Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial

PLoS One. 2017 Nov 21;12(11):e0187393. doi: 10.1371/journal.pone.0187393. eCollection 2017.

Abstract

Objectives: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48.

Methods: Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).

Results: In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm.

Conclusion: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / standards
  • Cyclohexanes / administration & dosage*
  • Cyclohexanes / adverse effects
  • Darunavir / administration & dosage*
  • Darunavir / adverse effects
  • Drug Therapy, Combination / adverse effects
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • Ritonavir / administration & dosage
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • Triazoles
  • Maraviroc
  • Ritonavir
  • Darunavir

Grants and funding

This work was partially funded by grants from Ministero della Salute, ISS, for Programma Nazionale AIDS project number 40H94. Janssen Europe provided Darunavir tablets for patients in the study arm and supported the pharmacovigilance of the study and ViiV Healthcare Italy supported tropism testing for all patients for conducting the study. ViiV Healthcare Italy also supported plasma antiretroviral drug monitoring for patients in the study arm for conducting the study. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.