A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.

Treatment with peg-IFN and ribavirin is relatively well-tolerated in HIV/HCV-co-infected patients, although new side-effects, including pancreatitis and severe weight loss, may result from the interaction of ribavirin with antiretroviral drugs. Overall, therapy provides cure to one third of patients, a rate significantly lower than that seen in HCV-monoinfected individuals. Given that relapses are common, extended periods of therapy should be investigated.

No abstract

Ribavirin (RBV) in combination with pegylated interferon alpha (pegIFN) is currently the standard treatment of hepatitis C virus (HCV) infection. The development of anemia requires a reduction in RBV doses in a substantial proportion of patients, limiting their chances of treatment response. The primary goal of this study was to assess if early monitoring of RBV plasma levels could help to predict anemia as well as early HCV RNA response in HIV/HCV-coinfected individuals. The secondary goal was to evaluate if antiretroviral drugs might influence RBV plasma levels. Plasma RBV concentrations were measured at weeks 4 and 12 in 98 HIV/HCV-coinfected individuals who initiated therapy with pegIFN-2a (180 microg/wk) plus RBV (800-1200 mg/d). RBV plasma levels correlated with RBV dose per kilogram of body weight (P = 0.02). Larger drops in hemoglobin levels were independently associated with higher RBV plasma levels and zidovudine (ZDV) use (P < 0.001). Likewise, higher RBV levels (P = 0.007) and HCV genotype 3 (P < 0.001) were found to be independent predictors of virologic response at week 4. Similar findings were obtained at week 12. Patients receiving ZDV concomitantly showed significantly higher RBV plasma concentrations compared with those who did not (3.28 mug/mL vs. 2.51 mug/mL; P = 0.002). RBV levels were not significantly altered by the coadministration of other nucleoside/nucleotide analogues. In summary, RBV plasma levels correlate with the development of anemia and with the achievement of an early virologic response. Therefore, early therapeutic drug monitoring might help to tailor RBV dosages, improving the efficacy and safety of anti-HCV treatment.

The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.