Publication Abstract Display
Type: Poster
Title: Correlates of time-to-loss-of-viral-response in CSF and plasma in the CHARTER Cohort.
Authors: Letendre SL, Ellis RJ, Deutsch R, Clifford D, Collier AC, Gelman B, Marra C, McArthur J, McCutchan JA, Morgello S, Simpson D, Heaton R, Grant I, and the CHARTER Group
Date: 02-16-2010
Abstract:Background: No studies have determined the correlates of the time-to-loss-of-HIV suppression in CSF. To address this, we determined the time-to-loss-of HIV suppression in a large, longitudinal cohort and compared the results in CSF and plasma. Methods: Longitudinal analysis of HIV+ pts of CHARTER, a 6-center, US-based cohort, who were taking antiretroviral therapy (ART), were suppressed below the lower limit of quantitation (LLQ, 50 c/mL) in CSF (n = 346) or plasma (n = 225) at their initial visit, and had at least two semiannual visits. Kaplan-Meier estimates of time-to-loss-of-viral response (TLVR), defined as a VL > 50 c/mL, were calculated for dichotomized demographic, clinical, and neuropsychological (NP) variables. Baseline variables that were significant at the 10% significance level (Wilcoxon) were analyzed by multivariable Cox proportional hazards models and likelihood ratio tests. Results: Median duration of ART at the initial visit was 11.1 months in the CSF analysis and 13.0 months in the plasma analysis. In the CSF analysis, 67 events (19%) occurred over a median 9.3 months and 279 (81%) maintained suppression over a median 20.3 months. Baseline predictors of shorter TLVR in CSF were detectable HIV VL in plasma, CD4+ counts < 200, age ≤ 43 years, black ethnicity, protease inhibitor (PI) use, and absence of antidepressant (AD) use. Pts who were NP impaired and reported non-adherence also had shorter TLVR in CSF. Multivariable analysis confirmed that each variable - other than plasma VL and AD use - contributed to the duration of TLVR (model p < 0.0001). In the plasma analysis, 82 events (36%) occurred over a median of 9.3 months and 143 (64%) maintained suppression over a median of 18.0 months. Baseline predictors of TLVR in plasma were CD4+ counts < 200, age ≤ 43 years, black ethnicity, and global NP impairment. Multivariable analysis confirmed that each of these variables were associated with shorter TLVR in plasma (model p < 0.0001). Conclusions: A substantial minority lost their viral response within a year of entering this cohort study. Predictors of shorter TLVR were similar in CSF and blood except that use of PIs and non-adherence were only associated with shorter TLVR in CSF. Although this cohort-based analysis has an important limitation – initiation of ART was not observed as in a clinical trial – the findings identify that NP impairment is associated with shorter viral responses in CSF and plasma.

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