Journal article

Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine

DJ Tenney, SM Levine, RE Rose, AW Walsh, SP Weinheimer, L Discotto, M Plym, K Pokornowski, CF Yu, P Angus, A Ayres, A Bartholomeusz, W Sievert, G Thompson, N Warner, S Locarnini, RJ Colonno

Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2004

Abstract

Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TC(r)) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (AI463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100..

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