Neuropsychological performance of HIV-infected individuals and its association with Antiretroviral Resistance, Methamphetamine Use, Hepatitis C Virus, and CSF HIV RNA levels

• Published in: Journal of neurovirology 2007-01, Vol.13, p.84-84
• Main Authors: Hightower, G K, Letendre, S L, Cherner, M, Cachay, E R, Gibson, S, Ellis, R, Ignacio, C C, Heaton, R, Grant, I, Richman, D D, Smith, D M
• Format: Article
• Language: English
• Subjects: Hepatitis C virus; Human immunodeficiency virus
• ISSN: 1355-0284

Background: Before the widespread use of combination antiretroviral therapy (ART), studies indicated that for individuals with AIDS, higher HIV RNA levels in cerebrospinal fluid (CSF) - but not in plasma--were associated with neurocognitive impairment. More recent studies have reported that HIV RNA levels in CSF are not as strongly associated with neurocognitive impairment. It has been suggested that ART lowers CSF HIV RNA levels and therefore lessens the association between CSF HIV RNA levels and neurocognitive function. ART can impact viral dynamics by inhibiting viral replication or by the selection of drug resistant variants that may be less neuropathogenic. We hypothesized that there would be significant differences in CSF HIV RNA levels and neuropsychological (NP) performance between individuals with drug resistance (DR+) and those without drug resistance (DR-). Methods: A comprehensive NP battery was administered to 94 HIV-infected participants at the University of California, San Diego HIV Neurobehavioral Research Center. To assess Global Deficit the results from the NP battery were adjusted for age, education and ethnicity. Higher Global Deficit Scores indicate worse NP performance. Univariate and multivariate analyses included: age, ethnicity, duration of HIV infection, HIV RNA levels in CSF and blood, current and nadir CD4 counts, drug resistance, hepatitis C virus (HCV) serostatus, past and current ART use, ART adherence, methamphetamine use and Global Rating. The Viroseq algorithm and Stanford HIV Resistance Database (April 2007) were used to interpret drug resistance from genotypic data. Results: Logistic regression analysis revealed that the absence of drug resistance (DR-), history of methamphetamine use, lower CD4 count nadir, positive HCV serostatus (HCV+) and no prior ART use were independently associated with worse NP performance. An interaction between HCV status and drug resistance showed that individuals who were HCV+/DR- had worse NP performance than the rest of the study group who were HCV-/DR+, HCV-/DR- or HCV+/DR+. There was a similar interaction with current ART use (ART+) and HCV, which showed that individuals with ART+/HCV+ demonstrated worse NP performance than all other ART and HCV groups. Additionally, for individuals without drug resistance (DR-), higher CSF HIV RNA levels correlated with worse NP performance. However, in individuals with drug resistant HIV (DR+), CSF HIV RNA levels did not correlate with NP performance. D