Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: a brief history of stavudine (D4T) and its comparison with other dideoxynucleosides.
The occasion of this 25th anniversary issue encouraged us to reminisce about the important history of the discovery of the dideoxynucleoside analogues for the treatment of HIV/AIDS and to chronicle our thoughts about a particular exciting and rewarding period of our scientific careers. Following the identification of the anti-HIV activity of zidovudine (AZT), we participated in the urgent quest to discover optimal treatments of HIV infection and AIDS. A number of previously synthesized nucleoside analogues were comparatively evaluated, and stavudine (D4T) emerged as a promising candidate for development. Following clinical evaluation, D4T became a mainstay of the initial antiretroviral combination therapy, prolonging and saving numerous lives. It has only recently been supplanted by better-tolerated treatments. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010.
Martin
John C
JC
Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, United States. jmartin@gilead.com
Hitchcock
Michael J M
MJ
De Clercq
Erik
E
Prusoff
William H
WH
D015224:Dideoxynucleosides / Q000266:history* / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000266:history* / Q000494:pharmacology* / Q000627:therapeutic use; D018119:Stavudine / Q000266:history* / Q000494:pharmacology* / Q000627:therapeutic use; D014481:United States
D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D054303:HIV Reverse Transcriptase