Reply to Calcagno et al

TO THE EDITOR—In their comment regarding our meta-analysis, Calcagno et al make a very salient point with regard to the longer half-life of telaprevir and the impact this may have on its therapeutic robustness in the setting of less-thanoptimal adherence [1]. However, in the clinical trials examined by our metaanalysis, although adherence was not explicitly measured or reported, the discontinuation rates were very similar between the 2 agents and the rates of failure with resistance mutations were also low [2]. The subgroup of relapsers, in whom the difference between the 2 agents was detected, looked at a patient population with proven sensitivity to pegylated interferon and ribavirin and presumably with adherence that was adequate to result in an end-of-treatment response with standard of care. Therefore, it is unlikely that differences in patient adherence to treatment would account for the difference in efficacy detected by our analysis. That being said, the point regarding adherence is well made, especially as these treatment regimens are being rolled out into standard clinical practice and away from the idealized setting of a randomized clinical trial. The pharmacokinetic properties of telaprevir may allow some “forgiveness” in practice where adherence is likely to be lower than that found in a clinical trial setting. If there is indeed a benefit from a pharmacokinetic perspective in patients with poorer adherence, it would be expected that this would become more evident with increasing availability of real-world effectiveness data. In the setting of hepatitis C virus (HCV) treatment, there has been much work done looking at barriers to HCV treatment and care in both HCV-monoinfected and HCV/human immunodeficiency virus (HIV)–coinfected populations [3, 4]. Numerous factors have been identified relating to (1) HCV treatment and side effects, (2) provider experience with HCV patients, and (3) patient perceptions of treatment success and side effects [5]. Shorter durations of treatment and increased treatment success rates have been cited by patients as important factors in deciding whether to proceed with HCV treatment [6]. The shorter duration of triple therapy with telaprevir vs boceprevir and the resultant reduced duration of additive side effects may also influence the decision of which third agent to use, especially in the setting of concerns regarding patient adherence to treatment. In HIV care and other areas of therapeutics, pill burden and regimen complexity also have a role in adherence [7, 8]. The data on the validity of twice-daily dosing of telaprevir may allow reduced regimen complexity and improve adherence [9]. Our meta-analysis did not detect a difference in efficacy between the 2 agents in the overall populations, in keeping with international treatment guidelines, which do not state a preference for either agent [10]. Thus, along with host genetic and clinical factors, viral kinetics, and the pharmacokinetics of ribavirin, consideration of patient preference and adherence and the pharmacokinetics of the third agent will be important when it comes to individualizing the treatment paradigm for a particular patient.