HIV infection and preeclampsia: reconciling divergent findings across ART eras and study designs

Objective: To contextualize conflicting evidence regarding the association between maternal HIV infection and preeclampsia STUDY DESIGN: We compared Rittenhouse et al. prospective data (2015-2022), where standardized phenotyping and marginal standardization estimated reduced preeclampsia risk in HIV-positive women, with our retrospective population-based analysis (1989-2015), which found increased risk, particularly in HAART-exposed pregnancies. Differences in surveillance, outcome definitions, covariate adjustment, and ART era/regimen were examined, alongside mechanistic hypotheses and suggested additional analyses. Results: In Zambia, HIV infection was associated with lower preeclampsia risk (adjusted RR 0.42, 95% CI 0.26-0.59), persisting across ART strata, viral load, CD4 count, and severe disease. In Naples, HIV-infected women had higher risk versus HIV-negative women (10.2% vs 4.1%; adjusted OR 2.68, 95% CI 1.96 to 3.64), with excess risk concentrated among HAART users. A unifying mechanistic framework posits that long-standing immune suppression or quiescence may lower risk, whereas rapid immune reconstitution after ART initiation may elevate risk. Conclusion: Apparent contradictions between cohorts may reflect context-specific interactions between HIV, ART, maternal immunity, and clinical practice. HIV-positive pregnancies require vigilant monitoring and preconception optimization of ART and cardiometabolic health.