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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.

Type

Journal article

Journal

J Infect Dis

Publication Date

04/1994

Volume

169

Pages

722 - 729

Keywords

Amino Acids, Base Sequence, Cells, Cultured, Codon, DNA Primers, DNA, Viral, Didanosine, Drug Resistance, Microbial, Drug Therapy, Combination, Genes, pol, HIV Seropositivity, HIV-1, Humans, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, Proviruses, RNA, Viral, Zidovudine