Development of the first AIDS drugs: AZT and other dideoxynueosides

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.