Background:
Several studies in non-pregnant adults have suggested increases in blood pressure (BP) associated with dolutegravir (DTG) use, however findings are mixed. There are notably few data from (i) sub-Saharan Africa and (ii) pregnant and postpartum women living with HIV (PLH).
Methods:
We compared BP in PLH initiating DTG- versus Efavirenz-(EFV-) containing regimens initiated during pregnancy in a secondary analysis of the DolPHIN-2 trial (NCT03249181). At sites in Uganda and South Africa, PLH initiating ART ≥28w gestation were randomly assigned tenofovir+lamivudine/emtricitabine and either DTG or Efavirenz (EFV) as first-line therapy. PLH were followed with 8 study visits through 72 weeks postpartum including standardised anthropometric and BP assessments including sized cuffs. Given physiologic changes in BP during the perinatal period, analyses focused on systolic (sBP) and diastolic BP (dBP) at 24, 48 and 72 weeks postpartum in PLH assigned to DTG vs EFV using mixed effects linear models adjusted for age, BMI, site, and enrolment BP; temporal changes were evaluated using time interactions in separate models. In addition, we examined the risk of incident hypertension (BP>140/>90) among those with BP<140/<90 at enrolment and 6 weeks postpartum.
Results:
Overall 268 women were enrolled (median age 28 years; median gestation 31 weeks; median BMI 28kg/m2). Participants in South Africa had consistently higher BMI, sBP and dBP compared to those in Uganda at enrolment and throughout follow-up. However after accounting for site and baseline values there were no associations observed between DTG use and sBP (beta=2.2mmHg; 95% CI -0.6 to 5.0), dBP (beta=1.54mmHg; 95% CI: -0.9 to 4.0) or weight (beta=0.7kg; 95% CI -0.9 to 2.3) through 72w postpartum. Four participants had hypertension detected at enrolment; during follow-up 8 participants switched treatment assignment, none related to blood pressure or weight gain. There was no association between DTG versus EFV and incident hypertension at any time point.
Conclusions:
These reassuring RCT data suggest that after adjustment for important pre-treatment covariates there was no association between DTG vs EFV initiated late in pregnancy and BP through 18 months postpartum. There is ongoing need for attention to the long-term cardiometabolic effects of DTG use in PLH.