Effect of HCV viral dynamics on treatment design: lessons learned from HIV

Abstract

Viral load measurements provide an indication of viral replication, and thereby serve as a valuable tool to guide the initiation of therapy and subsequent changes. Plasma human immunodeficiency viral load strongly predicts the rate of decrease in CD4+ lymphocyte count, and progression to AIDS and death. Furthermore, the efficacy of antiretroviral therapy can be assessed by monitoring changes in plasma human immunodeficiency viral load. Similarly, viral load provides valuable information about the natural history of the hepatitis C virus infection. Hepatitis C viral load can be used to predict the likelihood of response to standard interferon-alpha treatment and other interferon-alpha regimens and to monitor treatment efficacy. Increased understanding of the natural history of the hepatitis C virus infection and the nature of resistance to interferon-alpha therapy suggests that effective treatment regimens must maintain serum levels of interferon-alpha. Ideally, interferon-alpha serum levels should provide constant pressure on the virus and should prevent viral rebound, thereby avoiding continued viral replication and minimizing the potential for emergence of resistant quasi-species. Current regimens designed to address these points include early aggressive intervention, combination drug regimens, prolonged maintenance, and novel interferons. By enabling the design and rapid assessment of new treatment regimens, viral load measurement will revolutionize the clinical management of the hepatitis C virus infection, as it has the HIV.

Indicators and predictors of response to anti‐viral therapy in chronic hepatitis C

“…Quantitative tests of viral load are crucial for predicting the response to IFN and guiding the duration of therapy 18 . Quantitative tests use two methods: target amplification methods (based on quantitative polymerase chain reaction) and signal amplification methods (such as the branched DNA assay).…”

SCH 503034, a Mechanism-Based Inhibitor of Hepatitis C Virus NS3 Protease, Suppresses Polyprotein Maturation and Enhances the Antiviral Activity of Alpha Interferon in Replicon Cells

“…The current standard of care for chronic HCV infection is pegylated alpha interferon (IFN-␣) alone or in combination with oral ribavirin (28). Although this combination therapy is reasonably successful (ϳ70 to 80% sustained virological response [SVR]) with the majority of genotypes (1,2,4,5), its efficacy against genotype 1, the major genotype affecting North America, Europe, and Japan, is moderate at best, with only about 40% of treated patients showing SVR (16,48). Lack of a complete response, relapse following therapy, and premature termination of therapy due to intolerability of side effects contribute to this poor eradication rate observed among genotype 1-infected individuals and underscore the need for new anti-HCV therapeutics.…”

Predictors of Response to Therapy for Chronic Hepatitis C

“…Detailed analysis of viral dynamics during antiviral therapy is useful in understanding pathogenesis and in guiding therapy. 34 Much information has been derived from studies of the kinetics of HCV decline after initial doses of interferon. The available data indicate that the response to interferon can be divided into at least two phases: the induction period and the maintenance period.…”