Differences in Cognitive Function Between Women and Men With HIV

Pauline M. Maki, PhD; Leah H. Rubin, PhD; Gayle Springer, MLA; Eric C. Seaberg, PhD; Ned Sacktor, MD; Eric N. Miller, PhD; Victor Valcour, MD, PhD; Mary A. Young, MD; James T. Becker, PhD; Eileen M. Martin, PhD


J Acquir Immune Defic Syndr. 2018;79(1):101-107. 

In This Article

Abstract and Introduction


Background: Women may be more vulnerable to HIV-related cognitive dysfunction compared with men because of sociodemographic, lifestyle, mental health, and biological factors. However, studies to date have yielded inconsistent findings on the existence, magnitude, and pattern of sex differences. We examined these issues using longitudinal data from 2 large, prospective, multisite, observational studies of US women and men with and without HIV.

Setting: The Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS).

Methods: HIV-infected (HIV+) and uninfected (HIV−) participants in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study completed tests of psychomotor speed, executive function, and fine motor skills. Groups were matched on HIV status, sex, age, education, and black race. Generalized linear mixed models were used to examine group differences on continuous and categorical demographically corrected T-scores. Results were adjusted for other confounding factors.

Results: The sample (n = 1420) included 710 women (429 HIV+) and 710 men (429 HIV+) (67% non-Hispanic black; 53% high school or less). For continuous T-scores, sex by HIV serostatus interactions were observed on the Trail Making Test parts A & B, Grooved Pegboard, and Symbol Digit Modalities Test. For these tests, HIV+ women scored lower than HIV+ men, with no sex differences in HIV− individuals. In analyses of categorical scores, particularly the Trail Making Test part A and Grooved Pegboard nondominant, HIV+ women also had a higher odds of impairment compared with HIV+ men. Sex differences were constant over time.

Conclusions: Although sex differences are generally understudied, HIV+ women vs men show cognitive disadvantages. Elucidating the mechanisms underlying these differences is critical for tailoring cognitive interventions.


Approximately 50% of HIV-infected (HIV+) individuals develop cognitive impairment.[1,2] Cognitive function in HIV+ men has been well characterized because most HIV+ individuals living in the United States and participating in cohort studies are men.[1–3] Women comprise approximately 25% of HIV cases[4] in the United States and half of global cases.[5] HIV+ women in the Women's Interagency HIV Study (WIHS)[6] show small but significant deficits in cognitive function, particularly in verbal learning and memory, and processing speed.[6,7] Few studies have directly compared cognitive function of HIV+ women and men, even though cognitive profiles of HIV+ women cannot be assumed to be the same as HIV+ men.[8] Including HIV-uninfected (HIV−) controls in such comparisons is important to determine the expected pattern of sex differences.

Women may be more vulnerable to HIV-associated cognitive impairment compared with men because of biological differences (eg, hormonal and pharmacokinetic) as well as poverty, low literacy, low education, substance abuse, poor mental health, early life stressors, trauma, and barriers to health care. Some studies suggest greater cognitive vulnerabilities in HIV+ women compared with HIV+ men,[3,9,10] whereas others suggest no difference[11] or show differences only in the pattern of impairment.[12]

We compared cognitive test performance in a matched subset of HIV+ and HIV− women from the WIHS and HIV+ and HIV− men from the Multicenter AIDS Cohort Study (MACS) who were comparable in age, education, and black race. Given previous findings,[13–15] we predicted that HIV+ women would perform worse than HIV+ men.