A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses

Antivir Ther. 2012;17(7):1301-9. doi: 10.3851/IMP2350. Epub 2012 Sep 5.


Background: Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities.

Methods: We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral loads and poor CD4(+) T-cell responses on long-term stable HAART to assess whether the addition of raltegravir would have an effect on biomarkers of chronic inflammation. A total of 26 patients were followed for 1 year on the intensified regimen. In addition to T-cell responses, we evaluated changes in activated CD4(+) and CD8(+) T-cells, several pro-inflammatory cytokines and chemokines and memory cell responses to HIV-1-associated peptides.

Results: Although there was no improvement in CD4(+) T-cell counts, the percentage change in CD4(+)%, CD4(+)/CD8(+) ratios and RANTES (regulated on activation normal T-cells expressed and secreted) increased significantly while the percentage change in CD8(+) T-cell counts and CD8(+)%, activated CD4(+) T-cells and several pro-inflammatory chemokines and cytokines decreased significantly. The percentage change in HIV-1-specific nef, pol set 1, gag and env memory T-cells also declined.

Conclusions: The addition of raltegravir to a virologically suppressive HAART regimen in patients with poor immunological responses resulted in the reduction of several pro-inflammatory biomarkers; increases were seen in RANTES levels and CD4(+)/CD8(+) T-cell ratios. The clinical relevance of these observations is beyond the scope of this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active / methods
  • Biomarkers / metabolism
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Chemokine CCL5 / metabolism
  • Disease Progression
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / pathogenicity
  • Humans
  • Immunologic Memory
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / virology
  • Inflammation Mediators / immunology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Pilot Projects
  • Pyrrolidinones / pharmacology*
  • Raltegravir Potassium
  • Viral Load
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / metabolism
  • nef Gene Products, Human Immunodeficiency Virus / immunology
  • nef Gene Products, Human Immunodeficiency Virus / metabolism


  • Biomarkers
  • CCL5 protein, human
  • Chemokine CCL5
  • Inflammation Mediators
  • Pyrrolidinones
  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • Raltegravir Potassium