Date of Award

1-1-2018

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Serena Spudich

Abstract

Neuroinflammation has been implicated as a major contributor to neuronal injury in HIV-associated neurocognitive disorders (HAND). Previous in vitro and animal studies have shown that drugs of abuse can create a pro-inflammatory environment in the CNS that can potentiate HAND; however, clinical research studies are lacking, especially during the early years of HIV infection when therapeutic intervention would likely make the greatest difference in disease progression. A total of 82 male participants with variable drug use history (no drug use: n=17, occasional drug use: n=25, heavy drug use: n= 40) were enrolled within one year of HIV infection and followed longitudinally. All participants were enrolled when antiretroviral therapy (ART)-naïve, and initiated ART during follow up outside of the study. Paired plasma and cerebrospinal fluid (CSF) samples and neuropsychological testing data were collected from participants at baseline, 6 weeks, and every 6 months thereafter for up to four years. Mixed model analyses were conducted to compare the effect of drug use on levels of CSF and plasma neopterin, a marker of macrophage activation, and neuropsychological testing performance. Pre-ART, both plasma and CSF neopterin levels were elevated in the heavy drug use group compared to the no drug use group (plasma: β = +7.1, SE = 2.4, p = 0.003; CSF: β = +7.4, SE = 1.9, p

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