Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial.

BACKGROUND: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. METHODS: HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS: Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. CONCLUSIONS: Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.

Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: the HEPAIG study.

UNLABELLED: Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log(10) IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3-65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0-94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). CONCLUSION: The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV-infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of HCV genotype.