1. Cascade of Prevention of Mother-to-Child Transmission of HIV (PMTCT) for Option B+ Transition: Findings from a Cohort of a Nationally Representative Sample of Mother-Infant Pairs, Zimbabwe, 2013-2014 Dr Angela Mushavi National PMTCT and Pediatric HIV Care and Treatment Coordinator MOHCC, Zimbabwe ICASA 2015 3/12/2015

2. Principal Investigators -Owen Mugurungi - MD -Lead Principal Investigator Angela Mushavi- MD Prof. Mufuta Tshimanga- MD Peter Kilmarx – MD Thu-Ha Dinh- MD, MS Other team members 1.Ministry of Health and Child Welfare in Zimbabwe 2.Centers for Disease Control and Prevention 3.Division of Community Medicine 4.National microbiology reference laboratory 5.Provincial Department of Health Technical Advisors: PEPFAR-Zimbabwe- UNICEF-WHO-EGPAF-PPF Study team

3. Zimbabwe and PMTCT Program Adult HIV prevalence 15% 2010: Adopted WHO PMTCT Option A Mother: ART for life if CD4 ≤350 or AZT in ANC and single-dose nevirapine (sdNVP) at onset of labor if CD4>350 Infant: Daily nevirapine (NVP) throughout duration of breastfeeding 2014: Transitioned to Option B+: ART for life regardless of CD4

4. Goal Survey conducted to monitor the effectiveness of the Zimbabwean National PMTCT programme on HIV-free survival among HIV-exposed infants from 6 weeks until 18 months postpartum

5. Primary objectives To determine the overall national population-based MTCT rate To determine the national population-based HIV-free survival rate

6. Secondary objectives To assess coverage of key PMTCT interventions along the PMTCT cascade To identify probable/confirmed maternal HIV acquisition during pregnancy To assess ARV adherence in infants and mothers To describe infant feeding patterns

7. From ~1,500 primary health care clinics/district hospitals/mission hospitals providing child immunization were stratified into 3 strata by province (10 provinces) 151 clinics were randomly selected within each stratum

8. Sampling A multi-stage stratified sampling probability proportional to size (PPS), stratified and systematic sampling design used to select a representative national sample of caregiver-infants aged 4-12 weeks

9. Methods: Design 1.Baseline component: Feb-August 2013 –Cross-sectional to select a nationally representative sample of mother-infant pairs (aged 4-12 weeks) –Recruitment time: 6 weeks at each facility 2. Follow-up component : March 2013 to Dec 2014 –Prospective cohort of HIV-exposed infant-mother pairs –Visits scheduled at 3-6–9–12-15 and 18 months –Location: the same facility where the HIV- exposed infants were recruited at baseline

10. Case Definitions HIV-positive mother – Who reported having an HIV-positive status during pregnancy and the status was documented in her ANC card or her child health card; OR – Her child DBS was positive with an ELISA test HIV-exposed infant – Infant born to an HIV-positive mother; OR – Infant’s DBS (iDBS) positive with one ELISA test An HIV-infected infant – iDBS positive with an HIV DNA PCR test

11. Methods: Inclusion/Exclusion Inclusion criteria Baseline Infants aged 4-12 weeks and mothers/caregivers attending the selected (studied) clinics Follow-up HIV exposed infants who are enrolled at the baseline Exclusion criteria for both components Severely ill infants needing emergency medical care or urgent referral to the next level of care

12. GENERAL APPROACH AND CONCEPTUAL FRAMEWORK Survey design: an 18 month prospective cohort Baseline: at the 1 st immunization clinic Follow-up: HIV exposed infant Survey question. Cascade and Effectiveness of the national PMTCT program HIV-exposed AND un-infected infants Enrol consenting mother-baby pairs for the follow-up component - Interview Schedule a next follow up visit HIV-unexposed infants HIV-infected

13. Study Profile at Baseline

14. Objective: For this abstract We reconstructed PMTCT cascade from antenatal care (ANC) to 18 months post- delivery

15. Analysis Retrospective and prospective cohort analysis used to do: Descriptive analysis Kaplan-Meier analysis to estimate MTCT rate and infant mortality (survival rate) among HIV-exposed infants from 6 weeks to 18 months of age Estimates were adjusted for clustering, nonresponse, and weighted for number of infants aged 4-12 weeks receiving 1 st immunization/annually

16. Main Findings– Update from Abstract 1. Program implementation: Cascade 2. Outcome/Effectiveness of the program

17. Characteristic of Mothers at Baseline by Maternal HIV-Status HIV-negative mothers HIV-positive mothers (20.5%) Weighted %95%CIWeighted %95%CI Relationship with child Mother99.8[99.4-99.9]99.5[99.0-99.8] Maternal age (mean)25.428.5 < 20 yrs of age20.0[17.5-20.5]6.1[5.0-7.4] Marital status Single5.4[4.5-6.5]9.9[7.9-12.3] Married93.7[92.6-94.7]87.3[84.6-89.5] Widowed0.8[0.6-1.1]2.8[1.8-4.5] Mother's highest education None1.3[0.9-1.9]1.8[1.0-2.9] Grades 1-729.4[26.0-33.1]34.2[30.8-37.8] Grades 8-1265.8[62.0-69.4]61.1[57.3-64.7] Tertiary/tech/uni3.4[2.5-4.6]2.8[1.8-4.4]

18. Obstetric History of Mothers at Baseline by Maternal HIV Status HIV-negative mothersHIV-positive mothers (20.5%) Weighted %95%CIWeighted %95%CI No. of live children (including the recent infant) 135.0[33.6-36.5]20.3[17.9-22.9] 227.3[25.8-28.9]27.3[24.7-30.1] 318.5[17.4-19.7]24.6[22.2-27.1] ≥ 419.1[17.6-20.7]27.9[25.0-30.9] Planned pregnancy ? Yes74.3[71.6-76.8]58.7[54.8-62.5] No25.7[23.2-28.3]41.2[37.4-45.1] Attend ANC? Yes95.2[93.8-96.3]94.6[92.3-96.2] No4.8[3.7-6.2]5.4[3.8-7.7]

19. Characteristic of Infants at Baseline by Maternal HIV-Status HIV-negative mothers HIV-positive mothers (20.5%) Weighted %95%CIWeighted %95%CI Gestational age: 1st ANC visit <=24 weeks69.4[66.3-72.3]70.8[66.8-74.5] 25-35 weeks27.9[25.1-30.8]27.2[23.5-31.2] >=36 weeks2.7[2.1-3.5]2.1[1.1-3.7] Mode of delivery Vaginal delivery94.8[94.0-95.5]94.3[92.4-95.8] Assisted Delivery4.6[4.0-5.3]5.5[4.0-7.4] Caesarean section0.4[0.2-0.7]0.2[0.0-0.7] Infant's birth weight <2.5 kg7.6[6.6-8.7]11.9[9.9-14.3] >=2.5 kg92.4[91.3-93.4]88.1[85.7-90.1] Feeding practices Exclusive breast-feeding62.2[57.1-67.1]70.0[66.0-73.7] Mixed breast-feeding37.7[32.9-42.8]27.8[23.9-32.1] No breast-feeding0.1[0.0-0.2]2.2[1.5-3.3]

20. HIV testing Services for Pregnant Women HIV-negative mothers HIV-positive mothers (20.5%) Weighted %95%CIWeighted %95%CI Being tested No2.61.9 – 3.26.84.4 – 9.2 Yes97.496.7 – 98.193.290.1 – 95.6 Knowing test result No0.20.1 – 0.30.90.1 – 1.6 Yes99.899.6 – 99.499.198.4 – 99.9 #of ANC visit (mean, median, range)4.2 ; 3.6; 1-204.3; 3.7, 1-12

21. Weighted HIV Prevalence by timing of HIV infection among Women during Pregnancy Overall HIV prevalence 20.5% (95%CI 18.8 - 22.2)

22. Transition from Option A to Option B+ (Cumulative ART Initiation for HIV-positive Mother

23. Breastfeeding practice in HIV-Positive Mothers Duration of breast-feeding: Average of breastfeeding: 11.8 months, Range: 1 - 19.4 months

24. Cumulative Mother to Child Transmission Rate Rate6W (early)6M (late)12M (late)18M (late) HIV+3.6%5.3%6.6%7.0%

25. Discussions Global cascade target by 2020 95% of women tested during ANC 95% of women who tested for HIV knowing their test results 90% of HIV infected women on ART MTCT rate goals by 2015 and 2020 2% measured at 6 weeks 5% measured at 18 months Zimbabwe cascade achieved 95% of women were tested during ANC 99.5% of women who tested for HIV knowing their test results 73.4%-83.7% of HIV infected women on ART Zimbabwe MTCT rates achieved 3.6% measured at 6 weeks 7.0% measured at 18 months

26. Recommendations Reinforce quality implementation of Option B+ To reduce further MTCT rate Early ART as soon as tested HIV positive –with good SCMS Advocate for early ANC visit – before 12 weeks. Re-test previously HIV-negative or unknown status at 6 weeks postnatal visit or 1 st immunization to detect incident HIV infection Exclusive breast-feeding during the first 6 months and Continue breastfeeding to 24 months to reduce mortality

27. Thank you!!