title: Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase.
abstract: OBJECTIVE
  To identify new drug-resistance-associated mutations in the HIV-1 reverse transcriptase (RT) protein, we screened the RT sequence database of our hospital for alternative amino acid substitutions at known RT drug-resistance positions.
  
  
  METHODS
  The genotypic database used for this analysis contained 1322 RT sequences from 1015 patients. We analysed this RT database with a focus on alternative mutations at RT positions known to be involved in drug resistance. The patterns of drug resistance associated with these alternative mutations were investigated in a separate database containing genotype and drug-susceptibility results.
  
  
  RESULTS
  We identified multiple alternative resistance-associated mutations at amino acid positions 44, 62, 67, 69, 70, 74, 75, 103, 181, 190, 210, and 219 in RT. Phenotypic analysis indicated that drug-resistance properties of the alternative Y181V and L74I mutants are similar, but not identical, to that of the well-known Y181C and L74V mutations.
  
  
  CONCLUSIONS
  This initial survey indicates that many resistance-associated phenomena can be distilled from existing data. These findings endorse a more extensive analysis by computerized methods.
authors.affiliation: Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Nicole Kt
authors.initials: NK
authors.lastname: Back
authors.forename: Anthony
authors.initials: A
authors.lastname: de Ronde
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.forename: Margreet
authors.initials: M
authors.lastname: Bakker
authors.forename: Neil T
authors.initials: NT
authors.lastname: Parkin
authors.forename: Lia
authors.initials: L
authors.lastname: van der Hoek
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D030541:Databases, Genetic; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase