title: An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs.
abstract: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis.
  
  
  
  We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs.
  
  
  
  Subtype B patients ( n  =   3410) were mostly MSM (78%) and those with subtype C ( n  =   810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P  <   0.001).
  
  
  
  Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated.
authors.affiliation: Public Health Laboratory Birmingham, Public Health England, Heartlands Hospital, Birmingham, UK.
authors.forename: Erasmus
authors.initials: E
authors.lastname: Smit
authors.affiliation: MRC CTU at UCL, University College London, London, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: White
authors.affiliation: Barts and The London NHS Trust, London, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Clark
authors.affiliation: Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Churchill
authors.affiliation: Public Health Laboratory Cambridge, Public Health England, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: HIV i-Base, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Collins
authors.affiliation: Research Department of Infection, Division of Infection and Immunity, University College London, London, UK.|Wellcome Trust Africa Centre for Health and Population Sciences, University of KwaZulu Natal, Mtubatuba, South Africa.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: Research Department of Infection and Population Health London, University College London, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.affiliation: Chelsea and Westminster Hospital, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.affiliation: Research Department of Infection and Population Health London, University College London, London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jose
authors.affiliation: Research Department of Infection and Population Health London, University College London, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Tostevin
authors.affiliation: Research Department of Infection and Population Health London, University College London, London, UK.
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir / Q000008:administration & dosage / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D016049:Didanosine; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D000068698:Tenofovir; D000099227:Abacavir