Identification of a novel hepatitis B virus precore/core deletion mutant in HIV/hepatitis B virus co-infected individuals

• Published in: AIDS (London) Vol. 21; no. 13; pp. 1701 - 1710
• Main Authors: REVILL, Peter A, LITTLEJOHN, Margaret, THIO, Chloe L, LOCARNINI, Stephen A, AYRES, Anna, YUEN, Lilly, COLLEDGE, Danni, BARTHOLOMEUSZ, Angeline, SASADUESZ, Joe, LEWIN, Sharon R, DORE, Gregory J, MATTHEWS, Gail V
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20-08-2007
• Subjects: AIDS/HIV; Antiretroviral Therapy, Highly Active; Antiviral Agents - therapeutic use; Biological and medical sciences; DNA, Viral - blood; DNA, Viral - genetics; Gene Deletion; Genome, Viral; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lamivudine - therapeutic use; Medical sciences; Polymerase Chain Reaction - methods; Prospective Studies; Sequence Analysis, DNA - methods; Viral Core Proteins - genetics; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral hepatitis; Antiretroviral agent; RNA-directed DNA polymerase; Mixed infection; Prevalence; Pathogenesis; precore mutant; Orthohepadnavirus; Hepatic disease; Identification; Epidemiology; Viral hepatitis B; Liver failure; Hepadnaviridae; HIV/hepatitis B virus co-infection; Reverse transcriptase inhibitor; Deletion; Nucleoside analog; Antiviral; Hepatitis B virus; Pyrimidine nucleoside; Human; Immunopathology; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; AIDS; Immune deficiency; immune-escape; Infection; Virus; Polymerase chain reaction; Nucleotidyltransferases; Treatment; Dideoxynucleoside; Viral disease; Digestive diseases; core mutant; Molecular biology
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32826fb305

Although HAART has resulted in improved health outcomes for most HIV-infected individuals, liver failure has emerged as a major cause of morbidity and mortality in people co-infected with hepatitis B virus (HBV). In HBV mono-infected individuals, core deletion mutants are associated with more aggressive liver disease. As HIV accelerates HBV liver disease progression, we hypothesized that HIV-HBV co-infected individuals have increased frequency of core mutations including deletions. To test this hypothesis, we have analysed genome-length sequences of HBV DNA from patients both prior to and during antiviral therapy.
Prospective HIV/HBV co-infected cohort study.
Genomic length HBV DNA was amplified by PCR from the serum samples of ten HIV/HBV co-infected individuals and five HBV mono-infected individuals prior to the commencement of lamivudine therapy and again after nine to 74 months of treatment. The complete genomes were sequenced and in order to further analyse some mutations, their frequency was determined in additional HIV/HBV co-infected and HBV mono-infected individuals.
A novel -1G mutation was identified in the HBV precore and overlapping core genes that truncated the deduced precore/core proteins. The mutant genome was the dominant species in some HIV/HBV co-infected individuals and was more prevalent in HIV/HBV co-infected individuals than HBV mono-infected individuals. The mutation was also associated with high HBV DNA concentrations in HIV/HBV co-infected individuals. Additional mutations were identified in the core/precore and polymerase genes and regulatory regions.
Mutations in the HBV core and precore genes may be contributing to disease pathogenesis in HIV/HBV co-infected individuals.