Safety And Efficacy Of The Combination Of GLS4JHS And Ritonavir In Patients With Chronic HBV Infection

Objective:GLS4JHS can interfere with the assembly of hepatitis B virus(HBV)core particles and is a new generation of two hydrogen pyrimidine antiviral drug.Its structure and anti-HBV mechanism are similar to Bay41-4109.Because of the short half-life of GLS4 JHS,its effect is affected.Ritonavir can inhibit hepatic enzymes to improve the exposure of GLS4 JHS,reduce the dosage and frequency and improve the anti-HBV effect.The antiviral activity and safety of combination of GLS4 JHS and Ritonavir,were evaluated in a randomized double-blind,Entecavir-controlled,sequential panel study.Method:Twenty four HBe Ag-Positive patients with HBV infection were randomized to receive a 28-day course of combination of GLS4 JHS and Ritonavir(120 mg+100mg QD,240mg+100mg QD)or entecavir(0.5mg)in a ratio of 1:1:1.and follow up twelve days.Adverse events,Vital sign,biochemical index,HBs Ag,HBe Ag,HBV DNA titre and other indicators were collected to assess the antiviral activity and safety of the combination of GLS4 JHS and Ritonavir.Result:Twenty four HBe Ag-Positive patients with HBV infection were were randomized and nineteen completed study treatment.Groups were generally well matched.Most adverse events mild Such astransaminase levels elevation,nausea,anemia,WBC reduction,INR prolong,fatigue.Except several participants experienced elevations of ALT during the treatment period and quit the trial.There were no significant clinically relevant changes in vital signs and electrocardiogram parameters.All patients showed a pronounced decline of serum HBV DNA during therapy.Across the GLS4 JHS 120mg group,GLS4 JHS 240mg group and ETV 0.5mg group showed a pronounced suppression of replication of the HBV with a 1.42,2.31 and 3.5 mean log 10 reduction of viral load,respectively.there was statistical significance differences compared with the baseline(p<0.05).But the GLS4 JHS groups experienced viral rebound after last treatment.Quantitative of HBe Ag and HBs Ag declined after 28 days of therapy.Conclusion:The combination of GLS4 JHS and Ritonavir was safe.There is a transient liver dysfunction during the treatment,which needs further study;The combination of GLS4 JHS and Ritonavir produced substantial decrease in HBV-DNA levels in patients chronically infected with HBV,The decrease of HBV-DNA levels are dose dependent.There were decrease in both HBs Ag and HBe Ag levels suggesting the potential of seroconversion.GLS4 JHS should be studied in longer-term dosing trials to be able to evaluate the longterm antiviral effect,to evaluate the rate of seroconversion of HBe Ag and HBs Ag,to evaluate if there is viral rebound after treatment when the HBV DNA suppression,to evaluate if the antiviral efficacy could be Synergy or enhancement when combined with Interferon or Nucleoside analoguese,and to be able to evaluate more definitively its effect on viral replication and ultimately cure of chronic hepatitis B infection.