JAMA Netw Open. 2025 Nov 3;8(11):e2545652. doi: 10.1001/jamanetworkopen.2025.45652.
ABSTRACT
IMPORTANCE: Current perinatal HIV treatment guidelines recommend inclusion of integrase strand transfer inhibitors (INSTIs), but few studies have evaluated the safety of INSTIs for infant neurodevelopment.
OBJECTIVE: To compare the neurodevelopment of infants born between 2012 and 2023 with in utero exposure to INSTI-containing antiretroviral treatment (ART) regimens with that of infants exposed to protease inhibitor (PI)-containing or nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted in 22 US-based academic research centers among women with HIV and their uninfected infants born between January 1, 2012, and December 31, 2023, and exposed in utero to INSTI-based, PI-based, or NNRTI-based combination ART regimens. The children underwent neurodevelopmental assessments at 1 year of age. Data were analyzed between January 13 and September 5, 2025.
EXPOSURE: Initial maternal ART regimen during pregnancy.
MAIN OUTCOMES AND MEASURES: Neuropsychologists administered the Bayley Scales of Infant and Toddler Development-3rd Edition (Bayley-III) to children at 1 year of age. Mean differences by drug class were calculated for Bayley-III cognitive, language, and motor development domain scores, adjusting for confounders. Stratified analyses were conducted by timing of maternal ART initiation.
RESULTS: A total of 1006 infants born between 2012 and 2023 with a Bayley-III assessment at 1 year of age were included. The mean (SD) maternal age at delivery was 30.3 (6.0) years; 663 mothers (65.9%) had an annual income of less than $20 000; and 125 (12.4%) had perinatally acquired HIV. Of the 1006 infants, 306 were exposed in utero to an initial INSTI-based maternal ART regimen, 473 to a PI-based regimen, and 227 to an NNRTI-based regimen; 531 (52.8%) were exposed from conception. Overall, mean (SD) scores for cognitive (101.7 [14.2]), language (95.5 [13.8]), and motor development (96.4 [13.2]) domains were near reference standards (100 [15]). There was no difference in Bayley-III cognitive, language, or motor development domain scores between those exposed to INSTI-based vs PI-based regimens. However, INSTI-exposed infants had slightly lower mean scores than infants exposed to NNRTI-based regimens for cognitive (adjusted mean difference, -2.94; 95% CI, -5.47 to -0.41), language (adjusted mean difference, -1.96; 95% CI, -4.50 to 0.57), and motor development (adjusted mean difference, -1.60; 95% CI, -4.15 to 0.94) domains, with larger differences among infants whose mothers initiated ART during pregnancy.
CONCLUSIONS AND RELEVANCE: In this cohort study, infants exposed in utero to INSTI-based ART regimens had mean neurodevelopmental scores similar to those for infants exposed to PI-based regimens but lower than those for infants exposed to NNRTI-based regimens, particularly when their mothers initiated ART after conception. Notably, adjusted mean cognitive domain scores for INSTI-exposed infants were close to the expected population mean of 100, while NNRTI-exposed infants scored 4 to 5 points above the population mean. These findings support continued inclusion of INSTIs in first-line regimens for pregnant women with HIV.
PMID:41296482 | DOI:10.1001/jamanetworkopen.2025.45652
