title: Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.
abstract: BACKGROUND
  The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood.
  
  
  METHODS
  Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy.
  
  
  RESULTS
  Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy.
  
  
  CONCLUSIONS
  ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00660972.
authors.affiliation: Case Western Reserve University, Division of Infectious Diseases and HIV Medicine, Cleveland, Ohio, United States of America.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.affiliation: The Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Adriana
authors.initials: A
authors.lastname: Andrade
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenkranz
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Darlene
authors.initials: D
authors.lastname: Lu
authors.affiliation: Case Western Reserve University, Division of Infectious Diseases and HIV Medicine, Cleveland, Ohio, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Clagett
authors.affiliation: Case Western Reserve University, Division of Infectious Diseases and HIV Medicine, Cleveland, Ohio, United States of America.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Pilch-Cooper
authors.affiliation: Case Western Reserve University, Division of Infectious Diseases and HIV Medicine, Cleveland, Ohio, United States of America.
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: University of Cincinnati Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Judith
authors.initials: J
authors.lastname: Feinberg
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, California, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Daar
authors.affiliation: University of Pittsburg Medical Center, Pittsburg, Pennsylvania, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Mellors
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kuritzkes
authors.affiliation: Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.affiliation: Case Western Reserve University, Division of Infectious Diseases and HIV Medicine, Cleveland, Ohio, United States of America.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D063065:Organophosphonates; D011760:Pyrrolidinones; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine