title: 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.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, National Jewish Health, Denver, CO, USA. lichtensteink@njhealth.org
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Lichtenstein
authors.forename: Carl
authors.initials: C
authors.lastname: Armon
authors.forename: Vijaya
authors.initials: V
authors.lastname: Nagabhushanam
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Efaw
authors.forename: Ashley
authors.initials: A
authors.lastname: Frazer-Abel
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Hiserote
authors.forename: Rafeul
authors.initials: R
authors.lastname: Alam
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000378:metabolism; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018946:Chemokine CCL5 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018836:Inflammation Mediators / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D018836:Inflammation Mediators; D011760:Pyrrolidinones; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D000068898:Raltegravir Potassium