Draft Generic Protocol: Measuring Impact and Effectiveness of National Programs for Prevention of Mother-To-Child HIV Transmission at Population-Level Using a Facility-Based Approach Thu-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

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

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

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 months postpartum

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% ALL HIV-exposed infants in your country WHERE SHOULD WE RECRUITE PARTICIPANTS? (1 st immunization? 6wk postnatal care? 1 st HIV PCR EID?) Selected routine service  the survey’s enrolment site

Survey objectives Primary objective. To monitor impact and effectiveness of national PMTCT program on overall (final) MTCT rate measured at xx months of age 1.Perinatal (early) measured at 4-8 weeks postpartum 2.Extended postnatal (late) MTCT measured at xx months of age xx months = duration of breastfeeding practice in country (12 months to 24 months)

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

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

Methods: Sample Size Work with a statistician to develop a feasible 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 (1 st ANC + acquisition) Sampling frame (all infants)

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

Examples (South Africa) Enrollment site: primary health care facility (PHC) Eligible criteria at enrolment: all 4-8 infants attending selected PHC for the 1 st 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

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 1 st 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

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 1 st 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

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

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

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

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

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 1 st 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