Publication Abstract Display
Type: Poster
Title: CNS drug distribution and CSF inflammation during suppressive antiretroviral therapy.
Authors: Anderson A, Iudicello J, Kallianpur A, Tolentino K, Ellis R, Grant I, Hulgan T, Letendre S
Date: 02-22-2016
Abstract:Antiretroviral therapy (ART) drugs differ in their distribution into the CNS. Greater estimated ART distribution into the CNS is associated with lower HIV RNA levels in CSF but the relationship with inflammation in the CNS during viral suppression is relatively unknown. The objective of this analysis was to assess this using a training-validation approach with the hypothesis that higher CNS penetration-effectiveness (CPE) values would be associated with lower levels of inflammation-associated biomarkers in CSF. We selected 268 HIV+ adults who were assessed in the CHARTER study and who were taking 3-drug ART; underwent lumbar puncture; and had HIV RNA in plasma and CSF ≤ 50 copies/mL. CXCL10, TNF-α, and IL-6 were quantified in CSF by bead suspension array immunoassay in 2 independent samples: the Training Set (TS, n=144) and the Validation Set (VS, n=124). Data were analyzed using conventional parametric, non-parametric, and multivariable regression methods. The two sets were similar in age, self-reported race/ethnicity, sex, body mass index, AIDS status, current and nadir CD4+ T-cell count, self-reported ART duration, and CPE values. The most common ART regimen was efavirenz-tenofovir-emtricitabine (n=49). All HIV RNA levels were ≤ 50 copies/mL. In both groups, higher CPE values correlated with lower levels of CXCL10 (TS: r=-0.30, p<0.001; VS: r=-0.30, p<0.001) and TNF-α (TS: r=-0.22, p=0.01; VS: r=-0.19, p=0.03) but not IL-6 (TS: r=-0.11, p=0.23; VS: r=0.07, p=0.48). Multivariable models combined data from both groups and adjusted for other statistically significant correlates of each biomarker as well as correlates of CPE. These models confirmed the associations between higher CPE values and either lower CXCL10 (model R2=0.18, p<0.001) or TNF-α levels (model R2=0.05, p=0.04). During suppressive ART, regimens that are estimated to have better distribution into the CNS are associated with less inflammation in CSF, as indicated by levels of CXCL10 and TNF-α. This may reflect better suppression of HIV RNA in the CNS. Estimated ART drug distribution into the CNS did not correlate with IL-6 levels in CSF, which is consistent with findings that IL-6 can both remain elevated during suppressive ART and be associated with HAND (e.g., JAIDS 2015 68:281-8). While cross-validation is a strong approach, longitudinal analyses are needed to further strengthen confidence in these findings.

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