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.
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.
Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
A
A
Torres-Cornejo
R
R
Ruiz-Valderas
L
L
Jimenez-Jimenez
C
C
Abad-Molina
A
A
Gutierrez-Valencia
P
P
Viciana
L F
LF
Lopez-Cortes
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
IL28B polymorphisms; pharmacodynamics; response to therapy