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ObjectiveWomen may be disproportionately impacted by the negative effect of HIV on cerebrovascular risk. We examined the association of HIV, sex, menopause, and immune activation with cerebrovascular function among women with HIV (WWH) and at risk for HIV from the Women's Interagency HIV Study and men with HIV.DesignCross-sectional.MethodsParticipants were aged at least 40 years with coronary heart disease or at least one cardiometabolic risk factor. All persons with HIV were on antiretroviral therapy with undetectable viral load. Cerebral vasoreactivity was assessed by the transcranial Doppler breath-holding test, with lower vasoreactivity corresponding to worse cerebrovascular function. Menopausal status was determined by anti-Müllerian hormone level. We used mixed effects linear regression to identify factors associated with cerebral vasoreactivity.ResultsMean cerebral vasoreactivity was similar in WWH (n = 33) and women at risk for HIV (n = 16). A trend toward higher cerebral vasoreactivity in WWH compared with men with HIV (n = 37) was no longer present after excluding women on estrogen replacement therapy (n = 3). In women, menopausal status was not significantly associated with cerebral vasoreactivity. WWH with higher cardiovascular risk (-0.14 for each additional cardiometabolic risk factor, P = 0.038), sCD163 (-0.20 per doubling, P = 0.033), and proportion of CD4+CX3CR1+ T cells (-0.14 per doubling, P = 0.028) had lower cerebral vasoreactivity.ConclusionAmong older women at high cardiovascular risk, women with virologically suppressed HIV and women at risk for HIV had similar cerebrovascular function. Our findings, which must be interpreted in the context of the small sample, highlight the contribution of traditional cardiometabolic risk factors and immune activation to cerebrovascular risk in WWH.

ObjectiveTo determine if the greater risk of ischemic stroke observed in women living with HIV infection (WLWH) compared with HIV-uninfected women persists after accounting for both traditional and sex-specific stroke risk factors.MethodsWe performed an observational cohort study of WLWH (n = 1214) and demographics-matched HIV-uninfected women (n = 12 041) seen between 1996 and 2011 at two tertiary care hospitals in Boston. We used Cox proportional hazards regression analyses to model time to ischemic stroke, adjusting first for demographics and traditional stroke risk factors and then for sex-specific stroke risk factors, including menopause and estrogen use. We also constructed demographics-adjusted Cox models to identify HIV-related risk factors associated with ischemic stroke among WLWH.ResultsThe incidence of ischemic stroke was higher among WLWH compared with HIV-uninfected women [incidence rate ratio 2.39, 95% confidence interval (CI) 1.62-3.43]. After adjusting for demographics and traditional stroke risk factors, HIV infection was associated with almost twice the risk of ischemic stroke (hazard ratio 1.93, 95% CI 1.31-2.85). The association of HIV with ischemic stroke persisted after inclusion of sex-specific stroke risk factors in the model (hazard ratio 1.89, 95% CI 1.28-2.81). Among WLWH, longer duration of antiretroviral therapy was associated with lower ischemic stroke risk (hazard ratio 0.86 per year, 95% CI 0.76-0.96).ConclusionThe increased risk of ischemic stroke among WLWH compared with HIV-uninfected women persisted after adjusting for both traditional and sex-specific stroke risk factors. Further investigation into the mechanisms of elevated stroke risk among WLWH, including immunologic factors, will be key for developing targeted preventive strategies for this at-risk population.