Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial

PLoS One. 2013 Nov 14;8(11):e80157. doi: 10.1371/journal.pone.0080157. eCollection 2013.

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-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48.

Results: By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/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.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cyclohexanes / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Immunocompromised Host*
  • Interleukin-7 / blood
  • Ki-67 Antigen / blood
  • Male
  • Maraviroc
  • Middle Aged
  • RNA, Viral / antagonists & inhibitors*
  • RNA, Viral / blood
  • Treatment Outcome
  • Triazoles / therapeutic use*
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Cyclohexanes
  • IL7 protein, human
  • Interleukin-7
  • Ki-67 Antigen
  • RNA, Viral
  • Triazoles
  • Maraviroc

Associated data

  • ClinicalTrials.gov/NCT00884858

Grants and funding

This work has been funded by Pfizer, Inc., New York, NY, USA through an Investigator Initiated Research grant (to S.R.) and by Anlaids Lombardy Onlus, Milan, Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.