Sex Differences in Cardiovascular Disease and Associated Factors in People Living With HIV: Evidence From All of Us Program

Background People living with HIV (PLWH) face a higher risk of cardiovascular disease (CVD), with significant sex differences in outcomes. However, it is unclear whether these differences are driven by distinct risk factor profiles or by a differential impact of shared risk factors. This study aimed to identify factors associated with CVD among PLWH and to specifically assess for effect modification by sex using a large, diverse nationwide database. Methods We utilized data from the All of Us Research Program (AoU). The primary outcome was a composite of coronary artery disease or stroke. We used multivariable logistic regression to identify factors associated with CVD in the overall cohort. To assess for effect modification, we introduced interaction terms between sex and key covariates. Subsequently, sex-stratified analyses were performed to explore these differences. Results Among 6464 PLWH (4608 men and 1856 women), women had a higher prevalence of CVD than men (24.8% vs. 21.9%, p = 0.011). We identified significant interaction effects between sex and several key risk factors, including hypertension, unemployment and hyperlipidaemia (p < 0.05 for all). In stratified analyses comparing women to men within these risk groups, the association of hypertension with CVD was substantially stronger in women than in men (adjusted odds ratio [aOR] = 4.928, 95% CI: 2.827–8.586). Similarly, the effects of unemployment and hyperlipidaemia on CVD were more pronounced in women. In fully stratified models, a detectable viral load was a significant risk factor for CVD only among men (aOR = 1.524, 95% CI: 1.130–2.049). Conclusions While many traditional and HIV-specific CVD risk factors are shared between men and women living with HIV (WLWH), our findings reveal that the magnitude of their effect is not uniform. The impact of key risk factors, particularly hypertension, is substantially greater in women, suggesting a heightened vulnerability to these exposures. These findings underscore the critical need for sex-specific risk assessments and aggressively tailored prevention strategies for PLWH.