Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response

An Italian randomized clinical trial

Stefano Rusconi, Paola Vitiello, Fulvio Adorni, Elisa Colella, Emanuele Focà, Amedeo Capetti, Paola Meraviglia, Clara Abeli, Stefano Bonora, Marco D'Annunzio, Antonio Di Biagio, Massimo Di Pietro, Luca Butini, Giancarlo Orofino, Manuela Colafigli, Gabriella D'Ettorre, Daniela Francisci, Giustino Parruti, Alessandro Soria, Anna Rita Buonomini & 9 others Chiara Tommasi, Silvia Mosti, Francesca Bai, Silvia Di Nardo Stuppino, Manuela Morosi, Marco Montano, Pamela Tau, Esther Merlini, Giulia Marchetti

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. Methods: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+≤200/μL and/or CD4+ recovery ≤25% and HIV-RNA200/μL and CD4>200/μL + CD4 gain ≥25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=. 01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. Conclusions: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations. Trial Registration: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858

Original languageEnglish
Article numbere80157
JournalPLoS One
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 14 2013

Fingerprint

randomized clinical trials
Highly Active Antiretroviral Therapy
Human immunodeficiency virus 1
HIV-1
T-cells
Randomized Controlled Trials
immune response
T-lymphocytes
HIV
interleukin-7
T-Lymphocytes
Interleukin-7
Viremia
viremia
HLA-DR Antigens
disease course
Disease Progression
Labels
homeostasis
Homeostasis

ASJC Scopus subject areas

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

Cite this

Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response : An Italian randomized clinical trial. / Rusconi, Stefano; Vitiello, Paola; Adorni, Fulvio; Colella, Elisa; Focà, Emanuele; Capetti, Amedeo; Meraviglia, Paola; Abeli, Clara; Bonora, Stefano; D'Annunzio, Marco; Di Biagio, Antonio; Di Pietro, Massimo; Butini, Luca; Orofino, Giancarlo; Colafigli, Manuela; D'Ettorre, Gabriella; Francisci, Daniela; Parruti, Giustino; Soria, Alessandro; Buonomini, Anna Rita; Tommasi, Chiara; Mosti, Silvia; Bai, Francesca; Stuppino, Silvia Di Nardo; Morosi, Manuela; Montano, Marco; Tau, Pamela; Merlini, Esther; Marchetti, Giulia.

In: PLoS One, Vol. 8, No. 11, e80157, 14.11.2013.

Research output: Contribution to journalArticle

Rusconi, S, Vitiello, P, Adorni, F, Colella, E, Focà, E, Capetti, A, Meraviglia, P, Abeli, C, Bonora, S, D'Annunzio, M, Di Biagio, A, Di Pietro, M, Butini, L, Orofino, G, Colafigli, M, D'Ettorre, G, Francisci, D, Parruti, G, Soria, A, Buonomini, AR, Tommasi, C, Mosti, S, Bai, F, Stuppino, SDN, Morosi, M, Montano, M, Tau, P, Merlini, E & Marchetti, G 2013, 'Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: An Italian randomized clinical trial', PLoS One, vol. 8, no. 11, e80157. https://doi.org/10.1371/journal.pone.0080157
Rusconi, Stefano ; Vitiello, Paola ; Adorni, Fulvio ; Colella, Elisa ; Focà, Emanuele ; Capetti, Amedeo ; Meraviglia, Paola ; Abeli, Clara ; Bonora, Stefano ; D'Annunzio, Marco ; Di Biagio, Antonio ; Di Pietro, Massimo ; Butini, Luca ; Orofino, Giancarlo ; Colafigli, Manuela ; D'Ettorre, Gabriella ; Francisci, Daniela ; Parruti, Giustino ; Soria, Alessandro ; Buonomini, Anna Rita ; Tommasi, Chiara ; Mosti, Silvia ; Bai, Francesca ; Stuppino, Silvia Di Nardo ; Morosi, Manuela ; Montano, Marco ; Tau, Pamela ; Merlini, Esther ; Marchetti, Giulia. / Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response : An Italian randomized clinical trial. In: PLoS One. 2013 ; Vol. 8, No. 11.
@article{a8a7b137b1ba4ef2aa14d46f46db0852,
title = "Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: An Italian randomized clinical trial",
abstract = "Background: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. Methods: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+≤200/μL and/or CD4+ recovery ≤25{\%} and HIV-RNA200/μL and CD4>200/μL + CD4 gain ≥25{\%} end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=. 01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. Conclusions: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations. Trial Registration: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858",
author = "Stefano Rusconi and Paola Vitiello and Fulvio Adorni and Elisa Colella and Emanuele Foc{\`a} and Amedeo Capetti and Paola Meraviglia and Clara Abeli and Stefano Bonora and Marco D'Annunzio and {Di Biagio}, Antonio and {Di Pietro}, Massimo and Luca Butini and Giancarlo Orofino and Manuela Colafigli and Gabriella D'Ettorre and Daniela Francisci and Giustino Parruti and Alessandro Soria and Buonomini, {Anna Rita} and Chiara Tommasi and Silvia Mosti and Francesca Bai and Stuppino, {Silvia Di Nardo} and Manuela Morosi and Marco Montano and Pamela Tau and Esther Merlini and Giulia Marchetti",
year = "2013",
month = "11",
day = "14",
doi = "10.1371/journal.pone.0080157",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response

T2 - An Italian randomized clinical trial

AU - Rusconi, Stefano

AU - Vitiello, Paola

AU - Adorni, Fulvio

AU - Colella, Elisa

AU - Focà, Emanuele

AU - Capetti, Amedeo

AU - Meraviglia, Paola

AU - Abeli, Clara

AU - Bonora, Stefano

AU - D'Annunzio, Marco

AU - Di Biagio, Antonio

AU - Di Pietro, Massimo

AU - Butini, Luca

AU - Orofino, Giancarlo

AU - Colafigli, Manuela

AU - D'Ettorre, Gabriella

AU - Francisci, Daniela

AU - Parruti, Giustino

AU - Soria, Alessandro

AU - Buonomini, Anna Rita

AU - Tommasi, Chiara

AU - Mosti, Silvia

AU - Bai, Francesca

AU - Stuppino, Silvia Di Nardo

AU - Morosi, Manuela

AU - Montano, Marco

AU - Tau, Pamela

AU - Merlini, Esther

AU - Marchetti, Giulia

PY - 2013/11/14

Y1 - 2013/11/14

N2 - Background: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. Methods: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+≤200/μL and/or CD4+ recovery ≤25% and HIV-RNA200/μL and CD4>200/μL + CD4 gain ≥25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=. 01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. Conclusions: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations. Trial Registration: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858

AB - Background: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. Methods: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+≤200/μL and/or CD4+ recovery ≤25% and HIV-RNA200/μL and CD4>200/μL + CD4 gain ≥25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=. 01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. Conclusions: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations. Trial Registration: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858

UR - http://www.scopus.com/inward/record.url?scp=84893589615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893589615&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0080157

DO - 10.1371/journal.pone.0080157

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e80157

ER -