Pilot Study to Assess the Efficacy of and Tolerance to a QUadruple Therapy to Treat HIV-HCV Coinfected Patients Previously Null Responders (QUADRIH)

This is an interventional diagnostic trial for HCV-HIV Co-Infection focused on measuring HCV-HIV Co-Infection, Quadruple therapy, null responder to a standard Pegylated interferon/Ribavirin regimen Read More

Inclusion Criteria:

• Adult ≥18 years with confirmed HIV-1 or 2 infection
• Infection with HCV genotype 1 or 4 only, confirmed and with detectable HCV-RNA ≥ 1000 IU/mL at screening.
• Null responders to a previous treatment with Peginterferon and Ribavirin, defined by a fall of less than 2 log10 IU/ml HCV-RNA from baseline to week 12.
• Stable antiretroviral treatment for > 1 month at screening containing any of the following drugs: Raltegravir, Enfuvirtide, Tenofovir-Emtricitabine, Abacavir-Lamivudine.
• CD4 > 200 /mm3 and > 15% at screening
• HIV-RNA < 400 copies/mL from ≥ 3 months at screening
• Any liver fibrosis stage,

• with the assessment of the presence or not of cirrhosis at screening:

  • previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4), and/or
  • significant liver biopsy (cumulative length ≥ 15 mm and ≥ 6 portal spaces), within 18 months and after the end of last HCV treatment, and/or
  • significant and reliable liver stiffness assessment (Fibroscan®) within 6 months (at least 10 measures with IQR less then 25% of the mean value and a success rate of at least 80%)
• cirrhosis being defined as a METAVIR score F4 on liver biopsy and/or liver elastometry ≥ 15 kPa
• the proportion of patients with cirrhosis (METAVIR F4) is limited to 50% of all patients.
• Body weight ≥ 40 kg and ≤125 kg
• Male patients, female patients with child-bearing potential and their heterosexual partners must use 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.
• Informed and signed consent
• For participating patients, informed and signed consent for the pharmacokinetic sub-study
• Patients affiliated to the National Health Insurance or covered by Universal Medical Coverage
• For the first 12 patients included (who will participate to the pharmacological substudy): stable antiretroviral treatment for > 1 month at screening, with Raltegravir+ Emtricitabine+ Tenofovir

Exclusion Criteria:

• CHILD B and C cirrhosis, past history of decompensated cirrhosis. Patients with CHILD A cirrhosis must demonstrate the absence of significant oesophageal varices (Stages 2-3) on an upper gastrointestinal endoscopy ≤ 12 months
• Positive HBs antigenemia with HBV DNA > 1000 IU/ml((if positive AgHBs with HBV DNA ≤ 1000 IU/mL, patient will be included provided it is treated with Ténofovir)
• Pregnant women, breast-feeding women
• Refusal of adequate contraception
• Contra-indication to Ribavirin, including hypersensitivity reaction to Ribavirin
• Contra-indication to Peginterferon, including psychiatric contra-indications. Patients with significant psychiatric past history, notably severe depression requiring hospitalization or suicide attempt, cannot be included unless they undergo a psychiatric evaluation and obtain a specific authorization for the use of interferon.
• Premature discontinuation (during the first six months) of a previous HCV treatment for toxicity. Patients who have stopped a previous treatment for severe anaemia or neutropenia can enter the study if erythropoietin or granulocyte growth factor had not been used during the previous treatment
• Previous HCV therapy including HCV NS3 protease inhibitor
• Severe pre-existing cardiac or pulmonary disease
• History of organ transplant
• Acute CDC stage C opportunistic infection occurring within the previouW6 months
• Any active malignant disease including hepatocellular carcinoma for which a specific assessment is required at screening
• Alcohol intake that may represent an obstacle for the participation of the subject in the study
• Substance abuse that may represent an obstacle for the participation of the subject in the study. Stabilized patients included in a substitution program can participate in the study
• Patients with previous observance problem unable to observe the study procedures
• Participation in another clinical trial within the previous 30 days
• Haemoglobin < 90 g/L
• Platelets < 50 000 /mm3
• Neutrophil count < 750 /mm3
• Renal insufficiency defined by an estimated Glomerular Filtration Rate < 50 mL/mn (MDRD equation)
• Absence of antiretroviral treatment or antiretroviral treatment different from the authorized combinations
• Associated medication likely to interfere with any of the study drugs such as CPY3A4 inducers (rifampin, Millepertuis)