Abstract
BACKGROUND: The impact on infant bone, growth, and renal health of in utero and breast milk exposure to contemporary antiretroviral treatment (ART) remains unclear. METHODS: Six hundred forty-three pregnant women with HIV in 9 countries in Africa, Asia, and the Americas were randomized to start ART with dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG + FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF between 14 and 28 weeks' gestation and continued for 50 weeks postpartum. Pairwise comparisons used 2-sample t tests of mean week 26 infant bone mineral content (BMC) assessed by dual-energy X-ray absorptiometry in a subset; mean infant z-scores for length-for-age z-score (LAZ), weight-for-age z-score (WAZ), and weight-for-length (WLZ) at 26 and 50 weeks; and mean infant creatinine and estimated creatinine clearance at birth and 26 weeks. RESULTS: Five hundred seventy-seven infants were included in the growth analysis, and 169 in the dual-energy X-ray absorptiometry analysis. Week 26 infant spine BMC was significantly lower in the EFV/FTC/TDF arm (133.5 g) than in the DTG + FTC/tenofovir alafenamide [143.4 g; mean difference (95% confidence intervals): 0.22 (0.02, 0.42) g] and DTG + FTC/TDF [137.4; mean difference (95% confidence interval): 0.20 (0.01, 0.40) g] arms. Mean LAZ and WAZ scores through week 50 were also significantly lower in the EFV/FTC/TDF versus DTG arms, but not WLZ. Infant obesity was rare (2%-4%) and similar between arms. There was no apparent by-arm difference in infant creatinine or estimated creatinine clearance through week 50 ( P -values ≥ 0.18). CONCLUSIONS: It is reassuring that maternal DTG-based ART during pregnancy and breastfeeding was associated with higher infant spine BMC, better growth, and less stunting than EFV/FTC/TDF.