Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations

Robert W. Shafer, Michael J. Kozal, Mark A. Winters, Astrid K.N. Iversen, David A. Katzenstein, Margaret V. Ragni, William A. Meyer, Phalquni Gupta, Suraiya Rasheed, Robert Coombs, Michael Katzman, Susan Fiscus, Thomas C. Merigan

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192 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)722-729
Number of pages8
JournalJournal of Infectious Diseases
Volume169
Issue number4
DOIs
StatePublished - Apr 1994

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

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    Shafer, R. W., Kozal, M. J., Winters, M. A., Iversen, A. K. N., Katzenstein, D. A., Ragni, M. V., Meyer, W. A., Gupta, P., Rasheed, S., Coombs, R., Katzman, M., Fiscus, S., & Merigan, T. C. (1994). Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. Journal of Infectious Diseases, 169(4), 722-729. https://doi.org/10.1093/infdis/169.4.722