Bone Mineral Content, Growth, and Renal Health of Infants With Perinatal Exposure to Maternal Dolutegravir Versus Efavirenz and Tenofovir Disoproxil Fumarate Versus Tenofovir Alafenamide: The Randomized IMPAACT 2010 (VESTED) Trial.

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.