Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study

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• 作者：Scott Fung¹ ; ^{scott.fung@uhn.ca} ; Peter Kwan² ; Milotka Fabri³ ; Andrzej Horban⁴ ; Mijomir Pelemis⁵ ; Hie-Won Hann⁶ ; Selim Gurel⁷ ; Florin A. Caruntu⁸ ; John F. Flaherty⁹ ; Benedetta Massetto⁹ ; Kyungpil Kim⁹ ; Kathryn M. Kitrinos⁹ ; G. Mani Subramanian⁹ ; John G. McHutchison⁹ ; Leland J. Yee⁹ ; Magdy Elkhashab¹⁰ ; Thomas Berg¹¹ ; Ioan Sporea¹² ; Cihan Yurdaydin¹³ ; Petr Husa¹⁴ ; Maciej S. Jablkowski¹⁵ ; Edward Gane¹⁶
• 关键词：Tenofovir disoproxil fumarate ; Emtricitabine ; Lamivudine resistant ; Viral suppression ; Bone mineral density ; Renal function
• 刊名：Journal of Hepatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：66
• 期：1
• 页码：11-18
• 全文大小：824 K
• 卷排序：66

文摘

Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB).MethodsLAM-R CHB patients were randomised 1:1 to receive TDF 300 mg or FTC 200 mg and TDF 300 mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA <69 IU/ml (<400 copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data.ResultsOverall, 280 patients were randomised to receive TDF (n = 141) or FTC/TDF (n = 139), and 85.4% completed 240 weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA <69 IU/ml (p = 0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p = 0.41 and p = 0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p = 0.41 and p = 0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was &minus;0.98% and &minus;2.54% at the spine and hip, respectively.ConclusionsTDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240 weeks.Lay summaryThe goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240 weeks.Clinical trial number: NCT00737568.