Azidothymidine (AZT)
Although a failure as an anti-cancer drug, AZT has become a front-line defense in managing HIV infections.
Credit: NIH
In the 1950’s and 1960’s, cancer was hypothesized to be caused by retroviruses. When a retrovirus invades a host cell it uses its RNA as a template to create new DNA, which is then incorporated into the host cell’s DNA. In this way, the retrovirus uses the host cell’s DNA to replicate. Azidothymidine, AZT, was synthesized as one of the first retroviral drugs, with the intention of using it to fight cancer. In retrospect, as fewer than 20% of cancers are caused by viruses, it is not surprising that AZT was a complete failure as an anti-cancer drug.
Two decades later, AIDS emerged as a global health crisis. In 1983, scientists in the United States and France identified that AIDS patients were infected by a retrovirus, which was ultimately identified as HIV, the human immunodeficiency virus. In the screening process developed to find promising drugs as rapidly as possible, it quickly became apparent that AZT inhibited the virus without killing the cells. AZT’s effectiveness stemmed from its similarity to the DNA nucleic acid, thymidine. When AZT was present and replaced thymidine, it halted the ability of the retrovirus to incorporate its genetic material into the host cell’s DNA, thus inhibiting the reproduction of HIV.
AZT improves immunity and health in patients with HIV, and initial studies were so effective that it was approved by the Food and Drug Administration for use in HIV-positive patients in a mere 25 months. Because most viruses develop drug resistance over time, AZT is generally given in combination with several other drugs having a variety of modes of action against HIV as part of Highly Active AntiRetroviral Therapy (HAART) protocols. AZT specifically plays a critical role in reducing the risk of an HIV-positive mother giving birth to an HIV positive baby, lowering the risk from a 25 percent chance of transmitting the infection to about 8 percent.
More information is available about AZT at http://pubs.acs.org/cen/coverstory/83/8325/8325AZT.html.
This topic was adapted from the technology milestones project of 2001 ACS President Attila Pavlath.