title: Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial.
abstract: To determine whether treatment with ritonavir-boosted protease inhibitor (PI) monotherapy is associated with detrimental effects on neurocognitive function or brain imaging markers compared to standard antiretroviral therapy (ART).
  
  
  
  Neuropsychological assessment and brain magnetic resonance imaging were performed at the last study visit in a subset of participants randomized to PI monotherapy (PI-mono group) or ongoing triple ART (OT group) in the PIVOT trial. We calculated a global z-score (NPZ-7) from the average of the individual test z-scores and the proportion of participants with symptomatic neurocognitive impairment (score >1 standard deviation below normative means in ≥2 cognitive domains and neurocognitive symptoms). In a subgroup, white matter hyperintensities, bicaudate index, global cortical (GCA) and medial temporal lobe atrophy scores and single voxel (basal ganglia) N-acetylaspartate (NAA)/Choline, NAA/Creatine and myo-inositol/Creatine ratios were measured.
  
  
  
  146 participants (75 PI-mono) had neurocognitive testing (median time after randomization 3.8 years), of whom 78 were imaged. We found no difference between arms in NPZ-7 score (median -0.4 (interquartile range [IQR] = -0.7; 0.1) vs -0.3 (IQR = -0.7; 0.3) for the PI-mono and OT groups respectively, P = .28), the proportion with symptomatic neurocognitive impairment (13% and 18% in the PI-mono and OT groups respectively; P = .41), or any of the neuroimaging variables (P > .05). Symptomatic neurocognitive impairment was associated with higher GCA score (OR = 6.2 per additional score; 95% confidence interval, 1.7-22.3 P = .005) but no other imaging variables.
  
  
  
  Based on a comprehensive neuropsychological assessment and brain imaging, PI monotherapy does not increase the risk of neurocognitive impairment in stable human immunodeficiency virus-positive patients.
authors.affiliation: MRC-Clinical Trials Unit at University College London (UCL) UCL Research Department of Infection and Population Health.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arenas-Pinto
authors.affiliation: MRC-Clinical Trials Unit at University College London (UCL).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.affiliation: Neuroradiology Academic Unit, UCL Department of Brain Repair & Rehabilitation, Institute of Neurology.
authors.forename: Hans Rolf
authors.initials: HR
authors.lastname: Jäger
authors.affiliation: UCL Research Department of Infection and Population Health.
authors.forename: Lewis
authors.initials: L
authors.lastname: Haddow
authors.affiliation: Brighton and Sussex University Hospitals NHS Trust, Brighton.
authors.forename: Amanda
authors.initials: A
authors.lastname: Clarke
authors.affiliation: Royal Free Hospital, London.
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Royal Berkshire Hospital, Reading.
authors.forename: Fabian
authors.initials: F
authors.lastname: Chen
authors.affiliation: Imperial College London, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.affiliation: Neuroradiology Academic Unit, UCL Department of Brain Repair & Rehabilitation, Institute of Neurology.
authors.forename: Claudia
authors.initials: C
authors.lastname: Godi
authors.affiliation: Neuroradiology Academic Unit, UCL Department of Brain Repair & Rehabilitation, Institute of Neurology.
authors.forename: Steffi
authors.initials: S
authors.lastname: Thust
authors.affiliation: UCL Research Department of Infection and Population Health.
authors.forename: Rita
authors.initials: R
authors.lastname: Trombin
authors.affiliation: MRC-Clinical Trials Unit at University College London (UCL).
authors.forename: Janet
authors.initials: J
authors.lastname: Cairns
authors.affiliation: NMR Research Unit, UCL Department of Neuroinflammation, Queen Square MS Centre, Institute of Neurology, London.
authors.forename: Bhavana S
authors.initials: BS
authors.lastname: Solanky
authors.affiliation: Neuroradiology Academic Unit, UCL Department of Brain Repair & Rehabilitation, Institute of Neurology.
authors.forename: Xavier
authors.initials: X
authors.lastname: Golay
authors.affiliation: MRC-Clinical Trials Unit at University College London (UCL) Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Paton
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019965:Neurocognitive Disorders / Q000139:chemically induced / Q000821:virology*; D059906:Neuroimaging; D009483:Neuropsychological Tests; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D017320:HIV Protease Inhibitors; D019438:Ritonavir
keywords: HIV; monotherapy; neurocognitive function; neuroimaging; protease inhibitor