title: Evidence of susceptibility to lamivudine-based HAART and genetic stability of hepatitis B virus (HBV) in HIV co-infected patients: A South African longitudinal HBV whole genome study.
abstract: Reports on the concomitant impact of HIV co-infection and long term highly active anti-retroviral therapy (HAART) on the genetic stability and molecular evolution of HBV are limited in sub-Saharan Africa.
  
  
  
  This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infected patients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infected patients, consecutively recruited and followed-up, were screened for hepatitis B serological markers, and their viral loads determined. The HBV genome was amplified from longitudinal samples and characterized by Bayesian inference, mutational analysis, and identification of immune selection pressure.
  
  
  
  All patients exhibited persistent chronic HBV infection at baseline, as well as over the course of follow-up despite exposure to 3TC-based HAART. The polymerase gene in all isolates was relatively variable prior to HAART initiation at baseline and during the course of follow-up, although primary drug resistance mutations were not detected. All but one patient were infected with HBV subgenotype A1. The divergence rates between baseline and the last follow-up sequences ranged from 0 to 2.0×10(-3) substitutions per site per year (s/s/y). Positive selection pressure was evident within the surface and core genes.
  
  
  
  Despite persistent HBV infection in the HIV co-infected patients exposed to long term 3TC-based HAART, the molecular evolution of HBV over a 5year period was unremarkable. In addition, HBV exhibited minimal genetic variability overtime.
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa.
authors.forename: Edina
authors.initials: E
authors.lastname: Amponsah-Dacosta
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa.
authors.forename: J Nare
authors.initials: JN
authors.lastname: Rakgole
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa.
authors.forename: Maemu P
authors.initials: MP
authors.lastname: Gededzha
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa; National Health Laboratory Service, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.
authors.forename: Azwidowi
authors.initials: A
authors.lastname: Lukhwareni
authors.affiliation: Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Blackard
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa.
authors.forename: Selokela G
authors.initials: SG
authors.lastname: Selabe
authors.affiliation: HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa; South African Medical Research Council, Soutpansberg Road, Pretoria, South Africa. Electronic address: Jeffrey.Mphahlele@mrc.ac.za.
authors.forename: M Jeffrey
authors.initials: MJ
authors.lastname: Mphahlele
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D060085:Coinfection; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D013019:South Africa; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D019259:Lamivudine
keywords: 3TC-based HAART; Genetic variability; HBV; HIV; Molecular evolution; Whole genome