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

• Published in: Liver international Vol. 35; no. 10; pp. 2265 - 2274
• Main Authors: Baran, Bulent, Soyer, Ozlem Mutluay, Ormeci, Asli Cifcibasi, Gokturk, Suut, Evirgen, Sami, Akyuz, Filiz, Karaca, Cetin, Demir, Kadir, Besisik, Fatih, Onel, Derya, Gulluoglu, Mine, Badur, Selim, Kaymakoglu, Sabahattin
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.10.2015
• Subjects: adefovir failure; Adolescent; Adult; Aged; Alanine Transaminase; Antiviral Agents - administration & dosage; chronic hepatitis B; DNA, Viral; Drug Resistance, Viral; Female; genotypic resistance; Hepatitis B e Antigens - blood; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Tenofovir - administration & dosage; tenofovir disoproxil fumarate; Treatment Outcome; Viral Load; Young Adult; chronic hepatitis B; genotypic resistance; tenofovir disoproxil fumarate; adefovir failure
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.12831

Background & Aims To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF‐R) and suboptimal response to adefovir (ADF‐S). Methods Nucleos(t)ide analogue (NA)‐naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3‐month intervals in the first year and every 6 months 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. Results A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg+) were included in the study. There were 105 patients in NA‐naïve, 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‐naïve, 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. Conclusion CVR rates during the follow‐up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug‐resistant strains of HBV.