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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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

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.[1]

References

  1. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. St Clair, M.H., Martin, J.L., Tudor-Williams, G., Bach, M.C., Vavro, C.L., King, D.M., Kellam, P., Kemp, S.D., Larder, B.A. Science (1991) [Pubmed]
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