title: Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa: Analyses From the EARNEST Trial.
abstract: OBJECTIVE
  To assess neurocognitive function at the first-line antiretroviral therapy failure and change on the second-line therapy.
  
  
  METHODS
  Randomized controlled trial was conducted in 5 sub-Saharan African countries.
  
  
  METHODS
  Patients failing the first-line therapy according to WHO criteria after >12 months on non-nucleoside reverse transcriptase inhibitors-based regimens were randomized to the second-line therapy (open-label) with lopinavir/ritonavir (400 mg/100 mg twice daily) plus either 2-3 clinician-selected nucleoside reverse transcriptase inhibitors, raltegravir, or as monotherapy after 12-week induction with raltegravir. Neurocognitive function was tested at baseline, weeks 48 and 96 using color trails tests 1 and 2, and the Grooved Pegboard test. Test results were converted to an average of the 3 individual test z-scores.
  
  
  RESULTS
  A total of 1036 patients (90% of those >18 years enrolled at 13 evaluable sites) had valid baseline tests (58% women, median: 38 years, viral load: 65,000 copies per milliliter, CD4 count: 73 cells per cubic millimeter). Mean (SD) baseline z-score was -2.96 (1.74); lower baseline z-scores were independently associated with older age, lower body weight, higher viral load, lower hemoglobin, less education, fewer weekly working hours, previous central nervous system disease, and taking fluconazole (P < 0.05 in multivariable model). Z-score was increased by mean (SE) of +1.23 (0.04) after 96 weeks on the second-line therapy (P < 0.001; n = 915 evaluable), with no evidence of difference between the treatment arms (P = 0.35).
  
  
  CONCLUSIONS
  Patients in sub-Saharan Africa failing the first-line therapy had low neurocognitive function test scores, but performance improved on the second-line therapy. Regimens with more central nervous system-penetrating drugs did not enhance neurocognitive recovery indicating this need not be a primary consideration in choosing a second-line regimen.
authors.affiliation: *Research Program, Infectious Diseases Institute, Makerere University, Kampala, Uganda; †MRC Clinical Trials Unit at UCL, London, United Kingdom; ‡University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe; §Research Department, Joint Clinical Research Centre (JCRC), Kampala, Uganda; ‖Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; ¶Dignitas International, Zomba, Malawi; #Department of Medicine, St. Francis of Nsambya Hospital, Kampala, Uganda; **Clinical Research Centre, Moi University School of Medicine, Eldoret, Kenya; and ††Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thompson
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.forename: Dinah
authors.initials: D
authors.lastname: Tumukunde
authors.forename: Joep J
authors.initials: JJ
authors.lastname: van Oosterhout
authors.forename: Raymond
authors.initials: R
authors.lastname: Mwebaze
authors.forename: Anne
authors.initials: A
authors.lastname: Hoppe
authors.forename: James
authors.initials: J
authors.lastname: Abach
authors.forename: Charles
authors.initials: C
authors.lastname: Kwobah
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arenas-Pinto
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Walker
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Paton
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003071:Cognition / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019965:Neurocognitive Disorders / Q000188:drug therapy / Q000209:etiology*; D000068898:Raltegravir Potassium / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D000068898:Raltegravir Potassium; D019438:Ritonavir