Evaluating the association of antiretroviral therapy and immune status with hypertensive disorders of pregnancy among people with HIV

Abstract

The aim of this study was to examine the association of timing of antiretroviral therapy (ART) initiation and ART class with risk of new-onset hypertensive disorders of pregnancy (HDP) among people with HIV (PWH).Design: An observational study of participants in the multisite Surveillance Monitoring for ART Toxicities (SMARTT) study.Methods: Data were abstracted from medical records of pregnant PWH enrolled in SMARTT (January 30, 2015 to March 25, 2019. New-onset HDP included gestational hypertension, preeclampsia/eclampsia, or HELLP syndrome. We examined the associations of clinical risk factors and three exposures of interest, each in a separate model, with risk of new-onset HDP. Log-binomial regression models were fit using generalized estimating equations to account for correlations within people. Exposures included timing of ART initiation, antiretroviral class among those on therapy at conception, and antiretroviral class among those initiating treatment during pregnancy.Results: Of 1038 pregnancies in this cohort, 973 were singletons with complete data on HDP, with ART use in 948. Overall, 9% had a new-onset HDP, 10% had chronic hypertension, and 81% had no hypertension. Diabetes [adjusted relative risk (aRR) 2.44, 95% confidence interval (95% CI) 1.42-4.21] and first/second trimester CD4 þ cell count less than 200 cells/ml (aRR 1.99, 95% CI 1.21-3.27) were associated with a greater risk of new-onset HDP. Risk of new-onset HDP was similar by antiretroviral class, but those initiating ART after 20 weeks' gestation had a greater risk (aRR 1.93, 95% CI 1.12-3.30) compared with those receiving ART at conception. Conclusion:In this large, diverse cohort of pregnant PWH, worse early pregnancy immune status and later ART initiation were associated with an increased risk of HDP while ART class was not.

Is there a link between antiretroviral therapy and hypertensive disorders of pregnancy?

“…In this well designed study [1] from the large SMARTT US-based cohort of pregnant people with HIV (PWH), nearly 20% had hypertensive disorders of pregnancy (HDP), of which about one half was chronic hypertension, and the other half was new-onset HDP. The incidence of new-onset HDP was twice higher in PWH who initiated ART on or after 20 weeks of gestation compared to those taking ART before conception.…”

“…When considering a potential link between ART and HDP, the wide range of conditions with high blood pressure is a limitation, since different pathophysiological mechanisms may be involved. Yee et al [1] hypothesized that ART-induced immune activation exacerbates endothelial dysfunction. If the timing of ART initiation influences the risk of HDP, this may offer a clue to the mechanisms, suggesting that HDP resulting from ART initiation during pregnancy could be due to immune activation, whereas HDP resulting from ART started before the pregnancy could be related to more long-term effects of the medications.…”

“…Saums et al [21] reported that while the overall the risk of HDP was similar among PWH on ART and women without HIV, there were more HDP with integrase strand transfer inhibitor-based versus protease inhibitor-based regimens. The study by Yee et al [1] is among the first to include a large population of PWH taking integrase strand transfer inhibitor (INSTI)-based regimens. INSTI-based regimens were associated with a higher risk of new-onset HDP than NNRTI-based or PI-based regimens, but the difference did not reach statistical significance.…”