Inhibition of purified recombinant reverse transcriptase from wild-type and zidovudine-resistant clinical isolates of human immunodeficiency virus type 1 by zidovudine, stavudine, and lamivudine triphosphates.
Cross-resistance between zidovudine, stavudine, and lamivudine was studied, using purified recombinant reverse transcriptase from a zidovudine-susceptible and -resistant pair of clinical isolates of human immunodeficiency virus type 1. The zidovudine-resistant isolate exhibited low-level cross-resistance to both stavudine and lamivudine in drug susceptibility assays. Enzyme from the resistant isolate demonstrated reduced inhibition by zidovudine triphosphate and stavudine triphosphate and, to a lesser extent, lamivudine triphosphate. These findings provide additional evidence at the viral and enzyme level for cross-resistance between zidovudine and stavudine, and they suggest a possible effect of zidovudine resistance on susceptibility to lamivudine.
Duan
C
C
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO 80262, USA. duan_cy@yahoo.com
Poticha
D
D
Stoeckli
T C
TC
Petropoulos
C J
CJ
Whitcomb
J M
JM
McHenry
C S
CS
Kuritzkes
D R
DR
D019380:Anti-HIV Agents / Q000494:pharmacology*; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D054306:Dideoxynucleotides; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D019259:Lamivudine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D018119:Stavudine / Q000494:pharmacology; D013942:Thymine Nucleotides / Q000494:pharmacology; D014162:Transfection; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; C417268:lamivudine triphosphate; D019259:Lamivudine; D015215:Zidovudine; D003570:Cytidine Triphosphate; C052873:zidovudine triphosphate; D018119:Stavudine; D012194:RNA-Directed DNA Polymerase