High rate of non-response and relapse associated with peginterferon-alfa monotherapy for the treatment of acute hepatitis C in HIV-infected patients

摘要

Background: The incidence of acute hepatitis C virus infection (HCV) in patients infected with human immunodeficiency virus (HIV) is rising. Because of low patient numbers and a wide variety of inclusion criteria between studies, the optimal treatment regimen is under debate. We advocated peginterferon-alfa monotherapy (pegIFN-α) for acute HCV in HIV-coinfected patients (Arends-JE et al. AIDS 2008; 22(11):1381-138). Methods: In HIV-infected patients acute HCV was diagnosed by anti-HCV serology and quantitative PCR (HCV-RNA), in combination with clinical signs or elevated alanine aminotransferase (ALAT), and a negative serology within 1 year prior to diagnosis. All patients started treatment with peginterferon alfa-2a (180 μgr /weekly) and continued if a rapid viral response at week 4 (RVR, i.e. HCV-RNA 2log10decrease or undetectable HCV-RNA at week 12 of therapy. Results: Until July 2009 a total of 23 HIV-patients were diagnosed in both centers (UMCU and UMCG) with acute HCV-infection (17 genotype 1 and 6 genotype 4) of whom 19 started peginterferon alfa-2a monotherapy. A RVR was reached by 7 patients (37%) while 10 patients (53%) achieved an EVR. 2 patients reached an EVR with addition of ribavirin from week 4 onwards. Nine patients (47%) were non-responders with a less than 2log10 drop in HCV-RNA at week 12 with 1 patient receiving additional ribavirin from week 4 onwards. All non-responders discontinued treatment at week 12 of therapy. With respect to time between seroconversion and start of therapy, baseline HCV-RNA viral load, maximum ALAT reached, baseline CD4 count and HIV-RNA viral load, no statistical differences were observed between responders (RVR and EVR) and non-responders. Interestingly, 5 out of 7 patients achieving a RVR also completed their 24-weeks of therapy. Unexpectedly, 3 patients in this group experienced a relapse of their HCV-infection. This relapse was confirmed by sequence analysis of the NS5B-region comparing the baseline quasi-species pool with the relapse strains. Conclusion: Peginterferon-alfa monotherapy resulted in a high percentage of non-responders. Furthermore, relapse of HCV-infection in patients achieving a RVR, was common after completion of treatment. Combination with ribavirin seems to be essential in HIV-infected patients with acute HCV infection.