Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance

Abstract

It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF+NUC combination therapy. This study recruited 76 antiviral-resistant CHB patients showing CVR on TDF+entecavir (ETV) (n = 52), TDF+lamivudine (LAM; n = 14), and TDF+telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF+NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. The step-down strategy of switching from TDF+NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered.

An observational study on long‐term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate

“…This single-centre, observational study used patients' data from Severance Hospital Liver Disease Cohort Registry (SOLID CORE). 8,10,[22][23][24] Of a total 860 patients who were treated with TDF as an initial therapy for CHB in Severance Hospital, Seoul, Korea from May 2012 to December 2015, 640 consecutive treatmentnaïve patients who met inclusion criteria were analysed.…”

“…6 Therefore, it is recommended as one of the first-line therapies according to international guidelines and it can be used in patients with resistance to other antiviral drugs. 3,4,[7][8][9][10] However, HBsAg loss rate of TDF is very low like other antiviral agents, and most patients may require lifelong therapy. 11 Due to this nature of antiviral therapy, the possibility of nephrotoxicity due to long-term use of TDF has been a concern to many clinicians.…”

Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance

“…(21) In addition, withdrawal of NA in virologically suppressed MDR CHB patients undergoing TDF+NA (most ETV) combination therapy still has sustained anti-viral effects. (22) However, the viral breakthrough in our case occurred after a switch from ETV/TDF combination therapy to TDF monotherapy, indicating a potential risk of viral breakthrough after NA withdrawal. Fortunately, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy, thus suggesting that TDF/ETV combination therapy might be a promising choice for controlling potential TDF-resistant HBV.…”

Long-term Efficacy of Tenofovir Disoproxil Fumarate Monotherapy for Multidrug-Resistant Chronic HBV infection

“…21,22 Our data support the recent concept of switching from combination to monotherapy in patients with antiviral resistance. [23][24][25] The cumulative rate of VR at 48 weeks was 71.7% in the TDF-Mono group and 68.9% in the TDF-Combi group. The VR at week 144 was higher than that in another Korean RCT (91.9% vs 74.5%), likely because of use of different definitions of a VR and differences in the study designs.…”