Bone mineral content, growth, and renal health of infants with perinatal exposure to maternal dolutegravir vs efavirenz and tenofovir disoproxil fumarate vs tenofovir alafenamide: the randomized IMPAACT 2010 (VESTED) trial.

Abstract

Background: The impact on infant bone, growth, and renal health of in utero and breastmilk exposure to contemporary antiretroviral treatment (ART) remains unclear.

Methods: 643 pregnant women with HIV in nine 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 14-28 weeks' gestation and continued for 50 weeks postpartum. Pairwise comparisons used two-sample t-tests of mean week 26 infant bone mineral content (BMC) assessed by dual-energy X-ray absorptiometry (DXA) in a subset; mean infant z-scores for length-for-age (LAZ), weight-for-age (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: 577 infants were included in the growth analysis, and 169 in the DXA analysis. Week 26 infant spine BMC was significantly lower in the EFV/FTC/TDF arm (133.5g) compared to the DTG+FTC/TAF (143.4g; mean difference [95% CI]: 0.22 [0.02, 0.42] g) and DTG+FTC/TDF (137.4; mean difference [95%CI]: 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).

Conclusion: It is reassuring that maternal DTG-based ART during pregnancy and breastfeeding was associated with higher infant spine bone mineral content, better growth, and less stunting than EFV/FTC/TDF.