Implementation of an upgraded strategy to reach zero HIV transmission by breastfeeding in rural and urban settings in Zambia – the PROMISE-ZERO study

ongoing

Most cases of paediatric HIV now occur during the breastfeeding period. Through an EDCTP-2 funded randomized controlled trial in Burkina Faso and Lusaka, we tested a postnatal prevention strategy relying on point of care (POC) early infant diagnosis (EID) and maternal VL tests for same-day infant lamivudine initiation when VL>1000 copies/mL until the end of breastfeeding, and maternal ART optimization. At the 2nd immunization visit (EPI-2), maternal HIV status was reassessed and infants from HIV-positive mothers were enrolled. Among the 754 children in each arm, the 12-month transmission rate was 1.16/100pers-yrs (CI:0.44-2.60) in the control arm vs. 0 (97.5%CI: 0.71) in the intervention arm. The period at risk for infant (i.e.HIV VL>1000c/mL and no prophylaxis) was 5.96/100pers-days (95%CI: 5.85-6.1) vs. 0.36 (95%CI: 0.34-0.36). The primary objective of the proposal is to assess the effectiveness of a similar intervention in 2 provinces of Zambia, to reach zero postnatal transmission. For this implementation research proposal, we will use the RE-AIM framework. We designed a cluster randomized controlled arm with 2000 HIV-exposed HIV-negative children (1000 per arm) recruited at EPI-2 visit, in 40 clusters (maternal & child health centres) matched for district and size. The primary trial outcome is postnatal HIV infection at 18 months. The EID and VL tests will be organised at the district level with a mobile team equipped with POC machines, and one referral MCH centre equipped with Xpert platform. Research capacity will be built through PhD fellowships. By demonstrating the (cost)-effectiveness of POC tests and infant lamivudine (health technologies) to prevent infant HIV infection, identifying and addressing barriers to uptake in RE-AIM, notably via end-users participation, and ensuring the translation of research findings into policy through the strong involvement of policy makers, this study addresses both objectives of EDCTP-3 and those of the present call.