Draft Generic Protocol:

Measuring Impact and Effectivenessof 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 HealthDivision 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 definitionsPerinatal 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

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?

(1st immunization? 6wk postnatal care? 1st 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 postpartum2. 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

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 estimateFinal 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)

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 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

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

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

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 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