Early HCV dynamics on Peg-interferon and ribavirin in HIV/HCV co-infection:: indications for the investigation of new treatment approaches

Objectives: To describe the 28-day hepatitis C virus (HCV) kinetics under Pegylated-interferon (Peg-IFN) + ribavirin (RBV) therapy in HlV/HCV co-infected patients. To evaluate the predictive value of early virological response (EVR) of achieving a sustained virological response (SVR). To investigate the baseline mutations in the interferon sensitivity determining region (ISDR)(2209-2248) in the non-structural 5A protein of HCV according to genotype. Methods: Open, prospective trial including 28 co-infected patients with directly observed treatment with Peg-IFN + RBV. We assessed the predictive values of EVR (greater than or equal to2 log(10) of HCV decay or a negative qualitative test) at days 1, 7, 28 and in week 12 of the SVR. Results: The SVR in an intention-to-treat analysis was 28.6% (genotype 1, 1/13; genotype 3, 6/10; genotype 4, 1/5). Patients who reached SVR presented a significantly faster HCV plasma viral load reduction compared to non-responders from the first 24 h [-1.06 log(10) (interquartile range, -1.7 to -0.4) versus -0.05 log(10) (interquartile range, -0.4 to +0.14) respectively; P=0.002]. The median HCV viral load at week 12 was significantly different from that at baseline in responder and transient responders but not in non-responder patients. The positive predictive value was 100% within the first month and the best negative predictive value was 92% and 88.8% at weeks 4 and 12 respectively. The only genotype 1 responder patient had eight mutations in ISDR2209-2248. Conclusions: A very early HCV viral decay is observed in responder patients. An early virological response assessment at week 4 and 12 might be a useful tool in the clinical management of the co-infected population. (C) 2004 Lippincott Williams Wilkins.