No Resistance to Tenofovir Disoproxil Fumarate Detected After up to 144 Weeks of Therapy in Patients Monoinfected With Chronic Hepatitis B Virus Δ

作者：Andrea Snow‐Lampart, Brandi Chappell, Maria Curtis, Yuao Zhu, Florence Myrick, James Schawalder, Kathryn M. Kitrinos, Evguenia S. Svarovskaia, Michael D. Miller, J. Sorbel, Jenny Heathcote, Patrick Marcellin, Katyna Borroto–Esoda · 发表于：Hepatology · 年份：2010 · DOI：10.1002/hep.24078 · 被引用次数：178 · 研究领域：Hepatitis B Virus Studies、HIV/AIDS drug development and treatment、Hepatitis C virus research

UNLABELLED: Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue with potent activity against human immunodeficiency virus type 1 and hepatitis B virus (HBV). To date, no reports of HBV clinical resistance to TDF have been confirmed. In two phase 3 studies (GS-US-174-0102 and GS-US-174-0103), 375 hepatitis B e antigen-negative (HBeAg(-) ) patients and 266 HBeAg(+) patients with chronic hepatitis B (some nucleoside-naive and some lamivudine-experienced) were randomized 2:1 to receive TDF (n = 426) or adefovir dipivoxil (ADV; n = 215) for 48 weeks. After week 48, eligible patients received open-label TDF with no interruption. The studies are being continued through week 384/year 8; week 144 data are presented here. Per protocol, viremic patients (HBV DNA level ≥ 400 copies/mL or 69 IU/mL) had the option of adding emtricitabine (FTC) at or after week 72. Resistance analyses of HBV polymerase/reverse transcriptase (pol/RT) were based on population dideoxy sequencing. Phenotypic analyses were conducted in HepG2 cells with recombinant HBV derived from patient serum. Most patients maintained TDF monotherapy treatment across both studies (607/641, 95%). A resistance analysis of HBV pol/RT was performed at the baseline for all patients, for viremic patients at week 144 or at the last time when they were on TDF monotherapy (34 on TDF and 19 on ADV-TDF), and for patients who remained viremic after the addition of FTC (7/20 on TDF and 5/14 on ADV-TDF). No patient developed amino ...