Distinct hepatitis C virus kinetics in HIV-infected patients treated with ribavirin plus either pegylated interferon alpha2a or alpha2b.
BACKGROUND
Pegylated interferon (PEG-IFN) alpha2a and alpha2b differ in their pharmacokinetic properties, which might have an effect on their antiviral effects against hepatitis C virus (HCV). Differences between PEG-IFN-alpha molecules could be more pronounced in HIV-coinfected individuals, in whom response to HCV treatment is impaired.


METHODS
All HCV-HIV-coinfected patients included in PRESCO and EXTENT trials recruited at one referral centre were retrospectively analysed. In both trials, ribavirin (RBV) 1,000-1,200 mg/day was prescribed together with standard doses of PEG-IFN-alpha2a or -alpha2b. The attainment of serum HCV RNA <10 IU/ml at weeks 4, 12 and 24 was assessed. On-treatment analyses were made to estimate the intrinsic potency of PEG-IFN-alpha2a versus -alpha2b.


RESULTS
A total of 218 patients were examined, 138 on PEG-IFN-alpha2a and 80 on PEG-IFN-alpha2b. Baseline characteristics were comparable in both groups. Undetectable serum HCV RNA at weeks 4, 12 and 24 was more frequently attained using PEG-IFN-alpha2a than -alpha2b (45% versus 27% [P=0.02]; 65% versus 45%/ [P=0.01]; and 75% versus 55%/ [P=0.01], respectively), regardless of HCV genotype. Plasma RBV levels did not differ between groups. In multivariate analysis, HCV genotypes 2/3 (odds ratio [OR] 12.5; 95% confidence interval [95% CI] 3.45-33.33; P<0.001), use of zidovudine (OR 0.30; 95% CI 0.11-0.85; P=0.02) and treatment with PEG-IFN-alpha2a (OR 2.12; 95% CI 1.02-4.54; P=0.04) were independent predictors of undetectable HCV RNA at week 24. Conversely, the incidence of serious adverse events was more common with PEG-IFN-alpha2a than -alpha2b (13.2% versus 3.6%; P=0.018).


CONCLUSIONS
The antiviral effect against HCV seems to be greater for PEG-IFN-alpha2a than -alpha2b in the HIV setting. A shorter half-life of PEG-IFN-alpha2b could explain this finding.
Vispo
Eugenia
E
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Barreiro
Pablo
P
Rodriguez-Nóvoa
Sonia
S
Morello
Judit
J
Labarga
Pablo
P
Martín-Carbonero
Luz
L
Maida
Ivana
I
García-Gascó
Pilar
P
Soriano
Vincent
V
D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a