Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy

被引:148
作者
Matthews, GV
Bartholomeusz, A
Locarnini, S
Ayres, A
Sasaduesz, J
Seaberg, E
Cooper, DA
Lewin, S
Dore, GJ
Thio, CL
机构
[1] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia
[2] St Vincents Hosp, HIV Immunol Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
[3] Victorian Infect Dis Reference Lab, Melbourne, Vic, Australia
[4] Royal Melbourne Hosp, Victorian Infect Dis Serv, Melbourne, Vic, Australia
[5] Alfred Hosp, Infect Dis Unit, Melbourne, Vic, Australia
[6] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA
[7] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
[8] Johns Hopkins Univ, Dept Med, Baltimore, MD USA
关键词
D O I
10.1097/01.aids.0000218550.85081.59
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Little is known about the prevalence and pattern of hepatitis B virus (HBV) mutations in HIV/HBV co-infected individuals on long-term lamivudine (3TC) therapy. Methods: HBV polymerase/envelope/basal core promoter/pre-core sequences from 81 HIV-HBV co-infected persons who received at least 6 months 3TC were compared to HBV reference sequences. Host and viral characteristics associated with HBV mutations were determined. Results: HBV viraemia was detected in 53 persons (65%) and was associated with lower CD4 cell count nadir and higher HIV RNA at the time of testing but not with 3TC duration. Known 3TC-resistant mutations occurred in 50% and 94% of viremic patients with < 2 years and > 4 years 3TC, respectively. The CD4 cell count at testing was significantly higher in those with 3TC-resistant mutations. The triple polymerase mutant (rtL173V, rtL180M, rtM204V), which behaves as a vaccine escape mutant in vitro, occurred in 17% of viraemic patients. Polymerase mutations that may confer resistance to other anti-HBV agents were also detected. Conclusions: In HIV-HBV co-infected patients, greater immunocompromise is associated with continued HBV viraemia while on 3TC, and development of 3TC-resistant mutations are inevitable with prolonged 3TC use. These Mutant viruses may limit future therapeutic options due to cross-resistance or may produce HBV vaccine escape mutants. Thus, timing and selection of antiretroviral therapy is critical in this population. (C) 2006 Lippincott Williams & Wilkins.
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页码:863 / 870
页数:8
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