title: Randomized trial of central nervous system-targeted antiretrovirals for HIV-associated neurocognitive disorder.
abstract: BACKGROUND
  Antiretroviral (ARV) medications differentially penetrate across the blood-brain barrier into central nervous system (CNS) tissues, potentially influencing their effectiveness in treating brain infection.
  
  
  METHODS
  This randomized controlled clinical trial (RCT) called for 120 participants at 5 study sites to be randomized 1:1 to CNS-targeted (CNS-T) or non-CNS-T ART. Entry clinical factors such as ARV experience were balanced across arms using an adaptive randomization approach. The primary outcome, change in neurocognitive performance, was measured as the difference in global deficit score (GDS) from baseline to week 16.
  
  
  RESULTS
  The study was terminated early on the recommendation of its data safety monitoring board on the basis of slow accrual and a low likelihood of detecting a difference in the primary outcome. No safety concerns were identified. Of 326 participants screened, 59 met entry criteria and were randomized. The primary intent-to-treat analysis included 49 participants who completed week 16. These comprised 39 men and 10 women with a mean age of 44 years (SD, 10 years), and median nadir and current CD4(+) T-cell counts of 175 cells/µL and 242 cells/µL, respectively. The proportional improvement in GDS from baseline was nonsignificantly larger (7%; 95% confidence interval [CI], -31% to 62%) in the CNS-T arm than in the non-CNS-T arm, representing a treatment effect size of 0.09 (95% CI, -.48 to .65). Prespecified secondary analysis showed a trend interaction (P = .087), indicating that participants who had baseline plasma virologic suppression may have benefited from CNS-T.
  
  
  CONCLUSIONS
  This study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV-associated neurocognitive disorders. A benefit for a subgroup or small overall benefits could not be excluded. Clinical Trials Registration NCT00624195.
authors.affiliation: Department of Neurosciences.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Susanne
authors.initials: S
authors.lastname: May
authors.forename: Anya
authors.initials: A
authors.lastname: Umlauf
authors.forename: Mariana
authors.initials: M
authors.lastname: Cherner
authors.forename: Chelsea
authors.initials: C
authors.lastname: Sanders
authors.forename: Craig
authors.initials: C
authors.lastname: Ballard
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: Cheryl
authors.initials: C
authors.lastname: Jay
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents
keywords: AIDS; HIV; antiretroviral therapy; cognitive disorders/dementia