Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial

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• 作者：Mark Sulkowski ; Stanislas Pol ; Josep Mallolas ; Hugo Fainboim ; Curtis Cooper ; Jihad Slim ; Antonio Rivero ; Carmen Mak ; Seth Thompson ; Anita YM Howe ; Larissa Wenning ; Peter Sklar ; Janice Wahl ; Wayne Greaves ; for the P05411 study investigators
• 刊名：The Lancet Infectious Diseases
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：13
• 期：7
• 页码：597-605
• 全文大小：333 K

文摘

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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 ¦Ìg/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 , number .

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.

Funding

Merck.