There are growing concerns about weight gain with dolutegravir (DTG) use, with some suggestion of heterogeneity of effects across populations especially among women. However there are no data from pregnancy and the postpartum (PP) period.
DolPHIN-2 (NCT03249181) is an open label trial randomising (1:1) pregnant women from Uganda and South Africa (SA) initiating ART from 28w gestation to DTG vs efavirenz (EFV) plus 2 NRTIs. Maternal weights were measured using standardized procedures at enrolment, <14 days of delivery and at 6, 12, 24 and 48 weeks PP. For this secondary analysis we examined changes in PP weight and body mass index (BMI) between study arms.
Enrolment took place between Jan and Aug 2018, and follow-up data were censored Sept 2019; 230 women (mean age, 28y) were included with median follow-up of 60 months. At enrolment (median gestation, 31w) the mean weight and BMI was 74 kg and 28 kg/m2, respectively, with no differences between trial arms but higher third trimester weight in SA (mean, 81 kg) versus Ugandan (mean, 68 kg) sites. 73%, 61% and 3% of women reported breastfeeding the infant at 12, 24 and 48w PP, respectively, with no differences by arm. Across both arms and sites, mean change in weight from enrolment to 6w PP was -5.9 kg, with mean weight approximately constant from 6 to 48w PP. However this masked notable inter-site differences. In Uganda, there was a small non-significant decrease in mean weight from 6 to 48w PP that was more marked in the EFV arm (DTG: 63.6 to 63.2 kg; EFV: 60.6 to 59.8 kg; p=0.28). In SA, there was a notable but non-significant increase in mean weight over the same period that was more marked in the DTG arm (DTG: 76.1 to 78.3 kg; EFV: 73.0 to 73.7 kg; p=0.33). After adjusting for site and enrolment weight, the overall mean difference in weight change, 48w-6w PP for DTG-EFV, was 1.00 kg (95% CI -0.98 to 2.97; p=0.32). This difference was larger in SA (1.30 kg; 95% CI -2.21 to 4.80) than in Uganda (0.75 kg; 95% CI -1.48 to 2.97; p for interaction=0.82). Similar findings were observed for BMI throughout.
These randomised data show no differences in PP weight changes between DTG and EFV in women initiating ART late in pregnancy. Substantial PP weight gain among SA women points to potential heterogeneity across populations that requires further investigation.