title: Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery.
  
  
  METHODS
  We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, 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
  Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001).
  
  
  CONCLUSIONS
  NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.
authors.affiliation: University of California, San Diego.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.affiliation: University of California, San Diego.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.affiliation: University of California, San Diego.
authors.forename: Reena
authors.initials: R
authors.lastname: Deutsch
authors.affiliation: University of California, San Diego.
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.affiliation: University of California, San Diego.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: University of California, San Diego.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Casaletto
authors.affiliation: University of California, San Diego.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Marquine
authors.affiliation: University of California, San Diego.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Woods
authors.affiliation: University of California, San Diego.
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.affiliation: University of California, San Diego Veterans Affairs San Diego Healthcare System, California.
authors.forename: J Hampton
authors.initials: JH
authors.lastname: Atkinson
authors.affiliation: University of California, San Diego.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Marcotte
authors.affiliation: University of California, San Diego.
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: University of Washington, Seattle.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: University of Washington, Seattle.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: Washington University, St Louis, Missouri.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: University of Texas Medical Branch, Galveston.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: University of California, San Diego.
authors.forename: Ian
authors.initials: I
authors.lastname: Abramson
authors.affiliation: University of California, San Diego.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Gamst
authors.affiliation: University of California, San Diego.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: University of California, San Diego.
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: University of California, San Diego.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000453:epidemiology*; D015897:Comorbidity; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
keywords: HIV; antiretroviral therapy; cognitive change; comorbidities