Optimised prevention of postnatal HIV transmission in Zambia and Burkina Faso (PROMISE-EPI): a phase 3, open-label, randomised controlled trial

Background Transmission through breastfeeding accounts for more than half of the unacceptably high number of new paediatric HIV infections worldwide. We hypothesised that, in addition to maternal antiretroviral therapy (ART), extended postnatal prophylaxis with lamivudine, guided by point-of-care assays for maternal viral load, could reduce postnatal transmission. Methods We did a phase 3, open-label, randomised controlled trial at four health-care facilities in Zambia and four health-care facilities in Burkina Faso. Mothers with HIV and their breastfed infants without HIV attending the second visit of the Expanded Programme of Immunisation (EPI-2; infant age 6-8 weeks) were randomly assigned 1:1 to intervention or control groups. In the intervention group, maternal viral load was measured using Xpert HIV viral load assay at EPI-2 and at 6 months, with results provided immediately. Infants whose mothers had a viral load of 1000 copies per mL or higher were started on lamivudine syrup twice per day for 12 months or 1 month after breastfeeding discontinuation. The control group followed national guidelines for prevention of postnatal transmission of HIV. The primary outcome assessed by modified intention to treat was infant HIV infection at age 12 months, with HIV DNA point-of-care testing at 6 months and at 12 months. This trial is registered with ClinicalTrials.gov (NCT03870438). Findings Between Dec 12, 2019 and Sept 30, 2021, 34 054 mothers were screened for HIV. Among them, 1506 mothers with HIV and their infants without HIV, including 1342 mother and infant pairs from Zambia and 164 from Burkina Faso, were eligible and randomly assigned 1:1 to the intervention (n=753) or control group (n=753). At baseline, the median age of the mothers was 30<middle dot>6 years (IQR 26<middle dot>0-34<middle dot>7), 1480 (98<middle dot>4%) of 1504 were receiving ART, and 169 (11<middle dot>5%) of 1466 had a viral load >= 1000 copies/mL. There was one case of HIV transmission in the intervention group and six in the control group, resulting in a transmission incidence of 0<middle dot>19 per 100 person-years (95% CI 0<middle dot>005-1<middle dot>04) in the intervention group and 1<middle dot>16 per 100 person-years (0<middle dot>43-2<middle dot>53) in the control group, which did not reach statistical significance (p=0<middle dot>066). HIV-free survival and serious adverse events were similar in both groups. Interpretation Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination. Funding The EDCTP2 programme with the support of the UK Department of Health & Social Care. Copyright (c) 2024 Elsevier Ltd. All rights reserved.