title: Central nervous system penetration effectiveness of antiretroviral drugs and neuropsychological impairment in the Ontario HIV Treatment Network Cohort Study.
abstract: Since the introduction of combination antiretroviral therapy (cART), the incidence of severe HIV-associated neurocognitive impairment has declined significantly, whereas the prevalence of the milder forms has increased. Studies suggest that better distribution of cART drugs into the CNS may be important in reducing viral replication in the CNS and in reducing HIV-related brain injury. Correlates of neuropsychological (NP) performance were determined in 417 participants of the Ontario HIV Treatment Cohort Study (OCS). All participants were on three cART drugs for at least 90 days prior to assessment. Multiple logistic and linear regression methods were used. Most participants were Caucasian men with mean age of 47 years. About two thirds had a nadir CD4+ T-cell count below 200 cells/μL and 92 % had an undetectable plasma HIV viral load. The median CNS penetration effectiveness (CPE) score was 7. Sixty percent of participants had neuropsychological impairment. Higher CPE values significantly correlated with lower prevalence of impairment in bivariate and multivariate analyses. In this cross-sectional analysis of HIV+ adults who had a low prevalence of comorbidities and were taking three-drug cART regimens, greater estimated distribution of cART drugs into the CNS was associated with better NP performance.
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada. adriana.carvalhal@utoronto.ca.|Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street 17-042, Toronto, ON, Canada, M5B 1W8. adriana.carvalhal@utoronto.ca.
authors.forename: Adriana
authors.initials: A
authors.lastname: Carvalhal
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.affiliation: HIV Neurobehavioural Research Center and Antiretroviral Research Center, University of California San Diego, San Diego, CA, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.affiliation: Sunnybrook Health Sciences Center, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.affiliation: The Ontario HIV Treatment Network, Toronto, Canada.
authors.forename: Tsegaye
authors.initials: T
authors.lastname: Bekele
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Raboud
authors.affiliation: The Ontario HIV Treatment Network, Toronto, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: Ann
authors.initials: A
authors.lastname: Burchell
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.|Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street 17-042, Toronto, ON, Canada, M5B 1W8.|The CIHR Centre for REACH in HIV/AIDS (Research Evidence into Action for Community Health), Toronto, Canada.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Rourke
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D001692:Biological Transport; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D015331:Cohort Studies; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009864:Ontario; D010539:Permeability; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents
keywords: Antiretroviral; CPE; HIV; Neuropsychological impairment