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Development of the First AIDS Drugs: AZT and Other Dideoxynueosides

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Human Immunodeficiency Virus Reverse Transcriptase

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Abstract

On March 19, 1987, zidovudine (3′-azido-2′3′dideoxythymidine, azidothymidine, AZT) was approved by the United States Food and Drug Administration (FDA) as the first drug to treat acquired immunodeficiency syndrome (AIDS). The initial development of this drug was the result of a collaboration between scientists in the National Cancer Institute (NCI), Burroughs Wellcome Co., and Duke University. Before this, there was no effective treatment for this devastating disease, and the median survival of AIDS patients was measured in months. Since the development of AZT (Mitsuya et al. 1985; Yarchoan et al. 1986), 25 additional antiretroviral drugs have been approved to treat HIV/AIDS, and combination anti-HIV therapy has converted AIDS from a death sentence to a manageable chronic disease. Several years ago, it was recently estimated that advances in AIDS therapy have already saved over 3 million years of life in the United States alone (Walensky et al. 2006), and we continue to see new benefits from these agents in both the developed world and resource-challenged countries. As a consequence, the use of antiviral drugs to prevent HIV transmission was identified as the “2011 Breakthrough of the Year” by Science magazine (Cohen 2011). Looking back, the rapidity with which the initial AIDS drugs were introduced into the clinic (Table 1.1) (Mitsuya and Broder 1986, 1987; Mitsuya et al. 1985; Yarchoan and Broder 1987a; Yarchoan et al. 1986, 1988, 1989b) and their impact are even more remarkable in light of the skepticism and pessimism surrounding their initial developmental efforts and the fact that we still do not have an effective AIDS vaccine 28 years after the first isolation of the causative agent.

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Conflict of Interest RY, HM, and SB are coinventors on one or more US and/or foreign patents involving dideoxycytidine (zalcitabine), dideoxyadenosine, dideoxyinosine (didanosine), and zidovudine; HM is also coinventor on patents involving darunavir. These inventions were all made as full-time employees of the United States Government under 45 Code of Federal Regulations Part 7. All rights, title, and interest to these patents are assigned to the U.S. Department of Health and Human Services. The government conveys a portion of the royalties it receives to its employee-inventors under the Federal Technology Transfer Act of 1986 (P.L. 99–502).

AcknowledgmentsWe thank Dr. Samuel Broder for his thoughtful review of the manuscript.

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Authors and Affiliations

  1. HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, USA

    Robert Yarchoan & Hiroaki Mitsuya

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  1. Robert Yarchoan
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  2. Hiroaki Mitsuya
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Correspondence to Robert Yarchoan .

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Editors and Affiliations

  1. , HIV Drug Resistance Program, National Cancer Institute, Frederick, 21702, Maryland, USA

    Stuart LeGrice

  2. McGill University, 3775 University Street 3755, Montreal, H3T 1E2, Québec, Canada

    Matthias Gotte

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Yarchoan, R., Mitsuya, H. (2013). Development of the First AIDS Drugs: AZT and Other Dideoxynueosides. In: LeGrice, S., Gotte, M. (eds) Human Immunodeficiency Virus Reverse Transcriptase. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7291-9_1

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