This pilot study was aimed to evaluate two hypothesis; first, the viral efficacy of a pegIFN-α-2a dose lower than the standard of care, and, second, if a treatment duration of 20 weeks after attaining undetectable serum HCV-RNA was sufficient in G 3 HCV/HIV-coinfected patients. Regarding the first hypothesis, the dose-ranging studies with both formulations of PegIFN-α showed that lower than the standard doses (90 or 135 µg weekly for pegIFN-α 2a, and 0.75 µg/kg weekly for pegIFN-α 2b) achieved similar SVR rates in HCV monoinfected patients with G 3, both as a single agent 
and in combination with Rbv 
. However, to date there are no data available, to our knowledge, on the use of low doses of PegIFN-α in HCV/HIV coinfected patients.
Our results suggest that pegIFN-α-2a given at 135 µg once weekly might be as effective as the standard 180 µg dose, when administered together with 800 mg daily of Rbv in G3 HCV/HIV-coinfected patients, since both on treatment RVR and EVR rates in our study (51.9%, and 94.3%, respectively) were similar to those observed in other studies as the Apricot trial (37%, and 88%, respectively) 
, and our previous study (RVR, 58.3%; EVR, 97.5%) in which similar patients were treated with weekly 180 µg pegIFN-α 2a 
. These results are despite the use of a stricter criterion for a negative HCV viremia in the current study (≤15 UI/mL by quantitative PCR assay vs.<50 UI/mL by qualitative PCR). In fact, five patients in our study had viremia levels between 18 and 48 IU/mL at week 4, which would have rated them as rapid responders by qualitative methods. Unfortunately, there are no other studies on pegIFN-α 2a plus Rbv (800 mg/day) in HIV-coinfected patients with CHC G3 which reported EVR rates on treatment for comparison. In the Presco study a SVR rate of 79.3% was observed after standard pegIFN-α-2a 180 µg dose plus higher Rbv dose (1000–1200 mg/day) instead a flat dose of 800 mg/day 
Our hypothesis is also supported by the lack of relationship between pegIFN-α 2a plasma levels and the rate of viral response, despite those being lower than that observed previously with pegIFN-α 2a at 180 µg once weekly (2467; range, 757 – 5136 vs. 4762 pg/mL; range, 1419 – 6451) 
. 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 
. 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 
Likewise, we observed no relationship between rs129679860 IL28B genetic polymorphisms and virological responses to pegIFN-α 2a plus Rbv in our patients with CHC G3, as has been previously reported in both G3 monoinfected and HCV/HIV-coinfected patients 
, although the existing data on this issue are not entirely homogeneous 
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 µg 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% 
. 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 design of a randomized controlled trial allowing for a one-to-one comparison between efficacy and safety of weekly 135 and 180 µg doses of pegIFN-α-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.
In conclusion, our results suggest that weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with lower incidence of severe AEs, supporting the design of a randomized controlled trial allowing for a one-to-one comparison between efficacy and safety of weekly 135 and 180 µg doses of pegIFN-α-2a in G3 HCV/HIV-coinfected patients. Our data evidence that neither the rs129679860 IL-28B genetic polymorphisms nor plasma pegIFN-α-2a or Rbv levels influence the virological responses in G3 HCV/HIV-coinfected patients. On the other hand, while a 24-week treatment duration appears to be appropriate in patients achieving negative viremia on week 4, extending treatment duration up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR, and therefore a more prolonged treatment is warranted in these patients.