Document 0274
 DOCN  M9460274
 TI    Combination therapy with zidovudine and didanosine selects for
       drug-resistant human immunodeficiency virus type 1 strains with unique
       patterns of pol gene mutations.
 DT    9404
 AU    Shafer RW; Kozal MJ; Winters MA; Iversen AK; Katzenstein DA; Ragni MV;
       Meyer WA 3rd; Gupta P; Rasheed S; Coombs R; et al; Stanford University
       Medical Center, CA 94305.
 SO    J Infect Dis. 1994 Apr;169(4):722-9. Unique Identifier : AIDSLINE
       MED/94179879
 AB    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.
 DE    Amino Acids/CHEMISTRY  Base Sequence  Cells, Cultured
       Codon/CHEMISTRY/GENETICS  Didanosine/PHARMACOLOGY/*THERAPEUTIC USE  Drug
       Resistance, Microbial/GENETICS  Drug Therapy, Combination  DNA
       Primers/CHEMISTRY  DNA, Viral/BLOOD/CHEMISTRY  Genes, pol/*DRUG EFFECTS
       Human  HIV Seropositivity/*DRUG THERAPY/MICROBIOLOGY  HIV-1/*DRUG
       EFFECTS/GENETICS  Molecular Sequence Data  Mutation  Polymerase Chain
       Reaction  Proviruses/DRUG EFFECTS/GENETICS  RNA, Viral/BLOOD  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Zidovudine/PHARMACOLOGY/*THERAPEUTIC USE  CLINICAL TRIAL  CLINICAL
       TRIAL, PHASE I  CLINICAL TRIAL, PHASE II  JOURNAL ARTICLE  MULTICENTER
       STUDY  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).