| Publication Abstract Display | | Type: Published Abstract | | Title: Correlates of CSF Viral Loads in 1,221 volunteers of the CHARTER cohort. | | Authors: Letendre SL, FitzSimons C, Ellis RJ, Clifford D, Collier AC, Gelman B, Marra C, McArthur J, McCutchan JA, Morgello S, Simpson D, Vaida F, Heaton R, Grant I, and the CHARTER Group | | Year: 2010 | | Publication: 17th Conference on Retroviruses and Opportunistic Infections | | Volume: Issue: Pages: | | Abstract:Background: A biomarker is needed for HIV-associated neurocognitive disorders, which are common despite potent antiretroviral therapy (ART). Conflicting data exist about the value of CSF viral loads (VL). Since some prior analyses were constrained by limited size or cohort composition, we measured CSF VLs in a large, diverse cohort and described their demographic and clinical correlates.
Methods: Cross-sectional analyses of 1,221 HIV+ pts of CHARTER, a 6-center, US-based cohort. Lower limit of quantitation (LLQ) of HIV VL assay was 50 c/mL. Non-adherence was estimated by self-report of taking < 95% of ART doses in 4 days. ART penetration was estimated by the published CPE method and by a recently revised version. Univariate analyses correlated CSF VLs with other study data. Multivariable analyses used linear and logistic regression methods.
Results: Median CSF VL was the LLQ with 34% of values being above the LLQ (detectable). CSF VLs were strongly influenced by ART use: 76% of 379 pts not taking ART had a CSF VL > LLQ vs. 16% of the 842 taking ART. Not taking ART: Higher CSF VLs were associated with higher plasma VLs (r = 0.60, p < 0.0001), lower CD4+ counts (r = -0.22, p < 0.0001), lower nadir CD4+ counts (r = -0.09, p = 0.05), older age (r = 0.09, p = 0.06), white ethnicity (t = 1.8, p = 0.07), and male gender (t = 1.7, p = 0.09). Multivariable analysis identified that higher CSF VLs were associated with higher plasma VLs and older age (R2 = 0.38, p < 0.0001). Taking ART: Detectable CSF VLs were associated with higher plasma VLs (R2 = 0.33, p < 0.0001), white ethnicity (OR = 2.5, p < 0.0001), lower CD4+ cell counts (R2 = 0.05, p < 0.0001), more prior antiretrovirals (R2 = 0.01, p = 0.003), shorter duration of current regimen (R2 = 0.02, p = 0.0001), non-adherence (OR = 2.8, p = 0.0001), older age (R2 = 0.01, p = 0.03), and worse revised CPE ranks (OR = 1.7, p = 0.007). Multivariable analysis identified that detectable CSF VLs were associated with higher plasma VLs, white ethnicity, non-adherence, and worse revised CPE ranks (R2 = 0.39, p < 0.0001).
Conclusions: Plasma VL was the strongest correlate of CSF VL, emphasizing the importance of systemic HIV suppression for control of HIV in the nervous system. Without ART, higher CSF VLs also correlated with older age. With ART, detectable CSF VLs were associated with worse adherence, worse estimated penetration, and white ethnicity. The mechanisms by which age and ethnicity influence CSF VL are unknown. |
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