Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial)

J Antimicrob Chemother. 2015 Dec;70(12):3339-44. doi: 10.1093/jac/dkv280. Epub 2015 Sep 22.

Abstract

Objectives: ROCnRAL ANRS-157 was a single-arm study designed to evaluate a switch to a maraviroc (300 mg twice a day) plus raltegravir (400 mg twice a day) regimen in virologically suppressed HIV-1-infected patients (ClinicalTrials.gov: NCT01420523). The aim of this work was to investigate the factors associated with virological failure (VF) (5/44 patients) or virological rebound defined as one viral load (VL) >50 copies/mL or VL >1 copy/mL.

Methods: At baseline (BL), ultradeep sequencing (UDS) of DNA gp120 V3 and integrase regions and quantification of HIV DNA were performed in PBMCs. Tropism, VL, BL ultrasensitive HIV RNA VL, BL HIV DNA VL, subtype, age, ethnicity, transmission group, AIDS status, nadir CD4 and BL CD4 cell count, time since HIV diagnosis, duration of ART and suppressed viraemia, VL zenith, CD4/CD8 ratio and BL CD8 cell count were investigated as potential factors associated with virological rebound.

Results: The proportion of patients with VL <1 copy/mL did not evolve over time. Among the 44 included patients, 3 had minority X4-tropic viruses determined by UDS at BL and one of them presented VF. Minority resistant variants in the integrase gene were detected at BL at two positions (E138 and G140) for three patients who did not have VF. Among all studied factors, none was associated with virological rebound.

Conclusions: Maraviroc plus raltegravir failed to maintain virological suppression in virologically suppressed HIV-1-infected patients. However, neither minority viral variants nor ultrasensitive viraemia was found to be a predictive factor of VF or virological rebound in this context.

Publication types

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

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Cyclohexanes / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / isolation & purification*
  • Maraviroc
  • Raltegravir Potassium / therapeutic use*
  • Risk Factors
  • Treatment Failure
  • Triazoles / therapeutic use*
  • Viral Load

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • Triazoles
  • Raltegravir Potassium
  • Maraviroc

Associated data

  • ClinicalTrials.gov/NCT01420523