title: Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.
abstract: OBJECTIVE
  The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study.
  
  
  METHODS
  Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations.
  
  
  RESULTS
  The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death.
  
  
  CONCLUSIONS
  Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.
authors.affiliation: Imperial College, Norfolk Place, London, UK. l.garvey@imperial.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Garvey
authors.forename: A
authors.initials: A
authors.lastname: Winston
authors.forename: J
authors.initials: J
authors.lastname: Walsh
authors.forename: F
authors.initials: F
authors.lastname: Post
authors.forename: K
authors.initials: K
authors.lastname: Porter
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: C
authors.initials: C
authors.lastname: Leen
authors.forename: D
authors.initials: D
authors.lastname: Pillay
authors.forename: T
authors.initials: T
authors.lastname: Hill
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Gilson
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Easterbrook
authors.forename: L
authors.initials: L
authors.lastname: Bansi
authors.forename: C
authors.initials: C
authors.lastname: Orkin
authors.forename: J
authors.initials: J
authors.lastname: Ainsworth
authors.forename: A
authors.initials: A
authors.lastname: Palfreeman
authors.forename: M
authors.initials: M
authors.lastname: Gompels
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: C A
authors.initials: CA
authors.lastname: Sabin
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000209:etiology / Q000821:virology; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens