Stopping the Cycle

In 1985, Dr. Hiroaki Mitsuya of the NIH demonstrated that the drug AZT was able to inhibit the replication of retroviruses, the family of viruses that HIV belongs to, at least in laboratory cultures. Mitsuya believed that AZT could also be effective in human AIDS patients.

AZT represents the first of a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). These drugs control HIV by interfering with the action of proteins essential to the virus's life cycle. Since HIV is a retrovirus, all of its genetic information is stored as a single strand of RNA. In order for HIV to function, it

In April 1984, Secretary of Health and Human Services Margaret Heckler, appearing here with Dr. Robert Gallo, announces the discovery of the virus that causes AIDS.

In April 1984, Secretary of Health and Human Services Margaret Heckler, appearing here with Dr. Robert Gallo, announces the discovery of the virus that causes AIDS.

In the mid-1980s AIDS patients bearing the lesions of Kaposi's sarcoma took hope in AZT, a drug that in laboratory tests inhibited the replication of HIV.

has to convert its RNA into DNA. To accomplish this task, HIV uses chemical compounds, called nucleosides, found inside the cells it infects, as well as a protein called reverse transcriptase.

As part of its life cycle, a healthy cell normally makes DNA from nucleosides, which float freely inside the cell. Upon infection, HIV immediately begins to make the DNA it needs, using the cell's own nucleosides as the building blocks. Reverse transcriptase, using a

New Weapons Against HIV

strand of the virus's RNA as a template, determines the order in which to assemble those nucleosides to form a strand of DNA. When viral DNA is produced, HIV proteins can be made, leading to the production of new HIV particles. The new viral particles bud off the infected T cell and are released into the bloodstream.

Early studies suggested that AZT did indeed benefit HIV-positive patients. The drug interferes with reverse transcriptase's ability to convert viral RNA to DNA. When AZT enters a cell, it is transformed into a chemical compound that closely resembles a nucleoside— closely enough to fool reverse transcriptase. When the protein mistakenly tries to use this false nucleoside, however, DNA synthesis is halted, meaning that viral replication cannot continue. As a result, HIV cannot infect additional cells. According to Dr. Samuel Broder, director of the National Cancer Institute, who tested AZT in laboratory cultures of HIV-infected cells and demonstrated the drug's apparent interference with viral replication, "Attacking the virus by this unique enzyme has given us a foundation stone on which we can build new therapies and combination therapies, hopefully ultimately developing a cure for HIV infection."23

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