Tenofovir versus tenofovir plus entecavir for chronic hepatitis B with lamivudine resistance and entecavir resistance

Abstract

We compared the viral suppressive efficacy of tenofovir disoproxil fumarate (TDF) mono-rescue therapy (TDF group) and TDF plus entecavir (ETV) combination-rescue therapy (TDF + ETV group) in chronic hepatitis B (CHB) patients with lamivudine resistance and entecavir resistance. One hundred and thirty-three CHB patients with lamivudine and entecavir resistance were investigated. Ninety-six patients were treated with TDF and 37 with TDF + ETV for at least 6 months. We compared the virologic response rate (HBV DNA level <20 IU/mL) between the two groups and identified the predictive factors of treatment outcome. There were no significant differences between the two groups in demographic characteristics. Up to 24 months [median: 18 (range 6-24) months], 85.4% and 89.2% of the TDF group and TDF + ETV group, respectively, achieved a virologic response (P=.068). Only the HBV DNA level at baseline was significantly associated with a virologic response in the multivariate analysis. In a subanalysis of patients with HBV DNA levels ≥4 log (IU/mL) at baseline, a higher proportion of patients in the TDF + ETV group than the TDF group achieved a virologic response (92.9% vs 68.3%; P<.001), while 90% of patients with HBV DNA (IU/mL) levels <4 log in all both TDF and TDF + ETV groups achieved a virologic response. TDF mono-rescue therapy is a reasonable option in patients with lamivudine resistance and entecavir resistance. However, the combination strategy should be considered in patients with high baseline HBV DNA levels.

Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir

“…In our study, the cumulative VR rates in patients with HBV DNA levels ≥ 5.61 log 10 IU/mL (n=19) and those with HBV DNA levels < 5.61 log 10 IU/mL (n=54) were 22.7% and 77.9% at 12 months and 73.2% and 98.2% at 24 months, respectively. This observation is in agreement with two previous studies in CHB patients with resistance to both LAM and ETV [ 21 , 22 ]. Switching to TDF during the early stage of ETV resistance was significantly more effective in suppressing HBV DNA than delayed rescue therapy after HBV DNA increased to higher levels.…”

“…In addition, treatment efficacy of TDF based combination or TDF monotherapy was not statistically different on pre-existing HBV resistant strains or exposure to other antiviral agents (ETV+ADV salvage treatment prior to TDF based rescue therapy). Thus, our studies confirmed that, compared to TDF monotherapy, TDF combination therapy did not provide any additional suppressive effect for CHB patients with resistance to LAM and ETV, which is in consistent with a few results previously reported [ 17 , 21 , 22 ]. However, a systemically designed trial with a large number of patients is needed to evaluate the efficacy of antiviral treatment strategy in CHB patients with multidrug resistance.…”

“…The cumulative rates of VR at 12 and 24 months were 63.3% and 87.1%, respectively. Results in this study were in consistent with previous studies conducted in CHB patients with LAM and ETV resistance [ 17 - 22 ]. Taken together, these data suggest that TDF based rescue therapy is an effective option for CHB patients with treatment failure to LAM and ETV sequential therapy.…”

“…In a recent randomized controlled study, TDF mono-rescue therapy for 48 weeks induced a virologic response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV [ 21 ]. In another study, the TDF group also showed a high virologic response rate comparable to that of the TDF + ETV group, but the duration of followup was relatively short (a median 18 months) [ 22 ]. Therefore, the objective of this study was to investigate the long-term outcomes of TDF based rescue therapy in CHB patients with resistance to both LAM and ETV in routine clinical practice.…”

HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy

“…An even better response rate to TDF + LMV therapy in LMV-resistant patients was reported from a multi-centre study in Korea, where 92.6% of the LMV-resistant patients achieved <20 IU/ml of HBV DNA load after ~3 months of combination therapy8. Another recent study depicted that 85.4% of Korean CHB patients with LMV and ETV resistance achieved virologic response (HBV DNA level <20 IU/mL) following 24 months of TDF mono-rescue therapy21. The salvage potential of TDF was also evaluated in HBV genotype C infected Japanese patients who had failed treatment with other NAs.…”