| Publication Abstract Display | | Type: Published Abstract | | Title: ART resistance influences CSF HIV RNA levels and neuropsychological performance in HIV-infected individuals. | | Authors: Hightower G, Letendre S, Cherner M, Gibson S, Ellis R, Ignacio C, Heaton R, Grant I, Richman D, Smith D, and the HNRC Group | | Year: 2008 | | Publication: 15th Conference on Retroviruses and Opportunistic Infections | | Volume: Issue: Pages: | | Abstract:Background: ART can significantly lower viral replication in the central nervous system (CNS) and improve neuropsychological performance; however, this effect can vary significantly. The influence of ART resistance on viral dynamics in the CNS may in part explain this variability. Our objectives were to determine if there is an association between ART resistance and neuropsychological performance and if ART resistance changes the association between neuropsychological impairment and cerebrospinal fluid (CSF) HIV RNA levels.
Methods: A comprehensive neuropsychological battery with scores adjusted for age, education, sex, and ethnicity, was administered to 94 HIV+ individuals enrolled in the NeuroAIDS Effects of Methamphetamine project in San Diego, California. Neuropsychological performance was summarized as the global rating, which adjusts for age, education, and ethnicity. Univariate and multivariate methods were used to compare ART resistance to HIV RNA levels in CSF and blood, current and nadir CD4 counts, ART use, neuropsychological performance, recent methamphetamine dependence, and other demographic and disease-related factors.
Results: The median blood plasma HIV RNA and CD4 count were 4.7 log10 copies/mL and 319 cells/µL. CSF HIV RNA measurements were obtained for 69 of the 94 subjects and the median level was 2.9 log10 copies/mL. ART resistance was detected in 48 of the 94 participants, and the most common resistance associated mutations were 184V/I (20%) and K103N (15%). Even after adjusting for other factors in multivariate analyses, lower CSF HIV RNA levels were associated with ART resistance (p = 0.05) and lower plasma HIV RNA (p <0.001). For individuals with no detectable resistance, there was a significant correlation between higher CSF HIV RNA levels and worse neuropsychological performance (ρ = 0.41, p = 0.03), but when resistance was detectable, higher CSF HIV RNA levels did not correlate with worse NP performance (ρ = 0.07, p = 0.78).
Conclusions: Resistance was associated with lower CSF HIV RNA levels, and this effect was independent of current ART use. In addition, the relationship between neuropsychological performance and CSF HIV RNA levels differed based on the presence or absence ART resistance, which may explain why studies conducted prior to the widespread use of ART identified a correlation between neuropsychological impairment and CSF HIV RNA levels, while more recent studies have not. |
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