The impact of dolutegravir on the growth of HIV-exposed uninfected infants: an observational cohort study in rural Tanzania.

Abstract

Antiretroviral treatment (ART) in pregnant and breastfeeding women living with HIV exposes their HIV-exposed uninfected (HEU) infants to drug, which might affect their outcomes. We evaluated the effects of maternal dolutegravir-based versus efavirenz-based ART and associated factors on growth outcomes in HEU children born to women living with HIV in rural Tanzania. In this observational cohort study, we used data from the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) to assess growth outcomes (up to age 18 months) of HEU children born to women living with HIV attending the Chronic Diseases Clinic of Ifakara in rural Tanzania between May 2012 and December 2024. Recommended first-line ART changed from efavirenz-based to dolutegravir-based from 2019 onwards. We included follow-up through database extraction on May 3, 2025. The primary outcomes were length-for-age and weight-for-length z-scores, defined using WHO child growth standards, and secondary outcomes included stunting and wasting, defined as >2 standard deviations below the WHO standard. We modelled continuous outcomes using linear random effects models and binary outcomes using logistic generalised estimating equations. Among 1019 infants born to 844 mothers, 491 (48%) mother-infant pairs were included in the efavirenz group and 528 (52%) in the dolutegravir group. Maternal ART was initiated before pregnancy in 569 (56%) mother-infant pairs, during pregnancy in 339 (33%), and during labour or after delivery in 111 births (11%). At delivery, median maternal age was 31 years (interquartile range 26-36) and 742 (78%) of mothers had a WHO stage I/II infection. Overall, 526 (52%) infants were male and 968 (96%) born at term. Infants had lower length and weight trajectories compared to WHO reference standards, irrespective of gender or ART regimen. In descriptive analyses, the prevalence of stunting measured at each visit over the first 18 months of life ranged between 18 and 31% in the efavirenz group and 8-26% in the dolutegravir group, possibly confounded by enrolment in later calendar years in the dolutegravir group. In adjusted models, we observed no difference in growth outcomes by ART regimen. In this large cohort-based study, we found no association between maternal ART regimen and growth of HEU infants, but growth remained below WHO reference standards. Our findings support the continued use of dolutegravir as the preferred first-line ART and emphasise the need for further research and targeted interventions to improve the health of the growing population of HIV-exposed uninfected infants. The Kilombero and Ulanga Antiretroviral Cohort has received funding from the Canton Basel-Stadt, the Swiss Tropical and Public Health Institute and the University Hospital Basel. This study was funded by the Goldschmidt-Jacobson Foundation and by the Mathieu Foundation. The Foundations were not involved in the study design, data collection, data analysis or writing of the manuscript. No other funding has been received.