title: Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations.
abstract: Drug resistance conferred by specific human immunodeficiency virus type 1 (HIV-1) pol gene mutations has been associated with clinical progression in HIV-infected patients receiving anti-retroviral therapy. This study examined drug susceptibilities and pol mutations of HIV-1 strains from patients treated for 1 year with zidovudine, didanosine (ddI), or zidovudine and ddI. Ten (42%) of 24 patients receiving combination therapy versus 8/26 (31%) receiving only zidovudine had HIV-1 strains with phenotypic zidovudine resistance or a zidovudine resistance pol mutation at codon 215 (P = .6). In contrast, a ddI resistance mutation at codon 74 was less common among patients receiving combination therapy (2/24) than among those receiving ddI only (17/26; P < .001). Two patients receiving combination therapy developed resistance to zidovudine and ddI; they had HIV strains with amino acid mutations at codons 62, 75, 77, 116, and 151. Combination therapy with zidovudine and ddI selects for zidovudine-resistant HIV-1 strains lacking a ddI resistance mutation and for multidrug-resistant strains containing novel pol mutations.
authors.affiliation: Stanford University Medical Center, CA 94305.
authors.forename: R W
authors.initials: RW
authors.lastname: Shafer
authors.forename: M J
authors.initials: MJ
authors.lastname: Kozal
authors.forename: M A
authors.initials: MA
authors.lastname: Winters
authors.forename: A K
authors.initials: AK
authors.lastname: Iversen
authors.forename: D A
authors.initials: DA
authors.lastname: Katzenstein
authors.forename: M V
authors.initials: MV
authors.lastname: Ragni
authors.forename: W A
authors.initials: WA
authors.lastname: Meyer
authors.forename: P
authors.initials: P
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Rasheed
authors.forename: R
authors.initials: R
authors.lastname: Coombs
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001483:Base Sequence; D002478:Cells, Cultured; D003062:Codon / Q000737:chemistry / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D015751:Genes, pol / Q000187:drug effects*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000187:drug effects / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D003062:Codon; D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral; D015215:Zidovudine; D016049:Didanosine