TY - JOUR
T1 - Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B
T2 - A 5-year randomised study
AU - Fung, Scott
AU - Kwan, Peter
AU - Fabri, Milotka
AU - Horban, Andrzej
AU - Pelemis, Mijomir
AU - Hann, Hie Won
AU - Gurel, Selim
AU - Caruntu, Florin A.
AU - Flaherty, John F.
AU - Massetto, Benedetta
AU - Kim, Kyungpil
AU - Kitrinos, Kathryn M.
AU - Subramanian, G. Mani
AU - McHutchison, John G.
AU - Yee, Leland J.
AU - Elkhashab, Magdy
AU - Berg, Thomas
AU - Sporea, Ioan
AU - Yurdaydin, Cihan
AU - Husa, Petr
AU - Jablkowski, Maciej S.
AU - Gane, Edward
N1 - Funding Information:
This study was funded by Gilead Sciences who also supported the collection and analysis of data.
Publisher Copyright:
© 2016 European Association for the Study of the Liver
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Background & Aims 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). Methods LAM-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. Results Overall, 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 −0.98% and −2.54% at the spine and hip, respectively. Conclusions TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240 weeks. Lay summary The 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.
AB - Background & Aims 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). Methods LAM-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. Results Overall, 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 −0.98% and −2.54% at the spine and hip, respectively. Conclusions TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240 weeks. Lay summary The 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.
KW - Bone mineral density
KW - Emtricitabine
KW - Lamivudine resistant
KW - Renal function
KW - Tenofovir disoproxil fumarate
KW - Viral suppression
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U2 - 10.1016/j.jhep.2016.08.008
DO - 10.1016/j.jhep.2016.08.008
M3 - Article
C2 - 27545497
AN - SCOPUS:85000692609
SN - 0168-8278
VL - 66
SP - 11
EP - 18
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -