Patterns of viral load decline with telaprevir-based therapy in patients with genotype 1 chronic HCV infection

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• 作者：Gaston Picchio ; S ; ra De Meyer ; Inge Dierynck ; Anne Ghys ; Linda Gritz ; Tara L. Kieffer ; Douglas J. Bartels ; Jim Witek ; Leif Bengtsson ; Donghan Luo ; Robert S. Kauffman ; Nathalie Adda ; Christoph Sarrazin
• 关键词：Telaprevir ; Hepatitis C ; HCV RNA ; Stopping rule ; Viral load
• 刊名：Journal of Clinical Virology
• 出版年：March, 2014
• 年：2014
• 卷：59
• 期：3
• 页码：148-155
• 全文大小：2431 K

文摘

Background

Telaprevir-based therapy is associated with rapid decline in HCV RNA, enabling the application of early futility rules.

Objectives

To familiarize physicians with this paradigm, a comprehensive analysis of the most frequent HCV viral load profiles observed during treatment with telaprevir/Peg-IFN/RBV in Phase III trials is provided.

Design

HCV RNA profiles were analyzed from 320 HCV genotype 1 treatment-na茂ve patients enrolled in the ADVANCE study, and 225 prior Peg-IFN/RBV treatment-experienced patients enrolled in the REALIZE study. Patients received 12 weeks of telaprevir with either 24 or 48 weeks of Peg-IFN alfa-2a/RBV. Patients with missing SVR assessments during follow-up, detectable HCV RNA at end of treatment but who did not have viral breakthrough (vBT), or with early vBT who discontinued telaprevir before time of failure were excluded.

Results

All analyzed patients experienced a rapid decline in HCV RNA (>2.0 log₁₀) by Day 14, irrespective of baseline characteristics and/or prior response to Peg-IFN/RBV (relapse, partial response and null response). Subsequently, HCV RNA continued to decline to undetectable levels in most patients. These patients went on to have one of the following outcomes: sustained virologic response, late vBT (after Week 12, i.e. during the Peg-IFN/RBV phase), or relapse. In the small subset of patients with early vBT or meeting a futility rule before Week 12, HCV RNA usually never became undetectable and/or increased rapidly after reaching the nadir.

Conclusions

HCV RNA profiles with telaprevir/Peg-IFN/RBV are different from those with Peg-IFN/RBV alone. It is important that clinicians understand these HCV RNA profiles and monitor patient viral load in order to apply futility rules correctly.