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

McKinnon, JE and Mailliard, RB and Swindells, S and Wilkin, TJ and Borowski, LA and Roper, JM and Bastow, B and Kearney, M and Wiegand, A and Mellors, JW and Rinaldo, CR (2014) Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201). PLoS ONE, 9 (5).

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Abstract

Objectives: 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. Trial Registration: ClinicalTrials.gov NCT00084019.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
McKinnon, JE
Mailliard, RBrbm19@pitt.eduRBM190000-0001-5501-503X
Swindells, S
Wilkin, TJ
Borowski, LA
Roper, JM
Bastow, B
Kearney, M
Wiegand, A
Mellors, JWjwm1@pitt.eduJWM1
Rinaldo, CRRINALDO@pitt.eduRINALDO
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorKumar, AnilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 6 May 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0095524
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
School of Medicine > Medicine
School of Medicine > Pathology
Refereed: Yes
Date Deposited: 30 Jun 2014 15:15
Last Modified: 02 Feb 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/22005

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