Virological characteristics of occult hepatitis B virus in a North American cohort of human immunodeficiency virus type 1-positive patients on dual active anti-HBV/HIV therapy

J Clin Virol. 2014 Aug;60(4):347-53. doi: 10.1016/j.jcv.2014.04.021. Epub 2014 May 4.

Abstract

Background: Occult hepatitis B virus infection (OBI) is defined as low-level HBV DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+ patients with OBI may be at risk for HBV reactivation, and often receive dual active anti-HBV/HIV therapy, such as lamivudine (LMV).

Objectives: To determine the presence of OBI in a North American cohort of HIV-1-positive patients.

Study design/methods: 45 HIV-1-positive, serum HBsAg-negative patients, reactive for antibodies to HBV core antigen (anti-HBc), were tested for HBV DNA in plasma and for HBV DNA and covalently closed circular DNA (cccDNA) in PBMC. Ten patients were re-tested after ∼5-10 years, including genotyping and clonal sequence analysis of the HBV polymerase (P) gene and overlapping HBV surface (S) gene from 8 PBMC samples.

Results: Overall, 42% (19/45) tested HBV DNA positive, especially in PBMC (18/45), including 3/18 that were reactive for HBV cccDNA, compared to 17% (8/45) that were HBV DNA reactive in plasma. In 8 patients on LMV, sequence analysis in PBMC showed that all were HBV genotype C or D. Several carried HBV P region variants at residues associated with anti-HBV drug resistance and overlapping S gene region within the major HBsAg "a determinant".

Conclusion: OBI is common in HIV-positive, anti-HBc reactive patients on anti-HBV/HIV therapy, particularly in PBMC. HBV sequence analysis revealed that all had HBV genotype C or D and often had P/overlapping S gene variants possibly associated with dual-active anti-HIV/HBV therapy.

Keywords: Canada; Genotype; HIV; Lamivudine/3TC; Lymphoid cells; Occult HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Asymptomatic Diseases
  • Base Sequence
  • DNA, Viral / blood
  • Female
  • Gene Products, pol / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / genetics
  • Hepatitis B / blood*
  • Hepatitis B / drug therapy*
  • Hepatitis B / virology
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B virus / genetics
  • Humans
  • Lamivudine / therapeutic use
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • North America
  • Sequence Analysis, DNA
  • Viral Load

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Gene Products, pol
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • P protein, Hepatitis B virus
  • Lamivudine