Title The longitudinal and interactive effects of HIV status , stimulant use , and host genotype upon neurocognitive functioning Permalink

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 ofHIV status, stimulant use, and genotype upon neurocognitive functioningwere 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, A. J. Levine Department of Neurology, National Neurological AIDS Bank, David Geffen School of Medicine, University of California, Los Angeles, CA, USA S. Reynolds : C. Cox Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA E. N. Miller Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA J. S. Sinsheimer Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA J. S. Sinsheimer Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA J. S. Sinsheimer Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA J. T. Becker Departments of Psychiatry and Neurology and Psychology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA E. Martin Department of Psychiatry, Rush UniversityMedical Center, Chicago, IL, USA N. Sacktor Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA A. J. Levine (*) 11645 Wilshire Blvd., Ste 770, Los Angeles, CA 90025, USA e-mail: ajlevine@mednet.ucla. edu J. Neurovirol. (2014) 20:243–257 DOI 10.1007/s13365-014-0241-y