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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: 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/?L. 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.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.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.This study was registered with ClinicalTrials.gov on 17 December 2013 (registration number: NCT02018965).

SUBMITTER: Lebouche B

PROVIDER: S-EPMC4283109 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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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.

Lebouché Bertrand B Jenabian Mohammad-Ali MA Singer Joel J Graziani Gina M GM Engler Kim K Trottier Benoit B Thomas Réjean R Brouillette Marie-Josée MJ Routy Jean-Pierre JP

Trials 20141007

<h4>Background</h4>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 oxida ...[more]

PMID: 25293882

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Project description:BACKGROUND:Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. METHODS:A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon's Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). RESULTS:HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p?=?0.03) and be HCV-positive (31%, vs. 23%, p?=?0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120-360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85-294) (p?=?0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p?<?0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p?=?0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p?=?0.02). CONCLUSION:The prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Dataset Information

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.

Publications

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.

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