title: Changes in Cognitive Function Over 96 Weeks in Naive Patients Randomized to Darunavir-Ritonavir Plus Either Raltegravir or Tenofovir-Emtricitabine: A Substudy of the NEAT001/ANRS143 Trial.
abstract: BACKGROUND
  Improvements in cognitive function are described after initiation of combination antiretroviral therapy (cART), with sparse data on differences between cART strategies.
  
  
  METHODS
  We assessed changes in cognition, over 96 weeks, in therapy-naive HIV-positive adults randomized to darunavir/ritonavir (800/100 mg once daily) with either raltegravir (400 mg twice daily, Arm1) or tenofovir/emtricitabine (245/200 mg once daily, Arm2). Seven cognitive tests were administered at baseline and week (W) 96. Changes from baseline in individual cognitive test scores and composite score (NPZ) were assessed. Comparisons between treatment arms were by intention to treat and associations with immunological and virological parameters by regression models.
  
  
  RESULTS
  Of 343 subjects enrolled, 208 completed the W96 cognitive assessment. Baseline median (interquartile range) CD4 count and plasma HIV RNA were 348 (282-398) cells per microliter and 4.7 (4.2-5.1) log10 copies per milliliter, respectively. At W96, numbers with plasma HIV RNA undetectable and remaining on randomized cART were 85 (92%) and 110 (96%), and 84 (90%) and 107 (93%) in Arm1 and Arm2, respectively. Overall performance significantly improved by W96 in 5 of 7 individual tests and in NPZ. Mean changes in NPZ were 0.28 versus 0.21 for Arm1 and 2, respectively (P = 0.37). No statistically significant differences between study treatment arms were observed in individual cognitive domains apart from attention (greater improvement in Arm1, P = 0.0499). At W96, NPZ score increase was associated with increase in CD4 (P = 0.001) but not HIV RNA area under curve (P = 0.60).
  
  
  CONCLUSIONS
  Subsequent to the initiation of cART, immunological recovery rather than type of antiretroviral therapy is the major driver of changes in cognitive function.
authors.affiliation: *Department of Medicine, Imperial College London, London, United Kingdom; †MRC Clinical Trials Unit, UCL, London, United Kingdom; ‡Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy; §Univ Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; ‖Infectious Diseases Department, CHD Vendee, La Roche sur Yon, France; ¶Division of Infectious Diseases, Saint Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium; #Infectious Diseases Department, Gui de Chauliac Hospital, Montpellier, France; **North Bristol NHS Trust, Bristol, United Kingdom; ††Department of Health Sciences, Clinic of Infectious and Tropical Diseases, San Paolo University Hospital, Milan, Italy; ‡‡Infectious Diseases Department, The Hospital Clinic, Institut d'investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; §§Department of Infectious Diseases and Rheumatology, Centre for Health and Infectious Disease Research (CHIP), Rigshospitalet, Copenhagen, Denmark; ‖‖Chelea and Westminster NHS Foundation Trust, London, United Kingdom; ¶¶CMIT, Paris, France; and ##CHU de Bordeaux, Pole de sante publique, and CIC1401-EC (Clinical Epidemiology), Bordeaux, France.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Helene
authors.initials: H
authors.lastname: Amieva
authors.forename: Philippe
authors.initials: P
authors.lastname: Perré
authors.forename: Stephane
authors.initials: S
authors.lastname: De Wit
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Mark
authors.initials: M
authors.lastname: Gompels
authors.forename: Antonella
authors.initials: A
authors.lastname: dʼArminio Monforte
authors.forename: Jose-Maria
authors.initials: JM
authors.lastname: Gatell
authors.forename: Jesper
authors.initials: J
authors.lastname: Grarup
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Laura
authors.initials: L
authors.lastname: Richert
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000473:pathology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003071:Cognition / Q000502:physiology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents