Telaprevir in HIV-HCV Coinfected Patients Who Had Previously Failed a Peginterferon-Ribavirin Regimen (TelapreVIH)

Inclusion Criteria:

• Informed consent form signed at screening visit at the latest
• Patient registered with or covered by a social security scheme
• HIV-1 infection
• Chronic, genotype 1, hepatitis C with detectable HCV RNA at screening
• Virological failure following a previous treatment of at least 12 weeks by peginterferon alpha-2a ≥ 135 µg once weekly or peginterferon alpha-2b ≥ 1.0 µg per kg once weekly + ribavirin ≥ 600 mg once daily. Virological failure defined by persistence of a detectable HCV-RNA, with the same genotype than before. Null responder patient, with less than 2 Log10 HCV-RNA decline at week 12 with cirrhosis are excluded from the study. Null responder patients without cirrhosis (equal or below METAVIR F3) are limited to less than 30 % of all patients included
• No Interferon and/or Ribavirin within past 6 months
• Stable antiretroviral treatment for over 3 months at screening. Authorized combinations: tenofovir-emtricitabine-boosted atazanavir,tenofovir-emtricitabine-efavirenz,tenofovir-emtricitabine-raltegravir, once Drug-Drug interaction data will be available. Patients with a stable combination of at least 3 of the following drugs: tenofovir, emtricitabine/lamivudine, efavirenz, atazanavir-boosted or not, raltegravir. These patients cannot participate in the pharmacokinetic study
• CD4 >200/mm3 and >15% at screening
• Plasma HIV-RNA <50 copies/mL for at least 6 months at screening visit
• Body weight ≥ 40 kg to equal or below 125 kg
• Fibrosis stage have to be documented by a significant liver biopsy (cumulative length ≥ 15 mm or ≥ 6 portal spaces), within 3 years. Patients with a previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4) are allowed to enter the study without a new biopsy. The proportion of patients with cirrhosis lesions (METAVIR F4) is limited to 50% of all patients.
• Male patients, female patients with child-bearing potency and their heterosexual partners must use an adequate contraception from 1 month before initiation of treatment to 7 months following the end of treatment for men and to 4 months following the end of treatment for women. Subjects (or their female partners) must not be pregnant or planning to become pregnant within 2 years after enrolling in the study

Exclusion Criteria:

• Patient with liver failure (Child B and C) or past history of decompensated cirrhosis
• Significant oesophageal varices (Stages 2-3) on a gastrointestinal endoscopy within 3 years
• Detectable AgHBs
• HIV-2 co-infection
• Contra-indication to ribavirin or peginterferon
• Severe pre-existing cardiac or pulmonary disease
• Untreated dysthyroidism
• Uncontrolled Type 2 diabetes
• Optic neuritis past history and retinal condition
• History of organ transplant
• Severe hemoglobinopathy
• Congenital QT prolongation, family history of congenital QT prolongation or sudden unexpected death
• Contra-indication to telaprevir, hypersensitivity to any component of the drug product
• Any disease requiring long term, systemic corticotherapy or immunosuppressive therapy during study
• Alcohol intake that may represent an obstacle for the participation of the subject
• Substance abuse that may represent an obstacle for the participation of the subject
• Acute CDC stage C opportunistic infection within the previous 6 months
• Past history of cancer within the previous 5 years (except skin basal cell carcinoma, Kaposi's disease in stable remission, in situ cervical cancer and in situ anal cancer)
• Any active malignant disease including hepatocellular carcinoma
• Patients unable to observe the study procedures
• Participation to another clinical trial within the previous 30 days
• Haemoglobin <120 g/L for women and <130 g/L for men
• Platelets <90 000/mm3
• Neutrophils <1 500/mm3
• Renal insufficiency defined by an estimated Glomerular Filtration Rate < 60 mL/mn (MDRD equation)
• Associated medication susceptible to interfere with the pharmacokinetic parameters of telaprevir and/or antiretroviral associated drugs