Maraviroc, as a switch option, in HIV-1-infected individuals with stable, well-controlled HIV replication and R5-tropic virus on their first Nucleoside/Nucleotide reverse transcriptase inhibitor plus ritonavir-boosted protease inhibitor regimen: Week 48 Results of the randomized, multicenter March study

Sarah Lilian Pett*, Janaki Amin, Andrejz Horban, Jaime Andrade-Villanueva, Marcelo Losso, Norma Porteiro, Juan Sierra Madero, Waldo Belloso, Elise Tu, David Silk, Anthony Kelleher, Richard Harrigan, Andrew Clark, Wataru Sugiura, Marcelo Wolff, John Gill, Jose Gatell, Martin Fisher, Amanda Clarke, Kiat RuxrungthamThierry Prazuck, Rolf Kaiser, Ian Woolley, Juan Alberto Arnaiz, David Cooper, Jürgen K. Rockstroh, Patrick Mallon, Sean Emery

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Background. Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)-infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus. Methods. The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1-infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < -12% in the intention-to-treat (ITT) population. Results. The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, -9.0% to 2.2%] and 91.7% [95% CI, -9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, -19.8% to -5.8%] and 77.7% [95% CI, -24.9% to -8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis. Conclusions. These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r. Clinical Trials Registration. NCT01384682.

Original languageEnglish
Pages (from-to)122-132
Number of pages11
JournalClinical Infectious Diseases
Volume63
Issue number1
DOIs
Publication statusPublished - 1 Jul 2016
Externally publishedYes

Keywords

  • maraviroc
  • switch
  • antiretroviral
  • comorbidity

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