A systematic review of the use of antiretroviral drugs to prevent HIV in neonates and infants

Abstract Background Preventing the postnatal transmission of HIV remains an unfinished goal globally. Infant antiretroviral prophylaxis remains important, particularly when maternal viral suppression is not assured. We conducted a systematic review to identify optimal infant antiretroviral prophylaxis to inform World Health Organization 2025 guidelines. Methods PubMed, Embase, and Global Index Medicus were searched for randomized controlled trials published in 2014–2024 evaluating antiretrovirals given to infants to prevent postnatal HIV transmission. Eligible articles from prior systematic reviews from 1994–2014 were also reviewed. Two risk periods were considered: (i) the early postnatal period from delivery to six weeks of age, and (ii) during breastfeeding from six weeks to 12 months. Scenarios were defined as higher risk when the mother was not on ART and lower risk when mothers were on ART. Results We screened 1,670 studies and reviewed 70 full-text articles. Nine trials (16,279 infants) met eligibility criteria. In five studies addressing high-risk scenarios in the early postnatal period, use of three drugs for infant prophylaxis for one week followed by a single drug through six weeks resulted in 0.1% HIV transmission risk; two drugs through six weeks resulted in 1.5% risk; and one drug alone through six weeks, 2.5-8.2% risk. In six studies addressing higher-risk scenarios during breastfeeding, single-drug prophylaxis throughout breastfeeding resulted in <1%–1.5% transmission risk at 12 months. No studies evaluated infant prophylaxis in lower-risk early postnatal scenarios. In low-risk breastfeeding scenarios, six weeks of infant prophylaxis resulted in <1% risk at 12 months. Conclusion In higher-risk scenarios, trial data show infants have the lowest risk of HIV transmission during the early postnatal period when they receive two weeks of three antiretroviral drugs followed by a single drug through six weeks. Afterwards, single-drug prophylaxis throughout breastfeeding demonstrates the lowest transmission risk at 12 months.