Compared with men with HIV, women with HIV who had a stroke were younger, more likely to be non-White, and to have treated hypertension and a higher BMI.

“We have observed sex differences in stroke risk across several large cohorts of people with HIV,” Felicia Chow, MD, explains. “In one clinical care database, people with HIV were at increased risk for ischemic stroke compared with people without HIV, but interestingly, the excess risk was driven by women with HIV in the cohorts.”

However, the researchers “weren’t sure what to make of it,” Dr. Chow adds. “This prompted us to examine whether risk factors for stroke differed altogether between women and men or whether the impact of various cardiovascular and HIV-related factors on stroke risk differed between women and men.”

For a study presented at CROI 2023, Dr. Chow and colleagues examined individuals with HIV receiving care at five sites in the United States. Neurologists centrally adjudicated strokes, and follow-up occurred from 2005-2020.

Impact of Age & Comorbidities on Women’s Stroke Risk

The study included 13,573 people with HIV (mean age, 44; 19% women; 40% Black), most of whom (81%) had a viral load of less than 400 copies/mL. Over a mean follow-up period of about 5.8 years for women and 5.5 years for men, 162 strokes occurred.

“In an adjusted model, we first identified risk factors for stroke in the entire cohort,” Dr. Chow explains. “There were no surprises there—we found that aging by 10 years, having treated hypertension or diabetes, or using a statin, which can be viewed as a proxy for having hyperlipidemia, were all risk factors for stroke. In fact, the effect size of each factor was comparable, with each one being associated with a 50% to 65% higher risk for stroke. Similarly, a detectable viral load was also associated with an approximately 60% higher risk for stroke, whereas—for every 100 more CD4 cells—stroke risk declined by about 30%.”

The researchers then examined the 162 individuals who had an incident stroke during follow-up, which demonstrated “some differences” between women and men, according to Dr. Chow.

“Compared with men, women who had a stroke were younger, more likely to be non-White, and to have treated hypertension and a higher BMI,” she says. “They were also more likely to have a detectable viral load and a higher score on the PHQ-9, which is indicative of more symptoms of depression, compared with men.”

In an adjusted model that included an interaction term, the study team observed that age modified the effect of sex on stroke risk.

“In other words, a woman aged 40 in the cohort had a two-fold higher risk for stroke compared with a man of the same age, whereas by age 60, the increased risk for stroke associated with being a woman was no longer present—in fact, being a woman was protective,” Dr. Chow says. “Further, the negative effect of having a detectable viral load was higher for women. We also saw an interesting signal that having treated hypertension was associated with a greater increased risk for stroke among women compared with men, although we did not observe any sex differences in the relationship between actual blood pressure measurements and stroke risk.”

Educating Women & Informing Future Research

The findings “have to be interpreted in the context of several limitations,” according to Dr. Chow.

“For example, although the racial/ethnic distribution among women and men differed significantly, we were not able to stratify our analyses further to compare women and men within race/ethnicity groups,” she says. “This is relevant because we know there are racial/ethnic disparities in stroke rates in the general population in the US, driven, at least in part, by socio-structural variables that impact health and well-being, including in people living with HIV.”

She also says “a lot of work” needs to be done to understand the increased stroke risk. “I am hopeful that, as we learn more—such as whether higher levels of inflammation in women could explain the greater stroke risk—we will be able to develop more targeted, sex-specific strategies.”

For now, Dr. Chow notes that clinicians should be aware of the increased risk among women with HIV. “Clinicians can help to educate women about stroke and stroke risk factors and empower them to take ownership of lowering stroke risk by targeting modifiable cardiovascular and other risk factors through lifestyle changes starting as early as possible,” she says.