Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

John E McKinnon; Robbie B Mailliard; Susan Swindells; Timothy J Wilkin; Luann Borowski; Jillian M Roper; Barbara Bastow; Mary Kearney; Ann Wiegand; John W Mellors; Charles R Rinaldo; A5201 study team

doi:10.1371/journal.pone.0095524

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Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

Journal article

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Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

John E McKinnon, Robbie B Mailliard, Susan Swindells, Timothy J Wilkin, Luann Borowski, Jillian M Roper, Barbara Bastow, Mary Kearney, Ann Wiegand, John W Mellors, …

PloS one, Vol.9(5), pp.e95524-e95524

2014

DOI: 10.1371/journal.pone.0095524

PMCID: PMC4011688

PMID: 24802242

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Abstract

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. 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). 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. 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. ClinicalTrials.gov NCT00084019.

HIV-1 - drug effects

Humans

RNA, Viral - blood

HIV Protease Inhibitors - therapeutic use

Oligopeptides - therapeutic use

HIV Protease Inhibitors - pharmacology

HIV Infections - immunology

CD4-CD8 Ratio

HIV-1 - immunology

Atazanavir Sulfate

Killer Cells, Natural - immunology

Ritonavir - therapeutic use

HIV Infections - drug therapy

Ritonavir - pharmacology

Killer Cells, Natural - drug effects

Pyridines - pharmacology

Oligopeptides - pharmacology

Pyridines - therapeutic use

Details

Title: Subtitle: Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)
Creators: John E McKinnon - Henry Ford Hospital System, Detroit, Michigan, United States of America
Robbie B Mailliard - University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Susan Swindells - University of Nebraska Medical Center, Omaha, Nebraska, United States of America
Timothy J Wilkin - Weill-Cornell Medical College, New York, New York, United States of America
Luann Borowski - University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Jillian M Roper - George Washington University, Washington, DC, United States of America
Barbara Bastow - Social & Scientific Systems, Inc., Silver Spring, Maryland, United States of America
Mary Kearney - HIV Drug Resistance Program, NCI, Frederick, Maryland, United States of America
Ann Wiegand - HIV Drug Resistance Program, NCI, Frederick, Maryland, United States of America
John W Mellors - University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Charles R Rinaldo - University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
A5201 study team
Contributors: Jeffery Meier (Contributor) - University of Iowa, Internal Medicine
Resource Type: Journal article
Publication Details: PloS one, Vol.9(5), pp.e95524-e95524
DOI: 10.1371/journal.pone.0095524
PMID: 24802242
PMCID: PMC4011688
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: KL2 RR024154 / NCRR NIH HHS U01 AI035041 / NIAID NIH HHS UM1 AI106701 / NIAID NIH HHS K12 RR024154 / NCRR NIH HHS UM1 AI069415 / NIAID NIH HHS UM1 AI069494 / NIAID NIH HHS UM1 AI069423 / NIAID NIH HHS AI069450 / NIAID NIH HHS U01 AI068636 / NIAID NIH HHS U01-AI068636 / NIAID NIH HHS U01 AI069423 / NIAID NIH HHS UM1 AI068636 / NIAID NIH HHS U01 AI069450 / NIAID NIH HHS 1R21-AI084423-02 / NIAID NIH HHS UL1 RR024153 / NCRR NIH HHS R37-AI41870 / NIAID NIH HHS UM1 AI069450 / NIAID NIH HHS R21 AI084423 / NIAID NIH HHS 1KL2- RR024154-03 / NCRR NIH HHS UM1 AI068634 / NIAID NIH HHS UM1 AI069419 / NIAID NIH HHS U01-AI35041 / NIAID NIH HHS R37 AI041870 / NIAID NIH HHS
Language: English
Date published: 2014
Academic Unit: Infectious Diseases; Epidemiology; Internal Medicine
Record Identifier: 9984094542002771

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