The Lancet Infectious Diseases, Early Online Publication, 12 June 2013
doi:10.1016/S1473-3099(13)70149-X
Prof Mark Sulkowski MD a, Prof Stanislas Pol MD b, Josep Mallolas MD c, Hugo Fainboim MD d, Curtis Cooper MD e, Jihad Slim MD f, Antonio Rivero MD g, Carmen Mak PhD h, Seth Thompson PhD h, Anita YM Howe PhD h, Larissa Wenning PhD h, Peter Sklar MD h, Janice Wahl MD h, Dr Wayne Greaves MD h , for the P05411 study investigators†
Summary
Background
Rates of sustained virological response (SVR) to peginterferon—ribavirin are low in patients with hepatitis C virus (HCV) genotype 1 and HIV. We aimed to assess efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterferon) and ribavirin, which increases rates of SVR in patients with HCV alone.
Methods
In our double-blind, randomised controlled phase 2 trial, we enrolled adults (18—65 years) with untreated HCV genotype 1 infection and controlled HIV (HIV RNA <50 copies per mL) at 30 academic and non-academic study sites. We randomly allocated patients (1:2) according to a computer generated sequence, stratified by Metavir score and baseline HCV RNA level, to receive peginterferon 1·5 μg/kg per week with weight-based ribavirin (600—1400 mg per day) for 4 weeks, followed by peginterferon—ribavirin plus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks. Non-nucleoside reverse-transcriptase inhibitors, zidovudine, and didanosine were not permitted. The primary efficacy endpoint was SVR (defined as undetectable plasma HCV RNA) at follow-up week 24 after end of treatment. We assessed efficacy and safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00959699.
Findings
From Jan 15, 2010, to Dec 29, 2010, we enrolled 99 patients, 98 of whom received at least one treatment dose. 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compared with ten (29%) of 34 control patients (difference 33·1%, 95% CI 13·7—52·5; p=0·0008). Adverse events were more common in patients who received boceprevir than in control patients: 26 (41%) versus nine (26%) had anaemia, 23 (36%) versus seven (21%) pyrexia, 22 (34%) versus six (18%) decreased appetite, 18 (28%) versus five (15%) dysgeusia, 18 (28%) versus five (15%) vomiting, and 12 (19%) versus two (6%) neutropenia. Three patients who received boceprevir plus peginterferon—ribavirin and four controls had HIV virological breakthrough.
Interpretation
Boceprevir in combination with peginterferon—ribavirin could be an important therapeutic option for patients with HCV and HIV.
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