USA: A large U.S. cohort study has found that infants exposed in the womb to integrase strand transfer inhibitors (INSTIs)—a key class of antiretroviral medications—showed neurodevelopmental outcomes comparable to those exposed to other widely used HIV treatment regimens.The findings, published in JAMA Network Open, offer reassurance for clinicians and pregnant women with HIV as INSTIs continue to play an increasingly central role in first-line therapy.The study, led by Paige L. Williams from the Harvard T. H. Chan School of Public Health, examined whether maternal use of INSTI-based antiretroviral treatment (ART) during pregnancy affected early cognitive, language, or motor development in infants. Although INSTIs are now commonly recommended in perinatal HIV treatment guidelines, evidence on their long-term safety in infants remains limited.Researchers analyzed data from 1006 infants born between 2012 and 2023 to women with HIV across 22 U.S. academic centers. All children underwent standardized neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development (Bayley-III) at one year of age. Their mothers had initiated either INSTI-based, protease inhibitor (PI)–based, or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART regimens during pregnancy. The study led to the following notable findings:A total of 306 infants were exposed in utero to INSTI-based regimens, 473 to PI-based regimens, and 227 to NNRTI-based regimens, with more than half exposed from conception.Mean cognitive, language, and motor scores across all exposure groups were close to the population average of 100.No significant differences were observed between INSTI-exposed infants and those exposed to PI-based therapies in any developmental domain.Infants exposed to NNRTI-based regimens showed slightly higher mean scores than those exposed to INSTIs, especially when ART was initiated during pregnancy.Adjusted cognitive scores for INSTI-exposed infants remained near the expected norm, while NNRTI-exposed infants scored roughly 4–5 points higher.The authors noted that these differences, although statistically detectable, did not indicate a clinically meaningful deficit for INSTI-exposed children. Overall, the findings support the continued use of INSTIs in first-line HIV treatment for expectant mothers. The researchers noted several limitations, including the absence of an HIV-unexposed comparison group, which restricted direct comparison with the general population. They also acknowledged the possibility of residual confounding from unmeasured factors and highlighted that the lack of a Spanish-language assessment tool limited Hispanic representation. Moreover, the diversity of ART regimens used in the U.S. made it more challenging to model treatment selection accurately.Despite these constraints, the investigators concluded that the results reinforce current perinatal HIV treatment recommendations. With increasing numbers of pregnancies involving INSTI exposure, the authors emphasized the importance of continued follow-up into later childhood to monitor long-term outcomes.Reference:Williams PL, Boahene M, Mash LE, et al. Maternal Use of Integrase Strand Transfer Inhibitors During Pregnancy and Infant Neurodevelopment. JAMA Netw Open. 2025;8(11):e2545652. doi:10.1001/jamanetworkopen.2025.45652