|
Distinct hepatitis C virus kinetics in HIV-infected patients treated with ribavirin plus either pegylated interferon a-2a or a-2b
Presented by Eugenia Vispo, Spain.
E. Vispo1, P. Barreiro1, S. Rodriguez-Novoa2, J. Morello2, P. Labarga1, L. Martín-Carbonero1, I. Maida1, P. García-Gascó1, V. Soriano1
1Hospital Carlos III, Infectious Diseases, Madrid, Spain, 2Hospital Carlos III, Pharmacokinetic & Pharmacogenetic Unit, Madrid, Spain
Background: Pegylated interferon alpha (pegIFNa) -2a and -2b differ in their molecular weight and consequently in their pharmacokinetic properties, which might impact on their respective antiviral effects. Differences between pegIFNa molecules could be more pronounced in HIV-infected individuals, in whom response to hepatitis C virus (HCV) treatment is impaired.
Methods: All HCV/HIV patients included in PRESCO and EXTENT trials recruited at one referral centre were retrospectively analysed. In both trials, ribavirin (RBV) at doses of 1000-1200 mg/day was prescribed along with standard doses of pegIFNa-2a or -2b. 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 pegIFNa-2a versus -2b after adjusting for other variables.
Results: A total of 218 patients were examined, 138 on pegIFNa-2a and 80 on pegIFNa-2b. Baseline characteristics, including gender, CD4 count, HIV-RNA, HCV-RNA and liver fibrosis stage were comparable in both groups. Undetectable serum HCV-RNA at weeks 4, 12 and 24 was more frequently attained using pegIFNa-2a vs -2b (45 vs 27% [p=0.02]; 65 vs 45% [p=0.01]; and 75 vs 55% [p=0.01], respectively), regardless HCV genotype. Plasma RBV trough concentrations did not differ between groups. In multivariate analysis (OR [95% CI] p), HCV genotypes 2/3 (12.5 [3.45-33.33] <0.001), use of zidovudine (0.30 [0.11-0.85] 0.02), and treatment with pegIFNa-2a (2.12 [1.02-4.54] 0.04) were independent predictors of undetectable serum HCV-RNA at week 24.
Conclusions: The intrinsic antiviral effect is higher for pegIFNa-2a than for pegIFNa-2b in the HIV setting. An insufficient sustained antiviral effect at the end of weekly interval administration of pegIFNa-2b due to its shorter half-life could explain his observation.
|