Individualized treatment strategy according to early viral kinetics in hepatitis C virus type 1–infected patients

Authors


  • Presented in part at the Annual Meetings of the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases in 2006.

  • Potential conflicts of interest: Dr. Berg advises, is on the speakers' bureau of, and received grants from Roche and Schering-Plough. Dr. Klinker is a consultant for and lectures for Bristol-Myers Squibb, and GlaxoSmithKline. He also lectures for Boehringer Ingelheim, Roche, Gilead, and Tibotec. He lectures for and received grants from Essex. He is a consultant for Merck Sharp & Dohme and received grants from Abbott. Dr. Buggisch is on the speakers' bureau of Roche. Dr. Sarrazin is on the speakers' bureau of and received grants from Essex. Dr. Zeuzem is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche and Schering-Plough.

Abstract

Individualized treatment on the basis of early viral kinetics has been discussed to optimize antiviral therapy in chronic hepatitis C virus (HCV) infection. Individually tailored reduction in treatment duration in HCV type 1–infected patients represents one possible strategy. Four hundred thirty-three patients were randomly assigned to receive either 1.5 μg/kg peginterferon alfa-2b weekly plus 800-1,400 mg ribavirin daily for 48 weeks (n = 225, group A) or an individually tailored treatment duration (18-48 weeks; n = 208, group B). In the latter group, treatment duration was calculated using the time required to induce HCV RNA negativity (branched DNA [bDNA] assay; sensitivity limit, 615 IU/mL) multiplied by the factor 6. All bDNA negative samples were retested with the more sensitive transcription-mediated amplification (TMA) assay (sensitivity limit, 5.3 IU/mL). Sustained virologic response (SVR) rates were significantly lower in group B (34.6% versus 48.0% [P = 0.005]) due to higher relapse rates (32.7% versus 14.2% [P< 0.0005]). Important predictors of response were the levels of baseline viremia as well as the time to TMA negativity on treatment. Taking the simultaneous presence of low baseline viral load (<800,000 IU/mL) and a negative TMA test within the first 4 weeks as predictors for treatment response, SVR rates were comparable between both treatment schedules with an SVR probability of >80% obtained in patients treated for only 18 or 24 weeks. Conclusion: The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care. The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia. (HEPATOLOGY 2009.)

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