Lower CSAR are associated with global neurocognitive impairment in antiretroviral-treated people with HIV.

Type: Poster
Title: Lower CSAR are associated with global neurocognitive impairment in antiretroviral-treated people with HIV.
Authors: Letendre S, Croteau D, Ellis R, Clifford D, Gelman B, Marra C, McArthur J, McCutchan A, Simpson D, Grant I, and the CHARTER Group
Date: 02-28-2011
Abstract:Background: Albumin is a large molecule that is typically excluded from the central nervous system (CNS) by the blood-brain barrier (BBB). Among untreated people with HIV, increased BBB permeability, as reflected by higher CSF-serum albumin ratios (CSARs), could allow HIV and neurotoxins greater access to the CNS. Among treated people, increased BBB permeability could also allow higher concentrations of antiretrovirals to reach the CNS. Few HIV studies have compared CSARs to disease or neurocognitive characteristics in treated individuals, which was the objective of this analysis. Methods: Albumin was measured in CSF (mg/dL) and plasma (g/dL) specimens from 233 treated HIV+ participants (pts) of the CHARTER cohort by clinical laboratories. All subjects underwent standardized neurocognitive testing. HIV RNA levels were measured by commercial RT-PCR. Data were analyzed using standard statistical procedures, including correlation coefficients, t-tests, receiver operator characteristic curves, and multivariable regression. Neurocognitive analyses were limited to subjects without confounding comorbidities. Results: Pts were mostly middle-aged (median 44 yr) men (78%) with AIDS (76%). 44% were white and 43% were black. HIV RNA were ≤ 50 c/mL in 56% of PL and 82% of CSF specimens. Median current and nadir CD4+ cell counts were 418 and 110. 30% were HCV seropositive. Median CSAR was 4 (IQR 3.2, 5.1). Higher CSARs were associated with older age (r = 0.19, p = 0.004), shorter durations of ART (-0.14, p = 0.03), HCV seronegativity (t = -2.0, p = 0.04), male gender (t = 3.7, p < 0.001), and white ethnicity (6 = 3.2, p = 0.001). All associations were present on multivariable analysis, except HCV serostatus. Untransformed CSAR values were not associated with global neurocognitive performance but subjects who had CSARs below 3.5 had twice the odds of having global impairment (63% vs. 44%, OR = 2.1, p = 0.01). Multivariable analysis identified that global impairment was associated with CSARs below 3.5 and older age (R2 = 0.06, p < 0.001). Conclusions: CSARs in people with HIV vary based on age, gender, ethnicity, and duration of ART. In this group of treated individuals, global neurocognitive impairment was associated with lower CSARs, suggesting that when the BBB restricts large molecules, such as albumin from the CNS, it may also restrict beneficial molecules, such as antiretroviral drugs.