PROJECT SUMMARY/ABSTRACT
Cognitive deficit is prevalent in people living with HIV. Mounting evidence has implicated systemic inflammation
and neuroinflammation in cognitive deficit via HIV-specific mechanisms; however, the cognitive effects of
longitudinal change in inflammation are poorly understood. Preliminary findings from a non-intervention cohort
of adults living with HIV show unexplained cognitive decline across domains over a 2-year period. I
hypothesize that this cognitive decline is associated with an increase in systemic inflammation in
people living with HIV. Thus, to address Aim 1, I will conduct a secondary analysis examining blood plasma
IL-6, CRP, sCD14, and sCD163 as predictors of NIH Toolbox Cognitive Battery change in this cohort. This aim
will provide valuable information on the longitudinal relationship between inflammation and cognition in the
absence of intervention, which may be used as a comparison point for interventional research.
Critically, interventions to reduce systemic inflammation in people living with HIV are in their infancy. Heavy
alcohol use is prevalent among people living with HIV. Alcohol use exacerbates systemic inflammation and
may contribute to increased neuroinflammation, operationalized as disruptions in brain myo-inositol and
choline, in people living with HIV; relatedly, alcohol use is associated with increased cognitive deficit in people
living with HIV. Alcohol reduction is known to partially remediate brain myo-inositol and choline disruptions and
cognitive deficit in seronegative populations. However, the added physiological burden of HIV may reduce the
beneficial impact of alcohol reduction. Having described inflammatory and cognitive change in the absence of
intervention, I will turn to secondary analyses of an interventional study of alcohol reduction to assess its
effectiveness in remediating alcohol-related cognitive deficit in this population. I hypothesize that alcohol
reduction will associate longitudinally with reduced magnetic resonance spectroscopy (MRS) markers
of neuroinflammation and that reduced neuroinflammation will associate longitudinally with improved
cognition in people living with HIV. In Aim 2, I will examine Timeline Follow-Back drinks/month before and
after intervention and HIV serostatus as predictors of brain MRS myo-inositol, choline, and N-acetylaspartate
over 4 time points. In Aim 3, I will assess change in brain MRS myo-inositol, choline, and N-acetylaspartate in
relation to NIH Toolbox Cognitive Battery change over 4 time points. This project, building on the baseline
established by Aim 1, will provide critical insight into the effectiveness of alcohol reduction as an intervention in
this vulnerable population.
