Information is limited about the impact of specific maternal antiretroviral treatment (ART) regimens during pregnancy and breastfeeding on infant growth. Stunting in infancy impacts cognitive development and adult height. We compared infant growth at ~26 and ~50 weeks of age by maternal regimen in a post hoc analysis of the IMPAACT 2010 randomized trial which evaluated three ART regimens in pregnancy.
Pregnant women with HIV in 9 countries were randomized 1:1:1 to start open-label maternal ART with dolutegravir (DTG) plus emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF at 14-28 weeks’ gestation. Mothers and infants were followed through Week 50 postpartum; infant length and weight were measured using standardized procedures. We calculated Z-scores for length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WHZ) using WHO standards. Pairwise comparisons of mean LAZ, WAZ, and WHZ used two-sample t-tests at ~26 and ~50 weeks of age. The proportion of infants in each arm with severe stunting (LAZ below -2) was estimated.
In predominantly breastfed infants (479/617 [77.6%]) exposed to maternal HIV and ART, mean LAZ and WAZ were lower in the EFV/FTC/TDF arm than the DTG arms. Mean LAZ difference (95% CI) between DTG+FTC/TDF and EFV/FTC/TDF arms was 0.4 (0.1, 0.6; p=0.0056) at Week 26 and 0.3 (0.1, 0.6; p=0.01) at Week 50. Mean WAZ difference (95% CI) between DTG+FTC/TDF and EFV/FTC/TDF arms was 0.3 (0.0, 0.5; p=0.035) at Week 26 and 0.3 (0.1, 0.6; p=0.0094) at Week 50. There were no apparent mean differences between DTG+FTC/TAF and DTG+FTC/TDF arms in LAZ or WAZ at Weeks 26 or 50. Mean WHZ were similar between arms. A lower proportion of infants in the DTG+FTC/TAF and DTG+FTC/TDF arms were severely stunted compared to the EFV/FTC/TDF arm (Table): difference (95% CI) -5.7% (-13.3%, 1.9%) for both arms at Week 26, and -7.2% (-15.0%, 0.7%) and -7.0% (-14.9%, 1.0%) at Week 50, respectively.
While infants in the EFV/FTC/TDF arm were smaller than in the DTG arms, growth was similar following exposure to TDF vs. TAF in combination with DTG/FTC. Rates of severe stunting were high across all arms, and present in one in five EFV/FTC/TDF-exposed 1-year old infants. Infant growth should be factored into choice of optimal maternal ART regimen during pregnancy and breastfeeding.