Neurocognitive Complications of HIV Infection in Women: Insights from the WIHS Cohort

Although sex differences in brain function and brain disorders are well documented, very few studies have had adequate number of women to address sex-related factors contributing to HIV-associated brain dysfunction. Compared to men living with HIV (MLWH), women living with HIV (WLWH) may be at greater risk for cognitive dysfunction and decline due to biological factors (e.g., hormonal, immunologic) and issues common in underserved communities including poverty, low literacy levels, mental health and substance abuse, barriers to health-care services, and environmental exposures. To address this issue, we review relevant cross-sectional and longitudinal findings from the Women's Interagency HIV Study (WIHS), the largest study of the natural and treated history of WLWH, as well as other studies focusing on cognitive complications of HIV in women. We provide evidence that WLWH are more cognitively vulnerable than MLWH and that there are differences in the pattern of cognitive impairment. We next discuss factors that contribute to these differences, including biological factors (e.g., inflammation, hormonal, genetic) as well as common comorbidities (mental health, substance use, vascular and metabolic risk factors, coinfections and liver function, non-antiretroviral medications, and genetic markers). These findings demonstrate the importance of considering sex as a biological factor in studies of cognitive dysfunction and suggest avenues for future research.