In IMPAACT 2010, a trial comparing 3 antiretroviral treatment (ART) regimens initiated in pregnancy, dolutegravir (DTG)–particularly in combination with tenofovir alafenamide (TAF)–was associated with more weight gain but better pregnancy outcomes than ART containing efavirenz (EFV) or tenofovir disoproxil fumarate (TDF). The impact of these weight gain patterns during pregnancy on gestational diabetes is unknown. We evaluated glycated hemoglobin (HbA1c) and glucose in study participants.
643 pregnant women with HIV in 9 countries were randomized 1:1:1 to start open-label DTG+emtricitibine (FTC)/TAF, DTG+FTC/TDF, or EFV/FTC/TDF at 14-28 weeks’ gestation. Following a protocol amendment partway through the trial, we sampled maternal HbA1c and random glucose at study entry, 12 weeks after enrolment (antepartum) and delivery; and neonatal glucose within 48 hours of birth. By-arm differences in mean maternal HbA1c and glucose levels and time-averaged area under the curve (AUC) and infant glucose levels were evaluated using student’s t-tests. We compared the proportion of women with post-baseline HbA1c ?5.7% (prediabetic) between arms using Wald Tests and described the proportion of women with HbA1c ?6.5% (defined as diabetic).
348 mothers and 65 infants had HbA1c and/or glucose result available (114 in the DTG+FTC/TAF; 116 in the DTG+FTC/TDF; and 118 in the EFV/FTC/TDF arms); 78% enrolled in Africa. Maternal enrolment medians were: age 25.9 years, gestational age 21.5 weeks, BMI 24.1 kg/cm2, HIV-1 RNA 3.1 log10, and CD4 466 cells/mm3. No women had a diabetes diagnosis at entry. Maternal mean HbA1c levels (Table) and mean time-averaged HbA1c AUC did not differ significantly between arms. Seven percent of women in the DTG+FTC/TAF arm, 6.0% in the DTG+FTC/TDF arm, and 3.4% in the EFV/FTC/TDF arm had at least one post-baseline HbA1c ?5.7% (p?0.21 for between-arm comparisons). One woman in the DTG+FTC/TAF arm developed HbA1c ?6.5% post-baseline. The DTG+FTC/TDF arm had a higher mean time-averaged AUC glucose vs the EFV/FTC/TDF arm (mean difference [95% CI]: 0.17 [0.00, 0.34] mmol/L). Mean infant glucose levels ?48 hours of birth were similar by arm.
In this randomized trial with modest sample sizes of participants assessed for HbA1c and random glucose, we did not observe significant differences in maternal HbA1C by ART regimen, nor clinically meaningful differences in maternal or infant random glucose.