Resumption of HIV replication is associated with monocyte/macrophage derived cytokine and chemokine changes: results from a large international clinical trial

AIDS. 2011 Jun 1;25(9):1207-17. doi: 10.1097/QAD.0b013e3283471f10.

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).

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Cytokines / metabolism*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / physiopathology
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Interleukin-6 / metabolism
  • Lymphocyte Activation / immunology*
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophage Inflammatory Proteins / metabolism
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Virus Replication / immunology
  • Virus Replication / physiology*

Substances

  • Cytokines
  • Interleukin-6
  • Macrophage Inflammatory Proteins
  • Macrophage Colony-Stimulating Factor