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Science 27 September 1991:
Vol. 253. no. 5027, pp. 1557 - 1559
DOI: 10.1126/science.1716788
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Articles

Science, Vol 253, Issue 5027, 1557-1559
Copyright © 1991 by American Association for the Advancement of Science

articles

Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase

MH St Clair, JL Martin, G Tudor-Williams, MC Bach, CL Vavro, DM King, P Kellam, SD Kemp, and BA Larder

Division of Virology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.

Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.


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Didanosine Resistance in HIV-infected Patients Switched from Zidovudine to Didanosine Monotherapy.
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Ann Intern Med 121, 263-268
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