| Publication Abstract Display | | Type: Published Abstract | | Title: Discordance in ARV resistance profiles between blood and cerebrospinal fluid is associated with current ARV use. | | Authors: Hightower G, Letendre S, Gibson S, Ellis R, Ignacio C, Heaton R, Grant I, Richman D, Smith D | | Year: 2009 | | Publication: 16th Conference on Retrovirusese and Opportunistic Infections | | Volume: Issue: Pages: | | Abstract:Background: The central nervous system and blood can act as separate virologic compartments, allowing for the independent evolution of HIV with consequences for HIV replication and ARV resistance. We set to determine if differences in resistance profiles of HIV derived from paired blood and cerebrospinal fluid (CSF) were associated with differences in neuropsychological performances and viral loads in blood and CSF.
Methods: A total of 27 HIV-infected individuals underwent an assessment of medical and ARV history, and a comprehensive neuropsychological battery, adjusted for age, education, and ethnicity. HIV RNA was extracted and measured from paired blood and CSF samples, and the reverse transcriptase coding region was amplified and sequenced; resistance-associated mutations were interpreted by the Stanford HIV Drug Resistance Database. resistance associated mutations discordance was defined as ³1 resistance-associated mutation in blood not present in CSF or visa-versa. Analyses were performed with Fisher’s exact and Wilcoxon rank tests and included HIV RNA levels in CSF and blood, current and nadir CD4, resistance-associated mutations, and current ARV use. Based on results, multivariate analyses were not pursued.
Results: Participants were mostly Caucasian men in their mid 30s; 22% were receiving ARV at the time of sampling. The median blood and CSF HIV RNA levels were 4.7 and 3.3 log10 copies/mL, and current and nadir CD4 count of 308 and 214 cells/µL. Resistance-associated mutations were detected in 59% participants, and the most common were at residues 69 (31%), 103 (31%), and 184 (25%). Of participants with resistance-associated mutations, 81% had discordance of resistance-associated mutations between blood and CSF. Discordance was associated with current ARV use (p = 0.07). Blood and CSF HIV RNA levels were not associated with presence of resistance-associated mutations in either compartment, neuropsychological performance, current and nadir CD4 count, or current ARV use.
Conclusions: This investigation was nested in a well-characterized but relatively small study cohort; however, discordance of resistance-associated mutations did not appear to influence CSF or blood HIV RNA levels or neuropsychological performance. Discordance, however, was associated with ARV use. When ART fails to maximally suppress viral replication, the differential selection of resistance associated mutations in CSF and blood compartments most likely results from differential ARV penetration. |
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