HIV infection is commonly associated with substance use. Although previous research has shown that drugs of abuse can alter blood brain barrier function, the effect of substance use on central nervous system (CNS) inflammation is unknown in HIV+ individuals. We examined the role of past drug use in neuroinflammation in HIV.
Participants with variable substance use history (defined as none, occasional, or dependent) were recruited into a CNS early HIV infection study. All participants were enrolled when antiretroviral therapy (ART)-naïve, and initiated ART during follow up outside of the study. Cerebrospinal fluid (CSF) 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 CSF and plasma neopterin, a marker of macrophage activation, and neuropsychological testing performance pre-and post-ART between groups with different past drug use.
A total of 80 male participants (no past drug use: n=16, occasional past drug use: n=24, dependent past drug use: n= 40) were enrolled and followed longitudinally. No differences in age, plasma and CSF HIV viral load, or blood and CSF WBC count were observed between groups at baseline. Mixed model analyses revealed that pre-ART, plasma and CSF neopterin were elevated in the dependent past drug use group compared to no past drug use group (plasma: β= +7.2, SE = 3.5, p = 0.041; CSF: β= +6.4, SE = 3.0, p = 0.039). The difference in neopterin levels was attenuated post-ART in plasma (β=+3.5, SE = 2.1, p = .105), but persisted in the CSF (β= +7.2, SE = 3.5, p = 0.04). Although no difference was observed in neuropsychological testing performance pre-ART (β= -0.19, SE =.16, p =0.25), dependent past drug use group had reduced improvement in testing scores post-ART compared to the no past drug use group (β= -0.60, SE =.22, p <0.01).
We observed elevations in plasma and CSF inflammation and sustained abnormal neuropsychological testing performance in HIV+ participants with a history of dependent drug use as compared to no drug use. Differences in the CNS persisted after ART. Drug use history should be actively considered in interpretation of HIV-related CNS research.
L. H. Chen,
K. Robertson, None
D. Fuchs, None
R. Price, None
S. Spudich, None