Anemia is primarily a result of hemolysis caused by ribavirin in addition to a myelosuppressive effect of IFN. These adverse events and their negative effect on quality of life during HCV therapy have been well documented.1-3, 18, 24 Several analyses have demonstrated a relationship between virologic response GSK458 research buy and the degree of changes in hematologic and weight parameters. In a study of previous

HCV nonresponders to prior therapy, patients who achieved at least a 1 log reduction in HCV RNA after 20 weeks of retreatment with PEG-IFN alfa-2a and ribavirin had a greater reduction in body weight, platelets, and white blood cells than null responders (<1 log10 reduction in HCV RNA levels by 20 weeks), possibly reflecting a systemic resistance to IFN in null responders.14 In a another analysis, treatment-naïve HCV genotype 1 patients treated with PEG-IFN alfa-2a and ribavirin who became HCV RNA undetectable at week 12 (i.e., complete early virologic response) experienced greater decreases in hematologic parameters compared with noncomplete early virologic response patients,

suggesting that viral response and hematologic changes are pharmacodynamic effects of IFN and GSK3235025 order ribavirin.15 In this post hoc analysis of treatment-naïve patients infected with HCV genotypes 1, 4, 5, or 6 who were treated with PEG-IFN alfa-2a and ribavirin, four mutually exclusive subgroups of virologic response were compared. Greater declines in neutrophil count, platelet count, hemoglobin level, and weight were demonstrated among patients

with responders (SVR, relapse, and breakthrough) compared this website with nonresponders after adjusting for the presence of cirrhosis, a known predictor of thrombocytopenia and nonresponse.25 However, among responders, no significant differences between patients with SVR, relapse, and breakthrough were observed. This supports the concept that achieving undetectable HCV RNA levels correlates with a similar host pharmacodynamic response to therapy regardless of whether the patient remains HCV RNA undetectable. Drug exposure and duration of therapy can affect both virologic response and pharmacodynamic effects. Up to a point, greater cumulative exposure results in greater virologic and pharmacodynamic effects. However, treatment discontinuation for nonresponse may lead to less total exposure to therapy in studies with week 12 or week 24 stopping rules. Three of the four studies1, 2, 8 in our analysis included nonresponse stopping rules, whereas the study comparing African American patients with Caucasian patients7 continued treatment for the full duration regardless of on-treatment response. Our analysis comparing virologic and pharmacodynamic responses of therapy among treatment completers accounts for the effect of drug exposure independent of the variable duration of therapy received.