Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options the suboptimal Prevention Mother Child Transmission HIV-1 (PMTCT) cascade implementation monitoring. The PROMISE-EPI study aims address latter by identifying infected mothers during an almost never-missed visit for their infant, second extended program on immunization at 6–8 weeks age (EPI-2). is divided into 3 components inclusive open-label randomized controlled trial aiming assess efficacy responsive preventive intervention compared routine based national PMTCT guidelines uninfected exposed infants. includes: a) Point care testing early diagnosis maternal viral load; b) single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if are virally unsuppressed. primary outcome HIV-transmission rate from EPI-2 12 months. targets screen 37,000 mother/infant pairs Zambia Burkina Faso identify 2000 clinical trial. design challenges faced described, including COVID-19 pandemic amended 2020 (triple-drug PrEP infants guided quarterly load). changes Zambian raised several questions equipoise options, standard care-triple-drug (control arm Zambia) versus study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Protocols.