High Levels of Elevated Blood Pressure Among Pregnant and Postpartum Women With HIV, Regardless of Dolutegravir Initiation

Women living with human immunodeficiency virus (HIV, WLWH) are at elevated risk of cardiovascular disease (CVD), compared to both men with HIV and demographically similar women without HIV [1–5]. Hypertension (HTN) is the leading cause of CVD among women globally [6], and the development of a hypertensive disorder in pregnancy (HDP) is associated with a doubling of future CVD risk [7]. Integrase strand transfer inhibitors (INSTIs), primarily dolutegravir (DTG), have been linked to weight gain and a subsequent increase in HTN risk in non-pregnant populations living with HIV [8] and with elevated blood pressure (BP) in pregnant WLWH [9], but data from randomized trials during pregnancy are limited.

In this issue of CID, Hoffman et al report on findings from the IMPACCT 2010/VESTED trial on the effect of initiating dolutegravir (DTG), with tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), versus efavirenz (EFV) in pregnancy on the risk of incident HTN, defined using the 2025 American College of Cardiology/American Heart Association guidelines [10]. Overall, findings were reassuring that there were no differences by study arm in composite incident HTN in the antepartum, postpartum, or overall study periods or in gestational HTN. The authors note that the HTN incidence was numerically higher in the DTG arms. Compared to women initiating EFV, women in the DTG arms weighted slightly more at baseline and gained weight at a slightly faster rate in pregnancy [11], which likely contributes to HTN risk.

Women in the VESTED trial were enrolled in pregnancy and followed through 50 weeks postpartum. Overall, 49% of women experienced incident HTN, the majority of which was due to elevated blood pressure (BP). Among 308 incidence HTN cases, 233 (76%) were due to elevated BP (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg), considered Stage 1 HTN in the updated ACC/AHA guidelines [10]. Although this high level of elevated BP is notable given the young population (median age 26.6 years at enrollment), the clinical importance of incident elevated BP during pregnancy requires clarification. Blood pressure levels naturally rise toward the end of pregnancy due to increased blood volume and the threshold for elevated BP falls below the definition of gestational HTN (defined as systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg at ≥20 weeks gestation) [12]. Still, two thirds of women with elevated BP in pregnancy remained elevated postpartum, suggesting this may be an important group for postpartum intervention to reduce BP. The authors did not examine whether elevated BP in pregnancy was associated with postpartum HTN risk. This remains an important area for future research to define the clinical implications of elevated BP in pregnancy for WLWH.

Despite the high levels of in elevated BP in the VESTED trial, gestational HTN incidence was low (4.3%), with no differences by arm. Hypertensive disorders of pregnancy include gestational HTN, pre-eclampsia, and eclampsia [12]. Only 6 (1%) women in the VESTED trial experienced pre-eclampsia or eclampsia, lower than the ~3% reported in other cohorts of WLWH [13], suggesting these numbers are likely underreported. Preeclampsia is associated with significant morbidity and mortality, as well as a 2-fold increase in the lifetime risk of CVD [14]. Given the rarity of pre-eclampsia at a population level, future work combining and meta-analyzed data across studies may be needed to clarify the effect of DTG on preeclampsia risk for WLWH.

Across study arms, Hoffman et al observed an association between a 5 kg increase in absolute weight and incident HTN during pregnancy. Although absolute weight is an important predictor of HTN risk outside of pregnancy, all pregnant women are recommended to gain at least 5 kg in pregnancy [15], making the interpretation of these findings in pregnancy unclear. Fortunately, the authors also examined the effect of gestational weight gain (GWG), a better indicator of weight gain in pregnancy, on HTN incidence. As has been observed in other studies, GWG above recommended levels [15] was associated with incident HTN in the antepartum period. The effect of GWG on incident gestational HTN or on postpartum HTN was not evaluated. Given the high levels of sustained elevated BP postpartum observed in the VESTED trial, it is critical to understand if high GWG is associated with postpartum HTN risk.

During pregnancy, both GWG and pre-pregnancy body mass index (BMI) are important indicators of perinatal and cardiometabolic risk. The Institute of Medicine (IOM) defines optimal levels of absolute and rate of GWG based on a women’s pre-pregnancy BMI [15]. It is not clear if the authors took into account a women’s pre-pregnancy BMI when defining GWG above or below IOM recommendations. Only 54% of the VESTED trial population was normal BMI at enrollment [11], emphasizing the importance of accounting for pre-pregnancy BMI category when estimating the effect of GWG on HTN incidence.

Suboptimal GWG affects HTN risk in pregnancy and the risk of the risk of adverse pregnancy outcomes. Women who gain too little weight in pregnancy are at an increased risk of preterm birth and small for gestational age (SGA) [16], while those who gain too much are at an increased risk of high birthweight, large for gestational age, and future cardiometabolic risk [17–20]. The VESTED trial previously reported that GWG <0.18 kg/week was associated with an increased risk of a composite adverse birth outcome and small for gestational age [11], whereas GWG ≥ 0.59 kg/week increased the risk of HTN in the antepartum period. Many WLWH live in resource limited settings where both obesity and food insecurity coexist, indicating that additional work may be needed to define optimal GWG based on pre-pregnancy weight for WLWH. Interventions to support healthy GWG for WLWH may help to improve pregnancy and cardiometabolic outcomes but need to include strategies to address too little and too much GWG.

Overall, the findings from Hoffman et al provide reassuring data that DTG initiated in pregnancy does not increase the risk of gestational HTN or HTN in pregnancy or postpartum. Nevertheless, the findings also highlight a high burden of elevated BP among young women healthy enough to get pregnant. The US and European HIV guidelines were recently updated to recommend statins for people with HIV with low to moderate CVD risk based on the landmark REPRIEVE trial [21], but these recommendations only extend to people >40 years of age and excluded pregnant women. Findings from the VESTED trial highlight that young WLWH are an important population for CVD prevention, with pregnancy offering an important opportunity for intervention. Additional work is urgently needed to understand the drivers and clinical implications of HTN in young WLWH of reproductive age in order improve CVD outcomes for WLWH.