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

Alyssa C. Vecchio, Dionna W. Williams, Yanxun Xu, Danyang Yu, Deanna Saylor, Sarah Lofgren, Riley O'Toole, David R. Boulware, Noeline Nakasujja, Gertrude Nakigozi, Alice Kisakye, James Batte, Richard Mayanja, Aggrey Anok, Steven J. Reynolds, Thomas C. Quinn, Ronald H. Gray, Maria J. Wawer, Ned Sacktor, Leah H. Rubin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalBrain, Behavior, and Immunity
StatePublished - Mar 1 2021

Bibliographical note

Funding Information:
This study was sponsored by the NIH (MH120693, MH099733, MH075673, MH080661-08, L30NS088658, NS065729-05S2) with additional funding from the Johns Hopkins Center for Global Health. This study was also supported in part by the Division of Intramural Research, NIAID, NIH. We would also like to thank the participants and staff of the Rakai Health Sciences Program for their time and effort in the successful conduction of this study.

Publisher Copyright:
© 2020 Elsevier Inc.


  • Cognition
  • Global health
  • HIV
  • Inflammation
  • Sex


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