Maternal Human Immunodeficiency Virus and Preeclampsia Among a Combined Cohort of Zambian Women

Abstract

Objective: To evaluate the association between maternal HIV infection and preeclampsia. We hypothesized that maternal HIV infection would be associated with a lower risk of preeclampsia, potentially due to HIV-related immunomodulatory effects.

Methods: We combined participants from one observational cohort and two randomized trials conducted at the same facilities in Lusaka, Zambia between 2015 and 2022. The exposure of interest was maternal HIV infection, and the primary outcome was preeclampsia, defined as 1) new-onset (at or after 20 weeks of gestation) hypertension (systolic blood pressure [BP] 140 mm Hg or higher or diastolic BP 90 mm Hg or higher) with concurrent proteinuria (1+ or higher), 2) new onset proteinuria (1+ or higher) in participants with chronic hypertension in the absence of urinary tract infection, or 3) diagnosis of severe preeclampsia. We defined severe preeclampsia as 1) new-onset severe-range BP (systolic 160 mm Hg or higher or diastolic 110 mm Hg or higher), 2) eclamptic seizure, or 3) clinician-initiated preterm delivery (before 37 weeks of gestation) for preeclampsia. Using marginal standardization (parametric g-formula), we estimated the risk of preeclampsia associated with HIV infection. Antiretroviral therapy (ART) exposure and HIV disease severity (viral load, CD4 counts) were assessed as effect modifiers.

Results: Of 4,078 women included in the combined cohort, 186 (4.6%) were diagnosed with preeclampsia, including 43 (2.7%) of 1,590 women with HIV infection and 143 (5.8%) of 2,488 women without HIV infection. Of those with HIV infection, 73.2% were on prepregnancy ART, and 56.7% had an undetectable viral load at study enrollment (median 15 weeks). In analyses standardizing for maternal age, nulliparity, and calendar time of enrollment, HIV infection was associated with lower preeclampsia risk (relative risk 0.42; 95% CI, 0.26-0.59; risk difference -3.5%; 95% CI, -4.9 to -2.1). This reduced risk persisted when stratifying by prepregnancy ART exposure, detectable viral load, and CD4 count at enrollment; findings were similar when applying the more stringent definition of severe preeclampsia.

Conclusion: In this well-phenotyped cohort, women with HIV infection were less likely to have preeclampsia compared with those without HIV infection.