Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda

• Published in: Brain, behavior, and immunity Vol. 93; pp. 111 - 118
• Main Authors: Vecchio, Alyssa C., Williams, Dionna W., Xu, Yanxun, Yu, Danyang, Saylor, Deanna, Lofgren, Sarah, O'Toole, Riley, Boulware, David R., Nakasujja, Noeline, Nakigozi, Gertrude, Kisakye, Alice, Batte, James, Mayanja, Richard, Anok, Aggrey, Reynolds, Steven J., Quinn, Thomas C., Gray, Ronald H., Wawer, Maria J., Sacktor, Ned, Rubin, Leah H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-03-2021
• Subjects: Adult; Biomarkers; Cognition; Cohort Studies; Female; Global health; HIV; HIV Infections - complications; HIV Infections - drug therapy; Humans; Inflammation; Male; Neuropsychological Tests; Sex; Uganda; Uganda; Global health; Cognition; Inflammation; HIV; Sex
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2020.12.021

•In the cohort of people living with HIV on antiretroviral therapy (ART), there were no sex differences in cerebrospinal fluid (CSF) inflammatory marker levels.•There were sex differences in cognitive test performance (e.g. men with HIV performed worse on tests of motor, executive function, and fluency compared to women with HIV).•Men with HIV displayed more associations between inflammatory markers and cognitive performance than women with HIV.•Among men with HIV, inflammatory markers (e.g. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70) were associated with 56% of the cognitive domains (e.g. attention, processing speed).•Among women with HIV, inflammatory markers were associated with 33% of the domains (i.e. motor, fluency, and learning).
People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.