Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus

Abstract

Background & AimsTo evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S). MethodsNucleos(t)ide analogue (NA)-naive patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA<20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR. ResultsA total of 165 patients (118 men, mean age 4212, 64 HBeAg+) were included in the study. There were 105 patients in NA-naive, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 +/- 14 months. CVR rates in NA-naive, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR=0.56, 95%CI 0.36-0.86, P=0.008), high baseline HBVDNA level (HR=0.64, 95%CI 0.55-0.74, P<0.001) and ADF-R (HR=0.47, 95%CI 0.28-0.81, P=0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments. ConclusionCVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.