Background:
The increased risk of stroke conferred by HIV may be greater for women than for men. Little is known about potential mechanisms driving the differential stroke risk by sex in people with HIV (PWH). We examined whether sex modifies the effect of traditional and HIV-related risk factors associated with stroke in PWH.
Methods:
We analyzed the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort of PWH receiving HIV care. Strokes occurring in PWH from 5 sites across the U.S. were centrally adjudicated by neurologists. Follow-up in care was from ~2005-2020 (end dates varied by site). The observation period began at the date of stroke surveillance by site or the initial CNICS visit date plus 6 months and ended at the earliest of: stroke, last visit plus 9 months, death, or administrative censoring date. Data from the CNICS central data repository included demographics, laboratory values, medication prescriptions, and diagnoses. Substance use, depression, and physical activity were from the CNICS clinical assessment of patient-reported outcomes collected as part of care visits. Cox survival models were used to assess the hazard ratio of stroke for predictors of interest, female sex, and the interaction between predictors of interest and female sex adjusted for age, race/ethnicity, and site.
Results:
Among 13,584 PWH (mean age 44 years, 19% women, 40% Black, 81% with viral load < 400 copies/mL), there were 147 incident strokes during follow-up (mean follow-up 5.8 years for women, 5.5 years for men). In the overall cohort, age (HR 1.63 per 10 years, 95% CI 1.34-1.98, p< 0.001) but not sex (HR 1.19 for women, 95% CI 0.77-1.82, p=0.43) was a risk factor for stroke. However, a statistically significant age-by-sex interaction was observed (p=0.005). At younger ages, the risk of stroke was higher for women compared with men (HR 2.09 for women versus men at age 40, 95% CI 1.27-3.44, p=0.004), whereas with older age, this difference was no longer present. Conversely, the risk of stroke associated with having a detectable viral load or using methamphetamine was greater for women than for men (Table).
Conclusions:
Stroke risk was higher for some women with HIV compared with men, although this effect declined with older age. The effect of other risk factors on stroke, including viremia, differed between women and men with HIV. Investigation into the mechanisms underlying these differences and how this may translate into sex-specific stroke treatment and prevention is warranted.
Differences in the associations of risk factors with stroke by sex