Early Virological Response Rates Research Articles

Management of hepatitis B and C in HIV co-infected patients.

Morbidity and mortality from co-morbid hepatitis B (HBV) and hepatitis C (HCV) infection in HIV co-infected patients are increasing; hence, the management of HIV and HBV or HCV co-infected individuals is now one of the most challenging clinical management issues. Less than 10% of all HIV-infected patients show markers of chronic HBV infection. Hepatitis B in HIV co-infected patients is characterized by high levels of HBV replication and a high risk for cirrhosis. Treatment of HBV with lamivudine (3TC) remains the best treatment option at this time. Initial results of studies of adefovir or tenofovir, however, demonstrate good antiretroviral efficacy, even in patients with 3TC-resistant HBV. In Europe, it is estimated that approximately 30% of HIV-infected individuals are co-infected with HCV. HIV accelerates HCV liver disease especially when HIV-associated immune deficiency progresses. Within 10-15 years of initial HCV infection, 15-25% of patients who are co-infected with HIV develop cirrhosis compared with 2-6% of patients without HIV infection. With the introduction of pegylated interferon in combination with ribavirin, promising treatment options have become available for HIV/HCV co-infected patients leading to early virological response rates of approximately 50%. The high number of HIV/HCV and HIV/HBV co-infections, as well as the much more unfavorable course of HBV and HCV in these patients, underlines the need to establish treatment strategies for HBV and HCV in HIV co-infected individuals.

Steatosis influences the early virologic response rate in patients with chronic hepatitis C infection

a virological response (undetectable [<600 IU/ml.] or a 2dog0 drop in HO/RNA serum concentrations) treatment week 4 The most frequently reported adverse events included headache myalgia, py~'exia, tatigue and anorexia: most were mild or moderate in intensity. No signs of opioid withdrawal were observed No patient modified methadone or PEG-IFN doses during the sudy One subject withdrew prematurely due to poor venous access. Conclusions: PEGqFN monotberapy is well-tolerated by CHC patients receiving MMT. PEGIFN and methadone do not significantly alter the PK of each respective therapy. Biologic response as assessed 2,5 -OAS activity was similar to that in healthy subjects. HCV RNA dechne was similar to that seen in CHC patients not receiving MMT These data suggest that MMT does not impair the antiviral activ W of PEG-IFN

Two PKR inhibitor HCV proteins correlate with early but not sustained response to interferon

Background & Aims: The NS5A and the E2 proteins of hepatitis C virus (HCV)-1b can bind and inhibit in vitro the interferon (IFN)-induced cellular kinase PKR. The role of such interaction in modulating the antiviral effect of IFN is still controversial. We have analyzed the E2 and the NS5A sequences in HCV-1b–infected patients treated with IFN to assess whether and how different combinations of wild-type and mutant proteins correlated with early and long-term virological response. Methods: In 30 patients, sequences of pretreatment and on-treatment E2-PePHD and NS5A-PKR binding domain (including the putative ISDR) were analyzed in parallel by sequencing cDNA–polymerase chain reaction products and up to 25 independent clones. Results: The E2-PePHD sequence was highly conserved with a homogeneous quasispecies and was identical in 29 of 30 cases with no association with the pattern of response and no evidence of evolution during therapy. Patients with a mutated NS5A-ISDR had a higher rate of early virological response (67%) than cases with wild-type ISDR (17%). This association was lost in long-term responders (33% vs. 17%). Conclusions: Although the highly conserved E2-PePHD motif might contribute to reduce IFN responsiveness, variations within this region do not seem to play a role in modulating IFN sensitivity. The NS5A-ISDR sequence influenced the early, but not the sustained response, to IFN, suggesting that other factors may be more important for the long-term outcome of therapy.GASTROENTEROLOGY 2000;119:1649-1655