Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial

JAMA. 2015 Mar;313(12):1223-31. doi: 10.1001/jama.2015.1328.

Abstract

Importance: Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV infection have significant toxicities, limiting treatment uptake.

Objective: To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection, including patients with cirrhosis.

Design, setting, and participants: TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen.

Interventions: Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized.

Main outcomes and measures: The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12).

Results: Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment.

Conclusions and relevance: In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection.

Trial registration: clinicaltrials.gov Identifier: NCT01939197.

Publication types

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

MeSH terms

  • 2-Naphthylamine
  • Adult
  • Anilides / administration & dosage*
  • Anilides / adverse effects
  • Antiviral Agents / administration & dosage*
  • Carbamates / administration & dosage*
  • Carbamates / adverse effects
  • Coinfection
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV-1
  • Hepacivirus / genetics
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Humans
  • Lactams, Macrocyclic
  • Macrocyclic Compounds / administration & dosage*
  • Macrocyclic Compounds / adverse effects
  • Male
  • Middle Aged
  • Pilot Projects
  • Proline / analogs & derivatives
  • Ribavirin / administration & dosage*
  • Ribavirin / adverse effects
  • Ritonavir / administration & dosage*
  • Ritonavir / adverse effects
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Treatment Outcome
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Valine

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Sulfonamides
  • ombitasvir
  • Ribavirin
  • Uracil
  • Proline
  • 2-Naphthylamine
  • dasabuvir
  • Valine
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT01939197