Telaprevir-based therapy in patients coinfected with chronic hepatitis C virus infection and HIV: INSIGHT study

J Antimicrob Chemother. 2016 Jan;71(1):244-50. doi: 10.1093/jac/dkv323. Epub 2015 Oct 19.

Abstract

Objectives: INSIGHT (ClinicalTrials.gov NCT01513941) evaluated the efficacy, safety and pharmacokinetics of telaprevir-based therapy and specific antiretroviral agents in hepatitis C virus genotype 1 (HCV-1)/HIV-1-coinfected patients.

Patients and methods: Open-label, Phase IIIb, multicentre study of telaprevir with pegylated-IFN (Peg-IFN) α2a and ribavirin in treatment-naive or -experienced HCV-1/HIV-1-coinfected patients on stable HIV HAART comprising efavirenz, atazanavir/ritonavir, darunavir/ritonavir, raltegravir, etravirine or rilpivirine with two nucleos(t)ide analogues. Patients received 750 mg telaprevir (1125 mg, if on efavirenz) every 8 h plus 180 μg/week Peg-IFNα2a and 800 mg/day ribavirin for 12 weeks, followed by Peg-IFNα2a and ribavirin alone for 12 weeks (HCV treatment naive and relapsers without cirrhosis, with extended rapid virological response) or 36 weeks (all others).

Results: Overall, 162 patients (median age of 46 years, 78% male, 92% Caucasian and mean CD4 count of 687 cells/mm(3)) were treated; 13% had cirrhosis. One-hundred-and-thirty-two patients (81%) completed telaprevir; 14 (9%) discontinued due to an adverse event (AE). Sustained virological response (SVR) 12 rates (<25 IU/mL HCV RNA 12 weeks after the last planned treatment dose) in treatment-naive patients, relapsers and non-responders were 64% (41 of 64), 62% (18 of 29) and 49% (34 of 69), respectively. SVR12 rates ranged from 51% (33 of 65) (patients receiving efavirenz) to 77% (13 of 17) (patients receiving raltegravir). Most frequently reported AEs during telaprevir treatment were pruritus (43%) and rash (34%) special search categories. Anaemia special search category occurred in 15% of patients; 6% of patients reported a serious AE.

Conclusions: In treatment-naive/-experienced HCV-1/HIV-1 patients there were significantly higher SVR rates with telaprevir-based therapy compared with pre-specified historical controls, and safety comparable to that in HCV-monoinfected patients.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Coinfection / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interferon-alpha / pharmacokinetics
  • Male
  • Middle Aged
  • Oligopeptides / administration & dosage*
  • Oligopeptides / adverse effects
  • Oligopeptides / pharmacokinetics
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / pharmacokinetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects
  • Ribavirin / pharmacokinetics
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Oligopeptides
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT01513941