To our knowledge, this study is the first, outside of clinical trials, to evaluate the relationship between adherence to combination HCV therapy during the initial 12 weeks of treatment and virologic outcomes. Adherence of
85% to pegylated IFN and ribavirin treatment, measured by pharmacy refill data, was associated with increased HCV suppression and EVR. Decreases in HCV load became even greater when patients had
85% adherence to their regimen and were prescribed the recommended weight-based ribavirin dosage throughout the initial 12 weeks of treatment. Adherence to pegylated IFN treatment was statistically greater than adherence to ribavirin treatment, but the magnitude of this difference was small and unlikely to be clinically significant. Moreover, adherence levels to the 2 anti-HCV medications were comparable for individuals. Finally, patients with a history of HIV infection, depression, posttraumatic stress disorder, or alcohol abuse did not have poorer adherence, compared with those without a history of these conditions.
This study demonstrates that maintaining high levels of adherence to pegylated IFN and ribavirin regimens throughout the initial 12 weeks of therapy is associated with better virologic outcomes, particularly when recommended weight-based ribavirin dosages are prescribed and maintained. Thus, in addition to administering optimal dosages of anti-HCV medications, providers should also encourage high levels of adherence to both anti-HCV medications before and throughout treatment to ensure maximum response to therapy. Identifying suboptimal (i.e., <85%) adherence to pegylated IFN and/or ribavirin therapy with use of pharmacy refill data could allow HCV treatment providers to help patients improve their adherence during treatment, which could help improve virologic response rates. Although interventions to increase adherence to HCV therapy have not been tested, providers could ask patients about barriers to adherence (e.g., forgetting doses) and help them identify potential solutions (e.g., using reminder alarms).
Our findings suggest that HCV suppression does not increase with adherence to pegylated IFN and ribavirin therapy >85%. In addition, the proportion of patients with an EVR was similar for all adherence levels
85%. It is possible that 85% adherence might represent a threshold adherence level below which virologic suppression is reduced. We were unable to determine the presence of a threshold statistically because of the small numbers of patients with adherence <85%. Future studies will need to determine whether such a threshold exists and whether it occurs at this 85% adherence level. If confirmed, this threshold would represent a target for treatment adherence interventions.
Our study also examined whether certain subgroups of patients demonstrated lower levels of adherence. Patients with a history of depression, posttraumatic stress disorder, and alcohol abuse are considered to be at risk for nonadherence to treatment, but our results did not demonstrate poorer adherence among patients in these subgroups. These findings should not be attributed to selection bias, because the characteristics of excluded patients were similar to those of patients who were included. Because of this finding, HCV providers should not be reluctant to initiate treatment for these patients because of a perceived risk of nonadherence to treatment. Additional risk factors for nonadherence to HCV therapy should be examined to determine high-risk subgroups and whom to target with interventions to improve adherence.
Our results have several potential limitations. First, the retrospective study design did not permit HCV load testing at the same time during treatment for each patient, but we required week 12 viral loads to have been obtained in a narrow window to reduce misclassification of outcomes. Second, although it is possible that we could have misclassified adherence as good for some patients who had late first and/or second refills of anti-HCV medications but on-time third refills, we still found a strong association between our adherence measure and virologic outcomes, which suggests that the amount of misclassification of adherence was minimal. Third, by including only patients who had a follow-up viral load measurement obtained between weeks 11 and 13, we may have selected individuals who were more likely than others to be adherent to their anti-HCV regimen. However, the characteristics of patients who were excluded from the study were similar to those of patients who were included; thus, these exclusions should not have altered our conclusions. Fourth, all measures of treatment adherence are imperfect. However, the potential misclassifications of the measure that we used would tend to bias results to show no difference, and we still found significant associations. Finally, only US veterans were included in this study, which potentially limits the generalizability of our results; however, it is unlikely that the relationship between adherence and virologic response is different in other populations.
In conclusion, providers should consider poor treatment adherence as a possible cause of virologic nonresponse during HCV therapy. Future studies should evaluate risk factors for poor adherence and monitor changes in the magnitude of adherence beyond the initial 12 weeks of HCV therapy to determine the optimal timing and nature of interventions to maximize adherence.