Sex differences in cardiovascular disease in people with and without HIV

This study aims to assess the association between HIV infection and cardiovascular disease (CVD) incidence, with a focus on sex differences and the role of immune status.

Retrospective cohort study using electronic health records from the All of Us (AoU) Research Program. We identified people with HIV (PWH) and matched them to people without HIV (PWoH) using propensity score matching (PSM) (1 : 5) by sex, age, and race/ethnicity. The matched cohort was then restricted to participants who were free of CVD before the index date.

We used Cox proportional hazards models, including an interaction term between sex and HIV status, to assess sex differences in the association between HIV status and incident CVD, adjusting for potential confounders. Subgroup analyses evaluated effect modification by viral suppression (HIV RNA < 50 copies/ml) and preserved immune function (CD4+ cell count >500 cells/μl).

After PSM, we identified 4803 PWH without preexisting CVD and matched them with 24 276 PWoH. Compared to their matched PWoH, women with HIV had an elevated adjusted hazard ratio (aHR) for CVD [aHR = 1.933, 95% confidence interval (CI): 1.709-2.188] than men with HIV (aHR = 1.435, 95% CI: 1.313-1.568). In subgroup analyses, compared with women without HIV, women with HIV remained at higher risk of CVD despite viral suppression (aHR = 1.929, 95% CI: 1.565-2.378) or preserved immune function (aHR = 1.813, 95% CI: 1.455-2.259). In contrast, no significant differences were observed between men with HIV and well controlled men without HIV (aHR = 1.133, 95% CI: 0.964-1.332).

Understanding sex-specific drivers of CVD risk is crucial for developing targeted interventions to prevent CVD in women with HIV and men with HIV.