Background:  Pegylated interferon (pegIFN) + ribavirin (RBV) is the recommended therapy for chronic hepatitis C virus (HCV) in HIV⁺ patients. Pharmacokinetic differences between the 2 available pegIFN molecules, a-2a and a-2b, might influence their antiviral activity.

Methods:  All consecutive HCV/HIV-co-infected patients who initiated treatment with pegIFNa (-2a or -2b) + RBV (1000 to 1200 mg/day) at our institution during 2005 were identified. Patients with prior IFN experience were excluded. We assessed 3 main virological end-points:  rapid virological response, defined as HCV RNA <10 IU/mL at week 4; early virological response, defined as ³2 log drop in HCV RNA at week 12; and week 24 HCV RNA <10 IU/mL. Baseline liver fibrosis was estimated in all patients using transient elastometry. Plasma RBV levels were measured by high-performance liquid chromatography (HPLC) at week 12.

Results:  A total of 104 patients were identified; 72 started pegIFNa-2a and 32 pegIFNa-2b. Main characteristics of the 2 groups were similar. Mean age, 43.2 and 43.5 years; male gender, 74 and 75%; mean body mass index, 23 and 22 kg/m²; mean CD4 count, 581 and 572 cells/mL; HIV RNA <50 copies/mL, 69 and 75%; mean HCV RNA, 6.05 and 6.13 log IU/mL; HCV RNA >800,000 IU/mL, 60 and 69%; HCV genotypes 1-4, 67 and 63%; mean hepatic stiffness, 9.2 vs 10.6 kPa (p = ns for each variable). Mean RBV plasma levels at week 12 were 2.4±1.1 and 2.3±1.0 mg/mL (p = ns). In an intent-to-treat analysis, mean HCV RNA decay was 2.6 and 2.6 log IU/mL at week 4; 4 and 3.9 log IU/mL at week 12; 4.3 and 4.4 log IU/mL at week 24 (p = ns).

Per protocol (on treatment analysis) virological responses were comparable for pegIFNa -2a and -2b:  rapid virological response, 25 and 23%; early virological response, 85 and 86%; week 24 undetectability, 81 and 76% (p = ns). Considering only HCV genotypes 1-4: rapid virological response, 17 and 16%; early virological response, 78 and 82%; week 24 undetectability, 77 and 69% (p = ns). For HCV genotypes 2-3: rapid virological response, 47 and 33%; early virological response, 100 and 91%; week 24 undetectability, 87 and 87% (p = ns). In patients with HCV RNA >800,000 IU/mL: rapid virological response, 24 vs 14%, early virological response, 82 vs 85%, and week 24 undetectability, 79 vs 81%, for pegIFNa -2a vs -2b (p = ns). The best threshold for RBV plasma concentrations at week 12 to predict undetectability at week 24 was 2.1 mg/mL for both pegIFNa -2a and -2b (positive predictive value, 82%).

Conclusions:  The intrinsic antiviral activity of pegIFNa-2a and pegIFNa-2b seems to be comparable in HCV/HIV-co-infected patients during the first 24 weeks of therapy. The attainment of high RBV plasma concentrations, rather than the pegIFN modality, is the main determinant for virological success of anti-HCV therapy.