Abstract
Despite advancements in antiretroviral therapy, mild cognitive deficits persist in nearly half of people with HIV (PWH). The profile of impairment in HIV is highly variable with deficits observed in a range of cognitive domains. Despite evidence of greater cognitive impairment among women with HIV (WWH) vs. men with HIV (MWH), it is unclear how MWH and WWH differ in the type of cognitive impairment and in risk factors associated with cognitive impairment profiles. In a large and well-characterized sample of PWH, we used machine learning to identify profiles of cognitive functioning and their associated factors overall and within sex. Participants included 1,666 PWH (201 WWH; 1,465 MMH) from the HIV Neurobehavioral Research Program who completed a neuropsychological test battery at their baseline visits. Using demographically-adjusted T-scores from 13 test outcomes assessing motor skills, executive functioning, attention/working memory, episodic learning and memory, verbal fluency, and processing speed, we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores (MCLUST R package). Random forest models were used to determine how sociodemographic (e.g., age, education), clinical (e.g., depressive symptoms, substance use disorder), and biological (e.g., HIV disease characteristics) factors differentially related to membership within a cognitive profile. All analyses were repeated within sex. Three cognitive profiles were identified overall and within each sex. Overall and within MWH, there were unimpaired and global weakness profiles. The third profile in the total sample demonstrated relatively weak auditory attention whereas in MWH showed relative strengths in attention and processing speed. Conversely, there was no unimpaired profile among WWH. Rather, WWH demonstrated separate profiles reflecting weakness in motor skills, a relative weakness in learning and delayed recall, and global weaknesses with spared recognition memory. Despite different cognitive profiles by sex, the most discriminative factors were similar between men and women and included reading level (cognitive reserve), current and nadir CD4 count, plasma HIV viral load, duration of HIV disease, age, depressive symptoms, and race/ethnicity. Findings fill a knowledge gap concerning sex differences in cognitive impairment in PWH and inform personalized risk reduction and therapeutic strategies.
Highlights
The Human Immunodeficiency Virus (HIV) enters the central nervous system (CNS) within days of initial infection [1], in many cases leading to neurological, cognitive, and behavioral complications
Our results do not negate the heterogeneity in cognitive function in HIV-uninfected individuals but rather highlights the heterogeneity among people with HIV (PWH) that can often be masked by a dichotomous HIV-associated neurocognitive disorders (HAND) categorization
Given the relative sample sizes, the cognitive patterns in the total sample were in greater alignment with those found among men with HIV (MWH) compared to women with HIV (WWH)
Summary
The Human Immunodeficiency Virus (HIV) enters the central nervous system (CNS) within days of initial infection [1], in many cases leading to neurological, cognitive, and behavioral complications. These psychosocial risk factors may have biological effects on the brain that lead to reduced cognitive reserve among WWH [23, 24] as evidenced by findings of greater susceptibility of cognitive function to the effects of mental health factors (e.g., depression) among WWH vs MWH [25] Biological factors such as sex steroid hormones (e.g., estrogen, testosterone) and female-specific hormonal milieus (e.g., pregnancy, menstrual cycle, menopause transition) may contribute to sex differences in cognitive test performance in PWH. We determined how sociodemographic (e.g., age, education, race/ethnicity), clinical (e.g., functional status, depression, substance use disorders) and biological (e.g., measures of HIV disease severity, ART use, cardiovascular comorbid conditions, Hepatitis C co-infection) factors related to cognitive profiles within women and men. We expected that similar sociodemographic/clinical/biological determinants would distinguish cognitive profiles (e.g., age, education, race, HIV viral load) among WWH and MWH; in line with previous research [25], we expected that depressive symptoms would be more strongly associated with cognitive impairment profiles among WWH than MWH
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