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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere95524
JournalPloS one
Volume9
Issue number5
DOIs
StatePublished - May 6 2014

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Ritonavir
Natural Killer T-Cells
T-cells
natural killer cells
Lymphocytes
T-lymphocytes
nucleosides
Chemical activation
Human immunodeficiency virus 1
T-Lymphocytes
Nucleosides
Natural Killer Cells
HIV-1
lymphocytes
Population
Recovery
therapeutics
HLA-DR Antigens
Survival Analysis
Lymphocyte Activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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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, John E.; Mailliard, Robbie B.; Swindells, Susan; Wilkin, Timothy J.; Borowski, LuAnn; Roper, Jillian M.; Bastow, Barbara; Kearney, Mary; Wiegand, Ann; Mellors, John W.; Rinaldo, Charles R.

In: PloS one, Vol. 9, No. 5, e95524, 06.05.2014.

Research output: Contribution to journalArticle

McKinnon, JE, Mailliard, RB, Swindells, S, Wilkin, TJ, Borowski, L, Roper, JM, Bastow, B, Kearney, M, Wiegand, A, Mellors, JW & 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, vol. 9, no. 5, e95524. https://doi.org/10.1371/journal.pone.0095524
McKinnon, John E. ; Mailliard, Robbie B. ; Swindells, Susan ; Wilkin, Timothy J. ; Borowski, LuAnn ; Roper, Jillian M. ; Bastow, Barbara ; Kearney, Mary ; Wiegand, Ann ; Mellors, John W. ; Rinaldo, Charles R. / Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201). In: PloS one. 2014 ; Vol. 9, No. 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 na{\"i}ve 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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T1 - Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

AU - McKinnon, John E.

AU - Mailliard, Robbie B.

AU - Swindells, Susan

AU - Wilkin, Timothy J.

AU - Borowski, LuAnn

AU - Roper, Jillian M.

AU - Bastow, Barbara

AU - Kearney, Mary

AU - Wiegand, Ann

AU - Mellors, John W.

AU - Rinaldo, Charles R.

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N2 - 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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