title: Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions.
abstract: OBJECTIVE
  The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.
  
  
  METHODS
  HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.
  
  
  RESULTS
  A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58).
  
  
  CONCLUSIONS
  We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.
authors.affiliation: Authors' affiliations are listed at the end of the article. ecanigli@hsph.harvard.edu.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Caniglia
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Cain
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Amy
authors.initials: A
authors.lastname: Justice
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Janet
authors.initials: J
authors.lastname: Tate
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Roger
authors.initials: R
authors.lastname: Logan
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
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authors.forename: Alan
authors.initials: A
authors.lastname: Winston
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authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Ashley
authors.initials: A
authors.lastname: Olson
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Arribas
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Jorge
authors.initials: J
authors.lastname: del Romero
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Gilles
authors.initials: G
authors.lastname: Wandeler
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Georgia
authors.initials: G
authors.lastname: Vourli
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Skoutelis
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lanoy
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Jacques
authors.initials: J
authors.lastname: Gasnault
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
mesh_terms: D015526:AIDS Dementia Complex / Q000453:epidemiology*; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D019090:Case Management; D002490:Central Nervous System / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents