Combination Therapy with Zidovudine and Didanosine Selects for Drug-Resistant Human Immunodeficiency Virus Type 1 Strains with Unique Patterns of pol Gene Mutations

• Published in: The Journal of infectious diseases 1994-04, Vol.169 (4), p.722-729
• Main Authors: Shafer, Robert W., Kozal, Michael J., Winters, Mark A., Iversen, Astrid K. N., Katzenstein, David A., Ragni, Margaret V., Meyer, William A., Gupta, Phalquni, Rasheed, Suraiya, Coombs, Robert, Katzman, Michael, Fiscus, Susan, Merigan, Thomas C.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acids - chemistry; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antivirals; Base Sequence; Biological and medical sciences; Cells, Cultured; Codon - chemistry; Codon - genetics; Codons; Cultured cells; Didanosine - pharmacology; Didanosine - therapeutic use; DNA; DNA Primers - chemistry; DNA, Viral - blood; DNA, Viral - chemistry; Drug resistance; Drug Resistance, Microbial - genetics; Drug Therapy, Combination; Genes, pol - drug effects; Genetic mutation; HIV; HIV 1; HIV Seropositivity - drug therapy; HIV Seropositivity - microbiology; HIV-1 - drug effects; HIV-1 - genetics; human immunodeficiency virus 1; Humans; Major Articles; Medical sciences; Molecular Sequence Data; Mutation; Pharmacology. Drug treatments; Polymerase Chain Reaction; Proviruses - drug effects; Proviruses - genetics; RNA, Viral - blood; Viruses; Zidovudine - pharmacology; Zidovudine - therapeutic use
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/169.4.722

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 antiretroviral therapy. This study examined drug susceptibilities and pol mutations of HIV-1 strains from patients treated for 1 year with zidovudine, didanosine (ddl), 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.