title: Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).
abstract: OBJECTIVE
  Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.
  
  
  METHODS
  Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279).
  
  
  RESULTS
  Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels.
  
  
  CONCLUSIONS
  Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00084019.
authors.affiliation: Henry Ford Hospital System, Detroit, Michigan, United States of America.
authors.forename: John E
authors.initials: JE
authors.lastname: McKinnon
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Robbie B
authors.initials: RB
authors.lastname: Mailliard
authors.affiliation: University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Swindells
authors.affiliation: Weill-Cornell Medical College, New York, New York, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilkin
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Luann
authors.initials: L
authors.lastname: Borowski
authors.affiliation: George Washington University, Washington, DC, United States of America.
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Roper
authors.affiliation: Social & Scientific Systems, Inc., Silver Spring, Maryland, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bastow
authors.affiliation: HIV Drug Resistance Program, NCI, Frederick, Maryland, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Kearney
authors.affiliation: HIV Drug Resistance Program, NCI, Frederick, Maryland, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Wiegand
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
mesh_terms: D000069446:Atazanavir Sulfate; D016516:CD4-CD8 Ratio; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D000069446:Atazanavir Sulfate; D019438:Ritonavir