Coinfection with HCV genotype 1 and HIV
Conditions
Interventions
Product Name: SOF/LDV/FDC
Product Code: GS-7977/GS-5885 FDC
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sofosbuvir
CAS Number: 1190307-88-0
Other descriptive name: SOFOSBUVIR
Concentr
Sponsors
INSERM-ANRS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult =18 years • Confirmed HIV infection • Infection with HCV genotype 1 only, confirmed at screen visit, with a HCV-RNA = 1000 UI/mL at screen visit • Treatment-experienced subjects with: - previous virological failure to tritherapy with Peginterferon/Ribavirin and protease inhibitor, - or premature discontinuation of previous tritherapy with Peginterferon/Ribavirin and protease inhibitor due to intolerance to Peginterferon or protease inhibitor • Anti-HCV treatment stopped for at least the last 3 months • Patients on a stable (for more than 1 month) antiretroviral treatment consisting of an emtricitabine/tenofovir or lamivudine/tenofovir standard of care backbone plus efavirenz or raltegravir or rilpivirine or enfuvirtide. • CD4 > 100/mm3 and > 15% at screen visit • HIV-RNA =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Child-Pugh B or C cirrhosis or history of decompensated cirrhosis. Co-infection with Hepatitis B virus (AgHBs +) with HBV DNA > 1000 UI/ml Pregnant or breast-feeding women Transplant recipients Opportunistic infections (stage C), active or occurred within 6 months prior to baseline Evolutive malignancy, including hepatocarcinoma which should be controlled prior to baseline Alcohol or drug consumption which may affect the study participation according to the investigator. Patients included in a programme of substitution with methadone or buprenorphine could be enrolled. The opinion of a consultant in addictology is recommended for patients presenting with current drug use or drug use during the previous year. Patients with a history of non-adherence, who will be at risk of being unable to respect the study follow-up timetable Patients participating in another clinical trial within 30 days prior to inclusion Hb < 10 g/dL (female) or < 11g/dL (male) Platelets < 50 000/mm3 Neutrophil count < 750/mm3 Renal failure defined as creatinine clearance (MDRD) < 60ml/min Other antiretroviral drugs than those allowed in the study Contra-indications to Sofosbuvir, Ledipasvir, Ribavirin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy and safety of 24 weeks of a triple oral combination with Sofosbuvir/Ledipasvir fixed-dose combination and Ribavirin in subjects with HCV genotype 1 infection and HIV co-infection, who have previously failed a NS3/4A protease inhibitor plus PEG/RBV regimen or stopped prematurely their treatment for intolerance.;Secondary Objective: Safety assessment HCV virological assessment Describe HCV virological kinetics and response, globally and according to the subtype (1a or 1b) Study the prognostic factors associated with SVR Assess the emergence of resistance to Sofosbuvir and/or Ledipasvir HIV virological assessment Hepatic and metabolic evaluation: evaluate the relationship and virological response Describe Ribavirin residual concentration one month after its introduction and study its relationship with the variation of hemoglobinemia and virological response kinetics ;Primary end point(s): Sustained virological response, defined by an undetectable plasma HCV RNA 12 weeks post-treatment (SVR12);Timepoint(s) of evaluation of this end point: 12 weeks post-treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: through the study;Secondary end point(s): Safety SVR rate 24 weeks (i.e. W48) after the end of treatment globally and according to the HCV subtype (1a or 1b) Measurements of HCV RNA at D0, W1, W2, W4, W8, W12, W16, W20, W24, and 4, 8, 12, 18 and 24 weeks after the end of the treatment (W28, W32, W36, W42 and W48), globally and according to the HCV subtype (1a or 1b) HCV resistance mutations to Sofosbuvir and/or Ledipasvir (in case of virological failure) Plasma HIV RNA levels at D0, W4, W8, W12, W16, W20, W24, W36 and W48 CD4 and CD8 cell counts (absolute count, percentage and CD4/CD8 ratio) at D0, W4, W8, W12, W16, W20, W24, W36 and W48 Hepatic and metabolic assessment Biological (Fibrotest®, Fibromètre® or Hepascore ®) and imaging (Fibroscan®) parameters describing the evolution of liver fibrosis between baseline and 24 weeks post-treatment (W48) Insulin resistance measured using the HOMA-IR score (measured at D0 and W36) Parameters that define metabolic syndrome (waist circumference, blood pressure, fasting glucose, triglyceridemia, HDL-cholesterol) measured at D0 and W36 In all patients: Ribavirin residual concentration (Cres) at W4 -In all patients: Sofosbuvir and Ledipasvir residual concentrations at W4, W12 and W24 In a sub-group of 20 voluntary patients (preferred Anti Retroviral Treatment (ART) for these patients will be RAL+ TDF/FTC): PharmacoKinetic (PK) parameters (Cres, Cmax, AUC10, AUC24) of HIV drugs (Raltegravir and Tenofovir) at D0 and W4 PharmacoKinetic (PK) parameters (Cres, Cmax, AUC10, AUC24) of Sofosbuvir and Ledipasvir at W4. Patients’ reported outcomes (PRO) including perceived symptoms reported by the patients (ANRS AC24 perceived symptoms questionnaire), fatigue intensity and quality of life (MOS-SF12) at follow-up visits D0, W8, W24 and W48. PRO will be available from patients’ answers in the self-administered questionnaires. Patients’ adherence measured using the Inserm-ANRS self–a | — |
Countries
France
Contacts
Public ContactFougerou
Service de Pharmacologie Clinique – CIC Inserm 0203 - CHU de RENNES
Outcome results
None listed