title: Select resistance-associated mutations in blood are associated with lower CSF viral loads and better neuropsychological performance.
abstract: BACKGROUND
  When antiretroviral therapy does not fully suppress HIV replication, suboptimal levels of antiretrovirals can select for antiretroviral resistant variants of HIV. These variants may exhibit reduced replication capacity and result in lower viral loads in blood. Our study evaluated whether antiretroviral resistance was associated with viral loads in the cerebrospinal fluid (CSF) and better neuropsychological (NP) performance.
  
  
  METHODS
  We enrolled 94 participants and each participant underwent a comprehensive neuromedical evaluation that used structured clinical assessments of medical history, ART and other medication use, comprehensive NP testing, and neurological and general physical signs of disease. Blood was collected by venipuncture, and all participants were offered lumbar puncture. Univariate and multivariate statistical methods were used to analyze the relationship between antiretroviral resistance, blood and CSF HIV RNA levels, substance use, and NP performance.
  
  
  RESULTS
  Antiretroviral resistance, detected in blood, was associated with lower CSF viral loads (p<0.01) and better NP performance (p=0.04) in multivariate analyses, independent of past and current ARV use and blood viral loads (model: p<0.01). However, HIV RNA levels in CSF did not independently correlate with NP performance. Low viral loads in the CSF limited our ability to investigate the relationship between antiretroviral resistance detected in CSF and NP performance.
  
  
  CONCLUSIONS
  Even in the absence of ART, antiretroviral resistance-associated mutations correlate with better NP performance possibly because these mutations reflect reduced neurovirulence compared with wild-type HIV.
authors.affiliation: University of California, San Diego, La Jolla, CA 92037, USA. ghightow@ucsd.edu
authors.forename: George K
authors.initials: GK
authors.lastname: Hightower
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Mariana
authors.initials: M
authors.lastname: Cherner
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Gibson
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Wolfson
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Gamst
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Ignacio
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology* / Q000821:virology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008694:Methamphetamine; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D012189:Retrospective Studies; D019966:Substance-Related Disorders / Q000150:complications; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D008694:Methamphetamine