Extensive Polymorphisms Observed in HIV-1 Clade B Protease Gene Using High-Density Oligonucleotide Arrays

Nat Med. 1996 Jul;2(7):753-9. doi: 10.1038/nm0796-753.

Abstract

Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high-density oligonucleotide array sequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV-1 clade B proteases was found to be extremely variable and 47.5% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV-1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Drug Resistance, Microbial / genetics
  • HIV Infections / drug therapy
  • HIV Protease / genetics*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / enzymology*
  • Humans
  • Molecular Sequence Data
  • Oligonucleotides / genetics*
  • Polymorphism, Genetic*

Substances

  • HIV Protease Inhibitors
  • Oligonucleotides
  • HIV Protease