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.

Sustained exacerbation of cryoglobulinaemia-related vasculitis following treatment of hepatitis C with peginterferon alfa.

Peginterferon is now the gold standard of therapy in patients with chronic hepatitis C virus infection. Extrahepatic manifestations of HCV are usually treated with interferon alfa. Here we report on a patient with HCV-related cirrhosis and cryoglobulinaemia who presented with an acute and long-lasting exacerbation of vasculitis during treatment with peginterferon. To our knowledge this is the first report of an acute exacerbation of cryoglobulinaemia-related vasculitis involving skin, peripheral nerve and kidney in a patient treated with peginterferon for HCV-related cirrhosis. The long half-life of peginterferon might explain the long-lasting symptoms of vasculitis. Clinicians should be aware of possible sustained flare of cryoglobulinaemia-associated vasculitis in patients receiving peginterferon.