Our hypothesis is also supported by the lack of relationship between pegIFN-�� 2a plasma 17-AAG levels and the rate of viral response, despite those being lower than that observed previously with pegIFN-�� 2a at 180 ��g once weekly (2467; range, 757 �C 5136 vs. 4762 pg/mL; range, 1419 �C 6451) [14]. However, while a treatment duration of 20 weeks after attaining undetectable serum HCV-RNA seems adequate in patients achieving RVR regardless of their baseline HCV-RNA (in fact, both relapsing patients had baseline viremias<5000 UI/mL), the high relapse rate in patients with no RVR suggests that extending treatment to only 20 weeks after achieving negativization of viremia is not sufficient and thus a longer treatment period is needed.
No relationship was observed between Rbv plasma levels and viral responses during therapy or SVR rate, similar to results in our previous study [14]. Moreover, we did not find any relationship between the administered dose per kg of Rbv and its plasma levels achieved at just 12 hours after drug intake. Therefore, we believe the current recommendation of dosing Rbv in mg/kg according to the patient’s weight is still a matter of debate, particularly in G2/3 in which doses of 400 and 800 mg/day might produce equivalent SVR rates in patients infected with HCV G3 [26]. Likewise, we observed no relationship between rs129679860 IL28B genetic polymorphisms and virological responses to pegIFN-�� 2a plus Rbv in our patients with CHC G3, as has been previously reported in both G3 monoinfected and HCV/HIV-coinfected patients [27]�C[29], although the existing data on this issue are not entirely homogeneous [30].
Regarding the incidence of toxicity, it is remarkable that both clinical and laboratory AEs were just mild and did not motivate dose reductions in patients receiving the 135 ��g dose. Four out of the 8 cases of AEs which motivated treatment interruption were considered unrelated to study treatment. Thus, the rate of drop-outs due to treatment-related toxicity was only 6.9%, which compare favorably with previous studies in which the rate of serious AEs varied between 10 and 18% [4], [5], [9], [11]. Moreover, these drop-outs were mainly caused by poor tolerance rather than by the severity of the AEs. The main limitation of our study is the fact that it is a single-arm trial in which the results were compared with those observed in earlier clinical trials.
However, we believe such a study had to be carried out prior to the Carfilzomib design of a randomized controlled trial allowing for a one-to-one comparison between efficacy and safety of weekly 135 and 180 ��g doses of pegIFN-��-2a in G3 HCV/HIV-coinfected patients. Furthermore, a high drop-out rate (18.9%), mainly due to low grade AEs and those unrelated to the study medication, penalized the intention-to-treat analysis results.