Williams PL, Yildirim C, Chadwick EG, et al. - Researchers examined whether the risk of microcephaly is higher in individuals reporting in utero antiretroviral exposures based on long-term follow-up of infants and children who are HIV-exposed but uninfected. They evaluated 3,055 participants enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study from March 21, 2007, to Aug 1, 2017, and had at least one head circumference measurement. Over a median follow-up of 5·1 years (IQR 3·0–7·2), the cumulative incidence of microcephaly was 159 (5·2%, 95% CI 4·4–6·1) by Nellhaus criteria and 70 (2·3%, 1·8–2·9) by SMARTT criteria. Adjusted models revealed correlation of in utero exposure to efavirenz (4·7% exposed) with a raised risk of microcephaly by both Nellhaus standards and SMARTT criteria. Children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine exhibited these associations more pronouncedly than those including tenofovir plus emtricitabine. For darunavir exposure, they observed protective associations. They identified lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment among children who are HIV-exposed but uninfected with microcephaly than those without microcephaly. In view of these findings, they suggest considering alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women.