Combination Antiretroviral Therapy and Hypertensive Disorders of Pregnancy

Abstract

OBJECTIVE: To compare the incidence of hypertensive disorders of pregnancy among women living with human immunodeficiency virus (HIV) on combination antiretroviral therapy (ART) to women without HIV, and to evaluate the association of hypertensive disorders of pregnancy with ART regimens or timing of ART initiation. METHODS: We conducted a retrospective cohort study among two overlapping pregnancy cohorts using preexisting databases at a single tertiary care hospital: all pregnant women who delivered during years 2016–2018 (cohort 1) and all women living with HIV who delivered during years 2011–2018 (cohort 2). The primary outcome for both cohorts was any hypertensive disorder of pregnancy; gestational hypertension and preeclampsia were also examined separately. The primary exposure variables were HIV status for cohort 1 and ART regimen (integrase strand transfer inhibitor–containing, protease inhibitor–containing, or non-nucleoside reverse transcriptase inhibitor–containing) for cohort 2. For estimation of risk ratios (RRs), we used a modified Poisson regression with robust error variances. Multivariate models among the women living with HIV in cohort 2 were tested for a statistical interaction between ART regimen and timing of initiation. RESULTS: In cohort 1, among 80 women living with HIV compared with 3,464 women without HIV, there was no difference in the risk of hypertensive disorders of pregnancy (29% in women living with HIV vs 30% in women without HIV, adjusted RR 0.9, 95% CI 0.6–1.3). In cohort 2, among 265 women living with HIV, integrase strand transfer inhibitor–containing regimens were associated with an increased risk for any hypertensive disorder of pregnancy (25% among integrase strand transfer inhibitor vs 10% among protease inhibitor, adjusted RR 2.8, 95% CI 1.5–5.1) and gestational hypertension (20% among integrase strand transfer inhibitor vs 8% among protease inhibitor, adjusted RR 2.8, 95% CI 1.3–5.9) compared with protease inhibitor–containing regimens. Timing of ART initiation was not associated with hypertensive disorders of pregnancy, nor did it significantly alter the associations between ART regimen and hypertensive disorders of pregnancy outcomes. CONCLUSION: Overall the risk of hypertensive disorders of pregnancy was similar among women living with HIV on ART and women without HIV. With greater integrase strand transfer inhibitor use, the greater frequency of hypertensive disorders of pregnancy with these regimens compared with protease inhibitor–containing regimens warrants future evaluation using cohorts with greater sample size.

Blood pressure trajectories during pregnancy and associations with adverse birth outcomes among HIV-infected and HIV-uninfected women in South Africa: a group-based trajectory modelling approach

“…Though limited, data on specific ART drug classes has shown exposure to PIs to be strongly associated with hypertension [ 6 , 33 ]; in our setting nucleoside reverse transcriptase inhibitors regimens are predominantly used rather than PIs which could explain lack of difference by HIV status. Our findings by HIV status are similar to a retrospective cohort study of two overlapping pregnancy cohorts [ 34 ], but differed according to ART status. We found that women classified as hypertensive or as having abnormal trajectories were more likely to have initiated ART in pregnancy; and this could possibly be linked to immune reconstitution, a hyper-inflammatory state associated with ART initiation [ 35 , 36 ], vascular dysfunction and alterations in sympathetic nervous outflow [ 37 ].…”

Maternal endothelial dysfunction in HIV-associated preeclampsia comorbid with COVID-19: a review

“…This increase is believed to be due to immune restoration [ 92 ]. Recent studies show no difference in the risk of PE development between treated and untreated HIV-infected pregnant women [ 93 ], but others have reported findings that do not support the notion that HIV infection has protective qualities against HDP development [ 94 ].…”

“…In contrast, a study of HIV-associated PE women revealed that HIV/HAART is linked to significant downregulation of IL-2, TNF-α and IL-6, with significant decreases in IL-2 and TNF-α observed in preeclamptic women [ 108 ]. Saums et al found that integrase strand transfer inhibitor-containing ARTs had a greater frequency of HDP development than protease inhibitor-containing regimens [ 93 ]. Another study concluded that HIV infection, rather than its pharmacological treatment, induces alterations in markers of endothelial function [ 109 ].…”

A Multi-Objective Approach for Drug Repurposing in Preeclampsia

“…It is interesting that abacavir, an antiviral drug, appears in the list of unique drugs. In general, the administration of antiviral drugs had been associated with an increased risk of preeclampsia [ 53 , 54 ] but it is unclear what is the mechanism involved in this association. Regarding the antiparasitic drugs involved, we found ivermectin, lumefantrine (these two found in the common 36 drugs), disulfiram and bithionol.…”