Mutations in the pol gene of human immunodeficiency virus type 1 in infected patients receiving didanosine and hydroxyurea combination therapy.
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.
De Antoni
A
A
Research Institute for Genetic and Human Therapy, Washington, DC, USA.
Foli
A
A
Lisziewicz
J
J
Lori
F
F
D019380:Anti-HIV Agents / Q000627:therapeutic use; D018076:DNA, Complementary / Q000032:analysis; D016049:Didanosine / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics*; D004359:Drug Therapy, Combination; D005814:Genes, Viral; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016254:Mutagenesis, Insertional; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014766:Viremia / Q000175:diagnosis
D019380:Anti-HIV Agents; D018076:DNA, Complementary; D019384:Nucleic Acid Synthesis Inhibitors; D012367:RNA, Viral; D016049:Didanosine; D006918:Hydroxyurea