Presence of HIV RNA in cerebrospinal fluid that is undetectable with the ultrasensitive assay.

Type: Poster
Title: Presence of HIV RNA in cerebrospinal fluid that is undetectable with the ultrasensitive assay.
Authors: Letendre S, McClernon D, Benjamin R, Clifford D, Collier A, Gelman B, McArthurJ, McCutchan J, Morgello S, Ellis R, and the CHARTER Group
Date: 02-25-2007
Abstract:Background: The prevalence of HIV Neurocognitive Impairment (HNCI) remains high despite the use of combination antiretroviral therapy (ART). ART can reduce HIV RNA in plasma below 50 c/mL but penetrates into the central nervous system in reduced concentrations, which may allow ongoing replication and injury. The objective of this analysis was to determine the proportion of CSF specimens that have HIV RNA > 2.5 copies (c)/mL among those < 50 c/mL as measured with an ultrasensitive commercial assay. Methods: 125 CSF specimens with HIV RNA levels < 50 c/mL were selected from 125 participants of the CHARTER study, a North American observational cohort. Specimens were selected to vary potentially influential factors, such as HIV RNA in plasma, blood CD4+ counts, HCV serostatus, and neuropsychological (NP) performance. 2 mL CSF specimens were assayed using a modified real-time NucliSens EasyQ HIV-1 assay and software interpolation capable of quantifying HIV RNA to 2.5 c/mL. RNA data were transformed to an ordinal variable (> or ! 2.5 c/mL) and compared with other measures using parametric and non-parametric statistical tests. A CNS Penetration Effectiveness (CPE) Score was calculated as previously described with higher CPE Scores indicating better CNS penetration. Results: 112 subjects (90%) were taking ART; 40 (32%) had HIV RNA in plasma <50 c/mL; the median CD4 count was 421/"L; 89 (71%) had been diagnosed with AIDS. 62 (50%) CSF specimens had HIV RNA > 2.5 c/mL. Detectable levels in CSF were associated with higher HIV RNA in plasma (median 218 vs. 133 c/mL, p=.01) and higher CD4 nadirs (median 180 vs. 101/"L, p=.03). Detectable levels were not associated with leukocyte or erythrocyte counts in CSF, HCV seropositivity, worse NP performance, or duration of regimen. Among the 40 subjects with HIV RNA < 50 c/mL in both CSF and plasma, 17 (42%) had measurable RNA in CSF and this was associated with lower CPE scores (median 1.5 vs. 2.0, p=.01). Twelve subjects who were taking ART had a second study visit. Three of these individuals had undetectable RNA in CSF at their first visit and detectable RNA at the second. CPE Scores were also lower in these 3 subjects than in the other 9 (median .75 vs. 2, p=.02). Conclusions: Nearly half of CSF specimens that had undetectable HIV RNA with an ultrasensitive commercial assay had measurable virus with a more sensitive assay. Lower ART penetration was associated with detectable HIV RNA in CSF in a clinically relevant subgroup and in the small number of longitudinal specimens. These analyses indicate that a substantial proportion of individuals have HIV in CSF despite otherwise successful ART, which may explain the occurrence of HNCI in treated individuals.