title: Mutations associated with lamivudine-resistance in therapy-naïve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients.
abstract: This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-naïve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-naïve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-naïve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo, Medunsa Campus, Pretoria, South Africa.
authors.forename: S Gloria
authors.initials: SG
authors.lastname: Selabe
authors.forename: Azwidowi
authors.initials: A
authors.lastname: Lukhwareni
authors.forename: Ernest
authors.initials: E
authors.lastname: Song
authors.forename: Yeegan G M
authors.initials: YG
authors.lastname: Leeuw
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Burnett
authors.forename: M Jeffrey
authors.initials: MJ
authors.lastname: Mphahlele
mesh_terms: D020816:Amino Acid Motifs; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013019:South Africa
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase