Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education.
Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.
Once HCV treatment is started, initial viral kinetics are helpful in predicting treatment outcome with certain regimens. Patients who have undetectable HCV RNA by Week 4 of therapy—whether with protease inhibitor–based triple therapy or with peginterferon/ribavirin alone—are very likely to achieve SVR. By contrast, those who still have detectable HCV RNA levels by Week 12 of therapy have very low likelihood of obtaining SVR with boceprevir or telaprevir.
Early viral responses are influenced by all pretreatment factors, and therefore once treatment has started, prognosis is almost entirely dictated by the rapidity of decline in HCV RNA. As an illustration of this point, the IL28B genotype loses predictive value for SVR after controlling for treatment response. A patient with the unfavorable non-CC genotype who achieves a rapid virologic response (which is less likely but still possible) has a better chance of obtaining an SVR than a patient with a favorable CC genotype who does not achieve a rapid virologic response.[178,179]
In patients receiving boceprevir or telaprevir, early responses remain critical determinants of treatment outcome. If used, the peginterferon/ribavirin lead-in phase provides useful information about interferon responsiveness and likelihood of achieving SVR. Establishing HCV RNA response after a lead-in phase in patients receiving these agents may help patients and practitioners decide whether to proceed with therapy with a protease inhibitor after the initial 4 weeks of treatment. Early treatment responses are particularly important for identifying treatment failure. Patients who fail to rapidly suppress virus to low levels during triple therapy are very unlikely to respond to therapy and continuing treatment will simply increase their risk for selection of additional resistance mutations. The prescribing information for boceprevir and telaprevir state that patients receiving boceprevir-based therapy who have HCV RNA ≥ 1000 IU/mL at Week 8, and patients with HCV RNA > 1000 IU/mL at Week 4 of treatment with telaprevir, peginterferon, and ribavirin should stop all therapy.[180,181]
Patients receiving simeprevir with peginterferon plus ribavirin whose HCV RNA is ≥ 25 IU/mL at Week 4 of treatment should discontinue all therapy, and peginterferon plus ribavirin should be stopped in patients with HCV RNA ≥ 25 IU/mL at Week 12 or 24.
As almost all patients who receive newer DAA regimens achieve undetectable HCV RNA fairly rapidly, monitoring virologic response with a view to identifying nonresponders is less relevant in this setting. There are no futility rules for use of ombitasvir/paritaprevir/ritonavir plus dasabuvir, ledipasvir/sofosbuvir, or sofosbuvir, although sofosbuvir should be discontinued if other agents used in combination with sofosbuvir are permanently discontinued. Patients receiving DAA regimens who do not have undetectable HCV RNA at Week 4 of treatment should be assessed for problems with medication adherence. It is preferable to continue therapy in such cases, as many patients who do not suppress HCV RNA early on are still likely to achieve SVR if they complete the treatment course.