Entecavir plus tenofovir combination therapy in patients with multidrug‐resistant chronic hepatitis B: results of a multicentre, prospective study

• DOI: 10.1111/liv.13059
• Publication Date: 2016-01-19T13:27:08Z
• Authors: Jun Yong Park; Chang Wook Kim; Si Hyun Bae; Kyu Sik Jung; Hee Yeon Kim; Seung Kew Yoon; Kwang‐Hyub Han; Sang Hoon Ahn
• Keywords: Adult; Male; Hepatitis B virus; Guanine; Drug Resistance; 610; Viral/blood; Antiviral Agents; Antiviral Agents/administration & dosage*; Drug Administration Schedule; combination therapy; 03 medical and health sciences; Hepatitis B, Chronic; Drug Therapy; Drug Resistance, Multiple, Viral; Chronic/drug therapy*; 616; Republic of Korea; Guanine/analogs & derivatives*; Humans; chronic hepatitis B; Prospective Studies; Viral/drug effects; Tenofovir; 0303 health sciences; Guanine/administration & dosage; multidrug resistant; DNA; Tenofovir/administration & dosage*; Middle Aged; Hepatitis B virus/genetics; Hepatitis B; tenofovir; 3. Good health; Hepatitis B virus/drug effects; Treatment Outcome; Combination; DNA, Viral; Drug Therapy, Combination; Female; Multiple; entecavir

AbstractBackground & AimsSequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug‐resistant (MDR) CHB patients.MethodsIn this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks.ResultsA total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log10 IU/ml and 2.38 log10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients.ConclusionsIn difficult‐to‐treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.