Neurocognitive change in the era of HIV combination antiretroviral therapy: A CHARTER Study.

Type: Poster
Title: Neurocognitive change in the era of HIV combination antiretroviral therapy: A CHARTER Study.
Authors: Heaton R, Franklin D, Deutsch R, Letendre S, Ellis RJ, Casaletto K, Marquine M, Woods SP, Vaida F, Atkinson JH, Marcotte TD, McCutchan JA, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Smith DM, Grant I, for the CHARTER Group
Year: 2014
Conference: International AIDS Conference

Background: HIV-associated neurocognitive disorder (HAND) is not an immutable diagnosis and can show variable clinical trajectories. Previous longitudinal studies of HAND have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial thereby limiting our understanding of neurocognitive decline and recovery.

Methods: We investigated the incidence and predictors of NC change over 16 to 72 (mean 35) months in 436 HIV-infected participants in the CHARTER cohort. Comprehensive laboratory, neuromedical and NC assessments were obtained every 6 months. Regression-based norms for NC change were used to generate overall change status (decline vs. stable vs. improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change.

Results: 99 participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analysis, Hispanic ethnicity (vs. non-Hispanic: RR (95% CI) 2.16 (1.29, 3.61)); confounded comorbidity status (vs. incidental: 2.11 (1.22, 3.66)); being off ART (vs. on ART: 1.88 (1.22, 2.90)); having low albumin (vs. 1 unit higher: 1.59 (1.00, 2.53)) and low hematocrit (vs. 1 unit higher: 1.08 (1.03, 1.13)); and having a lifetime methamphetamine use diagnosis (vs. none: 1.88 (1.17, 3.03)) and more depressive symptoms (vs. 1 unit lower: 1.02 (1.00, 1.04)) were associated with earlier time to NC decline (overall model p<0.0001). The multivariable combination of predictors of improvement included higher education (vs. 1 year less: 1.12 (1.02, 1.23)); ART regimen switch (vs. no switch: 1.56 (0.95, 2.56)); lower AST (vs.1 unit higher: 1.01 (1.00, 1.03)); and no lifetime major depressive disorder (vs. positive history: 1.68 (1.05, 2.71)) (overall model p=0.0014).

Conclusions: NC change is common in HIV infection with 23% declining and 17% improving. Our finding of significant, time-dependent clinical and biological predictors of NC change, suggest that the observed associations may be clinically meaningful. Further, they suggest that consistent use of ART to maintain virologic control and avoid serious immunosuppression may have beneficial long-term effects in protecting the CNS and improving NC outcomes. Finally, increased comorbidity burden and factors associated with Hispanic ethnicity deserve more attention in clinical care of HIV+ individuals.