title: Resumption of HIV replication is associated with monocyte/macrophage derived cytokine and chemokine changes: results from a large international clinical trial.
abstract: BACKGROUND
  There is increasing interest in the role of immune activation and inflammation in HIV disease, but data on direct effects of HIV replication on immune cell activation are limited.
  
  
  METHODS
  High sensitivity multiplex bead array assays (MBAAs) were used to measure changes in plasma cytokines and chemokines [interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-12p70, IL-17, tumor necrosis factor-α (TNFα), interferon-γ, granulocyte macrophage colony-stimulating factor, IL-4, IL-5, IL-10, IL-13, CXCL10] from randomization (month 0) to month 2 in a random sample of 200 patients from both the drug conservation (DC) and viral suppression (VS) arms of the Strategies for Management of Antiretroviral Therapy (SMART) trial. IL-6 was also measured by ELISA. Data were evaluated using nonparametric correlation and censored parametric analysis of covariance and associations were declared as statistically significant when the Bonferroni-adjusted P-value was less than 0.003.
  
  
  RESULTS
  Compared with the VS arm, significant increases were seen in the DC arm for TNFα (+0.34 log(e) pg/ml, P = 0.0001), IL-10 (+0.33 log(e) pg/ml, P = 0.00001) and CXCL10 (+0.66 log(e) pg/ml, P = 0.00001). IL-6 ELISA poorly correlated with IL-6 MBAA (Spearman's rho = 0.29, P = 0.0001).
  
  
  CONCLUSIONS
  Resumption of HIV replication after ceasing antiretroviral therapy is associated predominantly with an increase of monocyte/macrophage-derived cytokines. Measurement of IL-6 levels may be affected by assay method and this should be considered in future studies of biomarkers.
authors.affiliation: HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Royal Free Campus, University College London, London, UK. a.cozzi-lepri@ucl.ac.uk
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
authors.forename: John
authors.initials: J
authors.lastname: Baxter
authors.forename: Pablo
authors.initials: P
authors.lastname: Okhuysen
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology / Q000502:physiology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D016173:Macrophage Colony-Stimulating Factor