Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study.

BACKGROUND/AIMS: Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects. METHODS: Patients with genotypes 1 and 4 were treated for 48 weeks with Pegasys 180 microg/week plus Copegus 1000-1200 mg/day according to body weight; patients with genotypes 2 and 3 for 24 weeks with Pegasys 180 microg/week plus Copegus 800 mg/day. RESULTS: 132 patients were enrolled in the study: 85 HCV mono-infected (38: genotypes 1 and 4; 47: genotypes 2 and 3), 47 HIV-HCV co-infected patients (23: genotypes 1 and 4; 24: genotypes 2 and 3). In an intention-to-treat analysis, SVR for genotypes 1 and 4 was observed in 58% of HCV mono-infected and in 13% of HIV-HCV co-infected patients (P = 0.001). For genotypes 2 and 3, SVR was observed in 70% of HCV mono-infected and in 67% of HIV-HCV co-infected patients (P = 0.973). Undetectable HCV-RNA at week 4 had a positive predictive value for SVR for mono-infected patients with genotypes 1 and 4 of 0.78 (95% CI: 0.54-0.93) and of 0.81 (95% CI: 0.64-0.92) for genotypes 2 and 3. For co-infected patients with genotypes 2 and 3, the positive predictive value of SVR of undetectable HCV-RNA at week 4 was 0.76 (95%CI, 0.50-0.93). Study not completed by 22 patients (36%): genotypes 1 and 4 and by 12 patients (17%): genotypes 2 and 3. CONCLUSION: Genotypes 2 or 3 predict the likelihood of SVR in HCV mono-infected and in HIV-HCV co-infected patients. A 6-month treatment with Peginterferon alpha 2a plus ribavirin has the same efficacy in HIV-HCV co-infected patients with genotypes 2 and 3 as in mono-infected patients. HCV-RNA negativity at 4 weeks has a positive predictive value for SVR. Aggressive treatment of adverse effects to avoid dose reduction, consent withdrawal or drop-out is crucial to increase the rate of SVR, especially when duration of treatment is 48 weeks. Sixty-one percent of HIV-HCV co-infected patients with genotypes 1 and 4 did not complete the study against 4% with genotypes 2 and 3.

Barriers to interferon-alpha therapy are higher in intravenous drug users than in other patients with acute hepatitis C.

BACKGROUND/AIMS: Treatment with interferon-alpha (IFN-alpha) may eradicate HCV in most acute hepatitis C patients, thus preventing chronic hepatitis and avoiding less efficacious combination therapy. METHODS: In a prospective study, we evaluated the impact of barriers to successful start and completion of treatment of acute and subacute (<12 months from infection) hepatitis C with pegylated IFN-alpha2b, 1.5 microg/kg, QW, for 24 weeks. RESULTS: Out of 27 patients (22 were active intravenous drug users [IVDU]), 5 cleared HCV spontaneously. Antiviral treatment was indicated in 22 patients: six refused therapy for fear of side effects, whereas two others were lost to observation. Eight patients completed the treatment or received >80% of the scheduled drug: seven (88%) were sustained virological responders 24 weeks after the end of treatment. Six patients (all IVDU) stopped prematurely due to side effects: only one had a sustained virological response. Based on an intent-to-treat analysis, and considering all 14 patients in whom at least one dose of drug was administered, only 8 (57%) became sustained virological responders. CONCLUSIONS: Treatment of acute hepatitis C with pegylated IFN-alpha is highly beneficial, but its effectiveness is affected by a poor rate of acceptance and/or adherence to currently available regimens, especially in IVDU and women.