Strong antiviral effect of the combination therapy (entecavir and tenofovir) in treatment experienced chronic HBV-mono infected patients with multidrug resistance or only partial responses to previous lines of therapy and advanced liver disease

Treatment of chronic HBV infected individuals with nucleos(t)ide analogs using sequential monotherapy has led to the selection of multiple resistant mutations, endangering patients with advanced liver disease. The aim of this cohort study was to investigate the efficacy and safety of tenofovir (245mg) and entecavir (1mg) in treatment experienced patients with multidrug resistant HBV or only partial responses to previous lines of therapy and advanced liver disease. Methods: Quantitative HBV-DNA measurement with a LLOD <400 copies/ml was used. Resistance und genotyping was done using Innolipa DRV2 and direct sequencing. Results: 12 male patients (9 HBeAg positive) with a median age of 48.5 years were included. At baseline median ALT was 1.6 ULN and HBV-DNA was 5×10⁶ copies/ml. The median treatment duration after initiating the combination therapy was 10 months without significant clinical side effects. The median HBV-DNA level dropped highly significant by 4.6logs (p<0.0001) and 9/12 patients became HBV DNA undetectable. This was accompanied by a significant decline in ALT (p=0.001). Besides previous long-term antiviral treatment (median 55 months), six patients became HBV DNA negative for the first time, demonstrating a high antiviral efficacy of this combination therapy despite pre-existing mutations or only partial responses in earlier therapies. Although viral activity was strongly suppressed in all patients no HBeAg or HBsAg loss was observed. Discussion: The rescue therapy with entecavir and tenofovir in HBV mono-infected patients harbouring complex viral resistance patterns or showing only partial antiviral responses earlier was highly efficient, safe, and well tolerated. More data are certainly needed to judge about the long-term safety, long-term antiviral efficacy using this therapeutical approach.

Entecavir - HBV - Tenofovir