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


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.
Servicio de Medicina Interna, Unidad de VIH, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.
Maria Luisa
ML
Montes
Chelsea and Westminster Hospital, London, UK.
Mark
M
Nelson
Hôpital St Antoine and INSERM, UMR S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Pierre-Marie
PM
Girard
Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Joe
J
Sasadeusz
Warsaw Medical University and Hospital of Infectious Diseases, Warsaw, Poland.
Andrzej
A
Horban
STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clínica Evandro Chagas, Rio de Janeiro, Brazil.
Beatriz
B
Grinsztejn
Saint-Petersburg AIDS Center, St Petersburg, Russian Federation.
Natalia
N
Zakharova
Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía/IMIBIC, Córdoba, Spain.
Antonio
A
Rivero
Infectious Diseases Department, L'Archet Hospital, University of Nice, Nice, France.
Jacques
J
Durant
Unidad de Enfermedades Infecciosas, Hospital General Universitario, Valencia, Spain.
Enrique
E
Ortega-Gonzalez
Janssen Infectious Diseases BVBA, Beerse, Belgium.
Erkki
E
Lathouwers
Janssen Infectious Diseases BVBA, Beerse, Belgium.
Katrien
K
Janssen
Janssen Infectious Diseases BVBA, Beerse, Belgium.
Sivi
S
Ouwerkerk-Mahadevan
Janssen Research & Development LLC, Titusville, NJ, USA jwitek@its.jnj.com.
James
J
Witek
Servicio de Medicina Interna, Unidad de VIH, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.
Juan
J
González-García
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D060085:Coinfection / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D055815:Young Adult
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a