Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

Abstract

Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and 4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.

Peg‐interferon and ribavirin treatment in HIV/HCV co‐infected patients in Thailand: efficacy, safety and pharmacokinetics

“…We showed that at week 8 of treatment, ribavirin reached steady‐state, which fits the long elimination half‐life of 300 h . The steady‐state ribavirin plasma concentrations found in this study were in the same range as previously published in HIV/HCV co‐infected patients . However, these plasma concentrations remained lower than reported ribavirin plasma concentrations in mono‐infected patients .…”

“…This could be driven by the increasing number of patients of which ribavirin plasma concentrations were available towards weekend 48. The relation between ribavirin plasma concentrations and SVR remains controversial, as both negative and positive results have been published about this topic . These inconsistent results might be caused by, for example, differences in treatment, heterogeneity of populations, variation in analytical assays and small sample sizes.…”

Telaprevir and Ribavirin Interaction: Higher Ribavirin Levels Are Not Only Due to Renal Dysfunction during Triple Therapy

“…Dropout data were included up to the last available visit for individuals on treatment. The Rbv levels before week 4 were excluded from the analysis, as we had previously observed that Rbv concentrations were significantly lower dur-ing the first 2 weeks of treatment and became stable from week 4 onward (13).…”

“…During the triple-therapy course, Rbv plasma concentrations were compared between the period when Rbv was given concomitantly with TVR (weeks 0 to 12) and the period after TVR discontinuation (week 13 forward), using analyses of repeated measures. Additionally, the Rbv levels during TT were compared with both those observed in the same subjects during a previous DT course and those for a cohort of 125 adult Caucasian HCV-1/HIV-coinfected patients treated with pegIFN-␣ plus Rbv, without Rbv dose reduction during the DT course, which were measured by reverse-phase high-performance liquid chromatography in the same hospital (13).…”

“…However, all studies agree about the association between Rbv plasma levels and the occurrence and severity of anemia (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). In the recent past, the NS3/4A protease inhibitors boceprevir and telaprevir (TVR) were incorporated into the armamentarium for the treatment of chronic hepatitis C virus genotype 1 (HCV-1) infection.…”