title: Does efavirenz replacement improve neurological function in treated HIV infection?
abstract: The contribution of specific antiretroviral drugs to cognitive function in HIV-infected people remains poorly understood. Efavirenz (EFV) may plausibly cause cognitive impairment. The objective of this study was therefore to determine whether chronic EFV therapy is a modifier of neurocognitive and neurometabolic function in the setting of suppressive highly active antiretroviral therapy.
  
  
  
  We performed an open-label phase IV controlled trial. Adult subjects who were stable on suppressive EFV therapy for at least 6 months were switched to ritonavir-boosted lopinavir (LPV/r) with no change in the nucleoside reverse transcriptase inhibitor (NRTI) backbone. The following parameters were assessed before and 10 weeks after therapy switch: cognitive function (by CogState®computerized battery); brain metabolites (by proton magnetic resonance spectroscopy); brain activity [by attentional processing task-based functional magnetic resonance imaging]; and sleep quantity and quality [by sleep diary, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale].
  
  
  
  Sixteen subjects completed the study. Despite most subjects (81%) self-reporting memory problems at baseline, cognitive function, brain metabolites, and brain activity showed no change at 10 weeks after switch. Sleep quality improved on switch off EFV [mean PSQI (standard deviation): EFV, 8.5 (6.5); LPV/r, 5.8 (5.5); mean difference -0.4; 95% confidence interval -6.0 to -0.7].
  
  
  
  This is the first study to assess the effects of chronic EFV therapy on neurological function in a controlled setting. We conclude that EFV withdrawal is unlikely to result in significant modification of neurocognitive function in otherwise stable HIV-infected people.
authors.affiliation: Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.|Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle, UK.
authors.forename: B
authors.identifier: 0000-0002-3101-3512
authors.initials: B
authors.lastname: Payne
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Chadwick
authors.affiliation: Centre for In Vivo Imaging, Newcastle University, Newcastle, UK.
authors.forename: A
authors.initials: A
authors.lastname: Blamire
authors.affiliation: Regional Sleep Service, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
authors.forename: K N
authors.initials: KN
authors.lastname: Anderson
authors.affiliation: Centre for In Vivo Imaging, Newcastle University, Newcastle, UK.
authors.forename: J
authors.initials: J
authors.lastname: Parikh
authors.affiliation: Newcastle Clinical Trials Unit, Newcastle University, Newcastle, UK.
authors.forename: J
authors.initials: J
authors.lastname: Qian
authors.affiliation: Newcastle Clinical Trials Unit, Newcastle University, Newcastle, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Hynes
authors.affiliation: Newcastle Clinical Trials Unit, Newcastle University, Newcastle, UK.
authors.forename: J
authors.initials: J
authors.lastname: Wilkinson
authors.affiliation: Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Price
mesh_terms: D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D001923:Brain Chemistry; D003071:Cognition / Q000187:drug effects*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066244:Proton Magnetic Resonance Spectroscopy; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir
keywords: 
  HIV
  ; cognitive impairment; efavirenz; functional magnetic resonance imaging; magnetic resonance spectroscopy