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Cited by 1,163

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Multiple Mutations in HIV-1 Reverse Transcriptase Confer High-Level Resistance to Zidovudine (AZT)

Larder, Brendan A., Kemp, Sharon D.·1989·Science

Abstract

Human immunodeficiency virus (HIV) isolates with reduced sensitivity to zidovudine (3′-azido-3′-deoxythymidine, AZT) from individuals with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were studied to determine the genetic basis of their resistance. Most were sequential isolates obtained at the initiation of and during therapy. Comparative nucleotide sequence analysis of the reverse transcriptase (RT) coding region from five pairs of sensitive and resistant isolates identified three predicted amino acid substitutions common to all the resistant strains (Asp 67 → Asn, Lys 70 → Arg, Thr 215 → Phe or Tyr) plus a fourth in three isolates (Lys 219 → Gln). Partially resistant isolates had combinations of these four changes. An infectious molecular clone constructed with these four mutations in RT yielded highly resistant HIV after transfection of T cells. The reproducible nature of these mutations should make it possible to develop rapid assays to predict zidovudine resistance by performing polymerase chain reaction amplification of nucleic acid from peripheral blood lymphocytes, thereby circumventing current lengthy HIV isolation and sensitivity testing.

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Metadata

Authors
Larder, B. A., & Kemp, S. D.
Venue
Science
Published
1989-12
Volume
246
Issue
4934
Pages
1155-1158
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2046134251
Cited by
1,163
References
29
FWCI
56.55
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Multiple Mutations in HIV-1 Reverse Transcriptase Confer High-Level Resistance to Zidovudine (AZT). https://app.cochat.ai/papers/10.1126/science.2479983
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Larder, B. A., & Kemp, S. D. (1989). Multiple Mutations in HIV-1 Reverse Transcriptase Confer High-Level Resistance to Zidovudine (AZT). Science. https://doi.org/10.1126/science.2479983

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