title: The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning.
abstract: Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect one's risk for neurocognitive impairment. Literature on both HIV and stimulant use indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study, the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning were examined longitudinally over a 10-year period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-highly active antiretroviral therapy (HAART) data were examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No four-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple three-way interactions were found that involved genotype and HIV status. All immunologically related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only C-C chemokine ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologically related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however, their impact is minor. Being consistent with findings from another cohort, dopamine (DA)-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV+ individuals.
authors.affiliation: Department of Neurology, National Neurological AIDS Bank, David Geffen School of Medicine, University of California, Los Angeles, CA, USA, ajlevine@mednet.ucla.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Sandra
authors.initials: S
authors.lastname: Reynolds
authors.forename: Christopher
authors.initials: C
authors.lastname: Cox
authors.forename: Eric N
authors.initials: EN
authors.lastname: Miller
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.forename: James T
authors.initials: JT
authors.lastname: Becker
authors.forename: Eileen
authors.initials: E
authors.lastname: Martin
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D018932:Chemokine CCL2 / Q000235:genetics; D054405:Chemokine CCL3 / Q000235:genetics; D003071:Cognition / Q000187:drug effects* / Q000502:physiology*; D015986:Confounding Factors, Epidemiologic; D004298:Dopamine / Q000235:genetics; D005838:Genotype; D006716:Homosexuality / Q000706:statistics & numerical data; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology / Q000235:genetics; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D015995:Prevalence; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000453:epidemiology* / Q000235:genetics*
chemical_list: C111835:CCL2 protein, human; C515429:CCL3 protein, human; D000697:Central Nervous System Stimulants; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D004298:Dopamine
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