteria at enrolment: all 4-8 infants attending selected PHC for the 1st immunization Case definitions • HIV-exposed infant - An 4-8 week old infant whose Dried Blood Spot (DBS) sample is positive with an HIV ELISA • HIV-infected infant - An infant whose DBS sample is positive with an HIV ELISA test AND an HIV DNA PCR

12. Examples (Zimbabwe) Enrollment site: primary health care facility (PHC) Eligible criteria at enrolment: • all 4-12 infants (stratified, 4-8 and >8 to 12wks) • attending selected PHC for for the 1st immunization and 6 wks postnatal care Case definitions • HIV-exposed infant - An 4-12 week old infant whose Dried Blood Spot (DBS) sample is positive with an HIV ELISA • HIV-infected infant - An infant whose DBS sample is positive with an HIV ELISA test AND an HIV DNA PCR

13. Examples (Rwanda) Enrollment site: primary health care facility (PHC) Eligible criteria at enrolment: • all 6-10 infants (6-8 and >8 to 10wks) • attending selected PHC for for the 1st immunization Case definitions – • HIV-exposed infant - An 6-10 week old infant • whose mother is HIV+ • If mother’s not available -> infant-DBS sample is positive with an HIV ELISA • HIV-infected infant - An exposed infant whose DBS sample is positive with an HIV DNA PCR

14. Potential Uses - Applications • To monitor progress of elimination of MTCT, HIV-free survival and new pediatric HIV infections among children <2 years of age • To assess PMTCT program coverage and quality of interventions along the continuum • To validate ANC sentinel surveillance  estimate HIV acquisitions during pregnancy

15. Discussions: Can we adapt the protocol for my country? • YES!!  • Coverage of the selected routine service ≥ 80% • EID service is available in country • Have capacity and resources • CONSIDERABLE !! • Coverage of the selected routine service ≥ 70% • Need an additional assessment to explore what happened to another 10% less • HIV prevalence among ANC attendees <5% • Consider recruiting survey population at EID site (if coverag≥80%) • Funding

16. Discussions Do we have to adapt the full protocol? NO  • First step (Year 1) • Adapt the baseline component  Early (Perinatal) MTCT rate – • Second step (Year 2) • Adapt the full protocol when funding and having capacity to do the follow-up

17. Discussions How often should we conduct the survey? • Repeat every year -> trend and identify gaps to improve the program • Repeat every 2, 3, or 5 years when the program is stable, and fully functional • One-time • Good enough  get some ideas of where the program is to identify gaps, and set realistic targets for the national PMTCT program

18. Acknowledgments • Survey team in KZN province in South Africa • Piloted in 3 districts (2008) then KZN province (2009) • National PMTCTE survey in South Africa • 2010: Piloted the 1st national perinatal MTCT) • 2011: Piloted the follow-up component • Investigators from Kenya, Rwanda, Swaziland, Zambia, and others (consultation meeting Jul’s 2009) • Field experiences: Malawi, Namibia, Nigeria, Mozambique, Zimbabwe and others • PEPFAR/CDC, WHO, UNICEF and IATT members The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the centers for Disease control and Prevention