Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients.

SUMMARY: Reluctance has been expressed about treating chronic hepatitis C in active intravenous (IV) drug users (IDUs), and this is found in both international guidelines and routine clinical practice. However, the medical literature provides no evidence for an unequivocal treatment deferral of this risk group. We retrospectively analyzed the direct effect of IV drug use on treatment outcome in 500 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study. Patients were eligible for the study if they had their serum hepatitis C virus (HCV) RNA tested 6 months after the end of treatment and at least one visit during the antiviral therapy, documenting the drug use status. Five hundred patients fulfilled the inclusion criteria (199 were IDU and 301 controls). A minimum exposure to 80% of the scheduled cumulative dose of antivirals was reached in 66.0% of IDU and 60.5% of controls (P = NS). The overall sustained virological response (SVR) rate was 63.6%. Active IDU reached a SVR of 69.3%, statistically not significantly different from controls (59.8%). A multivariate analysis for treatment success showed no significant negative influence of active IV drug use. In conclusion, our study shows no relevant direct influence of IV drugs on the efficacy of anti-HCV therapy among adherent patients.

Interferon alpha-2a plus ribavirin 1,000/1,200 mg versus interferon alpha-2a plus ribavirin 600 mg for chronic hepatitis C infection in patients on opiate maintenance treatment: an open-label randomized multicenter trial.

BACKGROUND: Many intravenous opiate users are infected with hepatitis C virus (HCV) but few are treated. Although this complies with various guidelines, virtually no published evidence supports such a recommendation. PATIENTS AND METHODS: In a multicenter study, HCV-infected patients in opiate maintenance treatment programs received interferon plus high- or low-dose ribavirin (1,000/1,200 mg or 600 mg). HIV-coinfected patients were not included. Endpoints were feasibility, efficacy, side effects, and reasons for dropout. RESULTS: Of the 420 patients who tested positive for HCV, 27 (6%) were enrolled; 393 (94%) either failed to meet the inclusion criteria or refused treatment. Virologic end-of-treatment response was achieved in 12/27 patients, and sustained response in 13/27 (48%). Response depended on viral genotype, not ribavirin dose. The two doses of ribavirin did not differ in their side effects. CONCLUSION: In a small fraction of HCV-infected intravenous drug users in an opiate maintenance treatment program, antiviral therapy was feasible, safe, and effective. The success rate was comparable to that achieved in controlled studies that excluded drug users.

Cytochrome P450 2D6 genotype and methadone steady-state concentrations.

A genetic polymorphism of cytochrome P450 2D6 has been described with the existence of poor (zero functional genes), extensive (one or two functional genes), and ultrarapid metabolizers (three or more functional genes). The authors measured the steady-state trough (R)- (i.e., the active enantiomer), (S)-, and (R,S)-methadone plasma levels in opiate-dependent patients receiving methadone maintenance treatment (MMT) and genotyped them for cytochrome P4502D6. The patients' medical records were reviewed to assess the outcome of the MMT with regard to the absence of illicit opiate consumption and to the absence of withdrawal complaints in ultrarapid and poor metabolizers. Of 256 patients included, 18 were found to be poor metabolizers, 228 to be extensive metabolizers, and 10 to be ultrarapid metabolizers. Significant differences were found between genotypes for (R)- (p = 0.024), (S)- (p = 0.033), and (R,S)-methadone (p = 0.026) concentrations to dose-to-weight ratios. For (R)-methadone, a significant difference was found between ultrarapid metabolizers and poor metabolizers (p = 0.009), with the median value in the former group being only 54% of the median value in the latter group. These results confirm the involvement of cytochrome P450 2D6 in methadone metabolism. Although the difference was nonsignificant (p = 0.103), 13 (72%) of the 18 poor metabolizers and only 4 (40%) of the 10 ultrarapid metabolizers were considered successful in their treatment. More studies are needed to examine the influence of the ultrarapid metabolizer status on the outcome of the MMT.

A continuing concern: HIV and hepatitis testing and prevalence among drug users in substitution programmes in Zurich, Switzerland.

Phase I of the Zurich Prometheus Study is a cross-sectional study focusing on an up-to-date serology for HIV and hepatitis B/C and associated risk factors for all clients in four participating clinics offering opiate substitution in Zurich, Switzerland. The mean age of the 603 respondents is 30.7 years (SD = 6.2) and 38% of them are women. Seventy-five per cent of the respondents have a history of injecting drug use (IDU), and over half have injected within the past six months. Laboratory-confirmed seroprevalence for HBV (50%) and HCV (57%) is twice that of HIV (24%). There is an 80% risk reduction for all three viral infections among those starting IDU after 1991--when harm reduction efforts were in full swing--compared to those who began before 1988--before clean needles were widely available. These findings suggest a strongly protective effect of harm reduction measures. But while a stabilization in HIV prevalence at 15% can be seen among drug users who started injecting after 1991, prevalence rates for HBV and HCV still remain several times higher. The prevalence data in this study support data showing continued high incidence rates for HBV and HCV, even among new injectors in the harm reduction era.