title: Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy.
abstract: OBJECTIVE
  The aim of the study was to determine whether mutations at RT codon 208 are associated with nucleoside RT inhibitor (NRTI) exposure, NRTI resistance patterns and HIV-1 subtype.
  
  
  METHODS
  Six thousand three hundred and fifty two genotypic resistance tests linked to a clinical database were analysed.
  
  
  RESULTS
  The prevalence of mutations at codon 208 was 6/2347 (0.3%) in treatment-naive and 165/4005 (4.1%) in treatment-experienced persons. H208Y was the most common mutation in both groups (0.2% and 3.8%, respectively) and occurred in 4.5% of treatment-experienced persons with Subtype B, 1.7% of those with Subtype C and 0.7% of those with other non-B subtypes (P=0.001). The association with subtypes was independent of treatment experience. H208Y showed a strong association with NRTI experience, which persisted after adjusting for subtype [odds ratio (OR) 19.34; 95% confidence interval (CI) 7.87-47.54; P=0.0001]. The prevalence of H208Y was highest in genotypes harbouring M184V and the thymidine analogue mutations (TAMs) M41L, D67N, L210W and T215Y. The median number of TAMs was 4 and 0 in genotypes with and without H208Y, respectively (P=0.0001). The prevalence of H208Y declined over time, being highest in 1998 (9.9%) and lowest in 2003 (0.9%) (P=0.0001).
  
  
  CONCLUSIONS
  There is a strong association between H208Y and NRTI experience, particularly in persons with Subtype B harbouring multiple NRTI resistance mutations. These findings indicate an accessory role for H208Y in NRTI resistance.
authors.affiliation: Department of Virology, Royal Free and University College Medical School, Rowland Hill Street, NW3 2PF London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Nebbia
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: D T
authors.initials: DT
authors.lastname: Dunn
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
mesh_terms: D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D020125:Mutation, Missense; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase