NDLI: Changes in drug sensitivity of human immunodeficiency virus type 1 during therapy with azidothymidine, dideoxycytidine, and dideoxyinosine: an in vitro comparative study.

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Changes in drug sensitivity of human immunodeficiency virus type 1 during therapy with azidothymidine, dideoxycytidine, and dideoxyinosine: an in vitro comparative study.

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Changes in drug sensitivity of human immunodeficiency virus type 1 during therapy with azidothymidine, dideoxycytidine, and dideoxyinosine: an in vitro comparative study.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yarchoan, R. Anderson, B. D. Kojima, E. Shimada, T. O'brien, M. C. Husson, R. N. Mitsuya, H. Shirasaka, T. Broder, S.
Description	Author Affiliation: Shirasaka T ( Experimental Retrovirology Section, National Heart, Lung and Blood Institute, National Cancer Institute, Bethesda, MD 20892.);
Abstract	Human immunodeficiency virus type 1 (HIV-1) strains were isolated from nine patients before and after prolonged therapy with either an alternating regimen of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC) (AZT/ddC) or 2',3'-dideoxyinosine (ddI) alone. All strains obtained from four patients who received AZT/ddC for up to 41 mo were highly insensitive to AZT in vitro. Only one strain obtained after AZT/ddC therapy showed reduced susceptibility to ddC in addition to AZT and had previously unreported amino acid substitutions in the viral polymerase-encoding pol region, whereas three other strains had one or more of the five previously reported AZT-related mutations. In five HIV-1 strains from patients who received ddI for up to 29 mo, no appreciable decrease in sensitivity to ddI was detected. Two strains isolated after ddI therapy had no significant amino acid mutations, although three strains had a mutation reportedly associated with ddI administration. These data suggest that HIV-1 develops reduced susceptibility to AZT more readily than to ddC and ddI and/or that the reduced susceptibility to ddC and ddI is modest in degree. Moreover, the present data suggest that an alternating regimen of AZT and ddC does not block the emergence of AZT-insensitive variants. It should be noted, however, that the current results do not provide a basis for concluding that AZT/ddC or ddI is inferior, equivalent, or superior to AZT as therapy of AIDS.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	2
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Acquired Immunodeficiency Syndrome Drug Therapy Didanosine Pharmacology HIV-1 Drug Effects Zalcitabine Zidovudine Amino Acid Sequence Dose-Response Relationship, Drug Genetic Variation Genetics Isolation & Purification Microbial Sensitivity Tests Molecular Sequence Data Sequence Homology, Amino Acid Comparative Study Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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