title: Telbivudine in combination with adefovir versus adefovir monotherapy in HBeAg-positive, lamivudine-resistant chronic hepatitis B.
abstract: OBJECTIVE
  Lamivudine (LAM) resistance is common on lamivudine monotherapy for chronic hepatitis B. This study examined the safety and efficacy of telbivudine (LDT) given with adefovir (ADV) versus ADV monotherapy in patients with chronic, lamivudine-resistant HBV infection.
  
  
  METHODS
  An open-label, 96 week study with planned recruitment of 150 HBeAg-positive, lamivudine-experienced Asian patients with a confirmed YMDD resistance mutation, randomized 1:1 to receive ADV alone or with LDT. The study was terminated early due to difficulty in enrolling monotherapy patients. At termination, 42 patients had received study medication for 8-61 weeks. Due to incomplete enrolment, summary statistics only were prepared, without significance testing.
  
  
  RESULTS
  A total of 42 patients underwent rescue therapy (switch to ADV or LDT + ADV; n = 21 per group). Median treatment duration was 48 weeks in both groups. HBV DNA changes from baseline were greater in the LDT + ADV arm at all time points (Week 48: -7.4 log10 vs. -4.9 log10 copies/ml), and serum DNA was undetectable (<300 copies/mL) at week 48 in 38.5% (5/13) on LDT + ADV versus 0% (0/9) on ADV monotherapy Two patients (9.6%) on ADV monotherapy experienced virologic breakthrough without evidence of ADV resistance, but none on LDT + ADV; and no confirmed ADV resistance was observed in any on-treatment sample. HBeAg loss occurred in three patients on LDT + ADV and one patient on ADV monotherapy through week 48. Safety profiles were similar between the arms.
  
  
  CONCLUSIONS
  LDT + ADV combination treatment showed better outcomes against lamivudine resistant HBV than ADV alone, with a similar safety profile.
authors: Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seoul, South Korea. ahnsh@yuhs.ac.
authors: Sang-Hoon
authors: SH
authors: Ahn
authors: The Kyungpook National University Hospital, Daegu, Korea. yokweon@knu.ac.kr.
authors: Young-Oh
authors: YO
authors: Kweon
authors: Department of Medicine/Gastroenterology, Samsung Medical Centre, Seoul, Korea. sw.paik@samsung.com.
authors: Seung-Woon
authors: SW
authors: Paik
authors: Division of Gastroenterology, Hanyang University Guri Hospital, Gyeonggi-do, Suwon, Korea. sonjh@hanyang.ac.kr.
authors: Joo-Hyun
authors: JH
authors: Sohn
authors: Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. leeks519@yuhs.ac.
authors: Kwan-Sik
authors: KS
authors: Lee
authors: Hallym University Sacred Heart Hospital, Chuncheon, Korea. djkim@hallym.ac.kr.
authors: Dong Joon
authors: DJ
authors: Kim
authors: NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand. teerha.p@psu.ac.th.
authors: Teerha
authors: T
authors: Piratvisuth
authors: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong. mfyuen@hkucc.hku.hk.
authors: Man Fung
authors: MF
authors: Yuen
authors: Phramongkutklao Hospital, Bangkok, Thailand. anuchitwcog2002@hotmail.com.
authors: Anuchit
authors: A
authors: Chutaputti
authors: Tri-Service General Hospital, Taipei, Taiwan, R.O.C. chaoycmd@yahoo.com.tw.
authors: You-Chen
authors: YC
authors: Chao
authors: Novartis Pharma AG, Basel, Switzerland. aldo.trylesinski@novartis.com.
authors: Aldo
authors: A
authors: Trylesinski
authors: Novartis Pharma AG, Basel, Switzerland. claudio.avila@novartis.com.
authors: Claudio
authors: C
authors: Avila