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

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. HBV polymerase/envelope/basal core promoter/pre-core sequences from 81 HIV-HBV co-infected persons who received at least 6 months 3TC were c...

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Published in:	AIDS (London) Vol. 20; no. 6; pp. 863 - 870
Main Authors:	MATTHEWS, Gail V, BARTHOLOMEUSZ, Angeline, LOCARNINI, Stephen, AYRES, Anna, SASADUESZ, Joe, SEABERG, Eric, COOPER, David A, LOWIN, Sharon, DORE, Gregory J, THIO, Chloe L
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 04-04-2006
Subjects:	Adult AIDS/HIV Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral Therapy, Highly Active Antiviral agents Biological and medical sciences CD4 Lymphocyte Count Drug Resistance, Viral - genetics Genes, pol - genetics Hepatitis B - complications Hepatitis B - drug therapy Hepatitis B - virology Hepatitis B virus Hepatitis B virus - drug effects Hepatitis B virus - genetics Hepatitis B virus - isolation & purification HIV Infections - complications HIV Infections - drug therapy HIV Infections - immunology Human immunodeficiency virus Human viral diseases Humans Immune Tolerance Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Lamivudine - therapeutic use Male Medical sciences Middle Aged Mutation Pharmacology. Drug treatments Polymerase Chain Reaction - methods Reverse Transcriptase Inhibitors - therapeutic use Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Envelope Proteins - genetics Viral Load Viremia - virology Immunopathology Antiretroviral agent RNA-directed DNA polymerase Enzyme Transferases Characteristic Enzyme inhibitor Lamivudine AIDS Immune deficiency Infection Resistance Nucleotidyltransferases Treatment Dideoxynucleoside Reverse transcriptase inhibitor Viral disease Nucleoside analog Antiviral Pyrimidine nucleoside
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0269-9370 1473-5571
DOI:	10.1097/01.aids.0000218550.85081.59