Mutations in the pol gene of human immunodeficiency virus type 1 in infected patients receiving didanosine and hydroxyurea combination therapy

J Infect Dis. 1997 Oct;176(4):899-903. doi: 10.1086/516511.


The pattern of mutations in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) strains that confer resistance to didanosine (ddI) was analyzed in 2 groups of patients receiving either ddI monotherapy or ddI plus hydroxyurea (HU) combination therapy. Twelve patients receiving combination therapy and 8 receiving monotherapy were tested. Combinations of ddI plus HU did not prevent the onset of mutations, which emerged in 50% of the patients in this group compared with 25% of the ddI monotherapy group. In addition, in 1 patient from the combination therapy arm, who had a limited response to the therapy, an unusual pattern of mutations was found: the insertion of 2 amino acids between residues 69 and 70, a region critical for resistance to nucleoside analogs. The higher efficacy of the combination of HU and ddI compared with that of ddI monotherapy cannot be attributed to a delayed or decreased onset of resistance to ddI.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • DNA, Complementary / analysis
  • Didanosine / therapeutic use
  • Drug Resistance, Microbial / genetics*
  • Drug Therapy, Combination
  • Genes, Viral
  • Genes, pol*
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV-1 / genetics*
  • Humans
  • Hydroxyurea / therapeutic use
  • Mutagenesis, Insertional
  • Nucleic Acid Synthesis Inhibitors / therapeutic use
  • Polymerase Chain Reaction
  • RNA, Viral / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Viremia / diagnosis


  • Anti-HIV Agents
  • DNA, Complementary
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Viral
  • Didanosine
  • Hydroxyurea