title: The role of extended-release niacin on immune activation and neurocognition in HIV-infected patients treated with antiretroviral therapy - CTN PT006: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Approximately 30% of HIV-1-infected patients receiving antiretroviral therapy who achieve virologic control have unsatisfactory immune reconstitution, with CD4+ T-cell counts persistently below 350 cells/μL. These patients are at elevated risk for clinical progression to AIDS and non-AIDS events. CD4+ T-cell depletion following infection and persistent immune activation can partially explain this low CD4+ T-cell recovery. Recent data suggest a link between the tryptophan oxidation pathway, immune activation and HIV disease progression based on overstimulation of the tryptophan oxidation pathway by HIV antigens and by interferon-gamma. This overstimulation reduces levels of circulating tryptophan, resulting in inflammation which has been implicated in the development of neurocognitive dysfunction. Niacin (vitamin B3) is able to control the excess tryptophan oxidation, correcting tryptophan depletion, and therefore represents an interesting strategy to improve CD4 recovery.We aim to design a crossover proof-of-concept study to assess supplementation with an extended-release form of niacin (Niaspan FCT™) in combination with antiretroviral therapy, compared to antiretroviral therapy alone, on T-cell immune activation as defined by changes in the percentage of CD8+ CD38+ HLA-DR+ T-cells.
  
  
  METHODS
  This randomized, open-label, interventional crossover study with an immediate versus deferred use of Niaspan FCT for 24 weeks will assess its ability to reduce immune activation and thus increase CD4 recovery in 20 HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression. A substudy evaluating neurocognitive function will also be conducted.
  
  
  CONCLUSIONS
  This randomized trial will provide an opportunity to evaluate the potential benefit of oral extended-release niacin, a drug that can indirectly increase tryptophan, to reduce immune activation and in turn increase CD4+ T-cell recovery. The study will also allow for the evaluation of the impact of Niaspan FCT on neurocognitive function in HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression.
  
  
  BACKGROUND
  This study was registered with ClinicalTrials.gov on 17 December 2013 (registration number: NCT02018965).
authors.affiliation: Chronic Viral Illness Service, Montreal Chest Institute, McGill University Health Centre, 3650 Saint Urbain St,, Montreal, QC H2X 2P4, Canada. bertrand.lebouche@mcgill.ca.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lebouché
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
authors.forename: Gina M
authors.initials: GM
authors.lastname: Graziani
authors.forename: Kim
authors.initials: K
authors.lastname: Engler
authors.forename: Benoit
authors.initials: B
authors.lastname: Trottier
authors.forename: Réjean
authors.initials: R
authors.lastname: Thomas
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Brouillette
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D002985:Clinical Protocols; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000523:psychology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000276:immunology; D009525:Niacin / Q000627:therapeutic use*; D011792:Quebec; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D009525:Niacin; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1