The early burst of activity in support of AIDS research occurred against a backdrop of resentment among advocates for research on other diseases. Many complained that AIDS afflicted far fewer people than their own conditions of interest, yet it received far more research funding.
In recent years, however, such criticism has been muted by the growing applications of AIDS research to other medical areas. Despite the dogged inclination of HIV to elude scientists' best efforts, their work has produced a wealth of knowledge that goes well beyond the scope of AIDS; in particular, it has provided models for fighting other chronic viral infections, historically among the toughest to treat.
As researchers began to better understand how HIV worked, they discovered that the more hits a virus took during different stages of replication, the more effective the result. This led to the development of protease inhibitors and other drugs that could deliver one-two punches at different phases in HIV's cycle.
Scientists are now applying that same approach to other viral diseases. Both hepatitis C and hepatitis B, which together infect an estimated 600 million persons worldwide, are prime candidates. Like HIV, hepatitis C makes a protease enzyme that is necessary for viral replication. And hepatitis B makes an enzyme that is similar to HIV's reverse transcriptase.
"We are learning in hepatitis C treatment, as we learned with HIV, that hitting multiple metabolic pathways of the virus using multiple drugs is effective," says Lawrence Deyton, who directs HIV and hepatitis C programs for the U.S. Department of Veterans Affairs. Moreover, "the knowledge gained in understanding virology and the viral/immune-system interactionseverything we didn't know before HIVwill really help us leapfrog in [hepatitis C research]," Deyton says. "We are just taking all our cards off the HIV table."
The same goes for hepatitis B. Patients who suffer from chronic hepatitis B have a new drug, adefovir dipivoxil, made by Gilead Sciences of Foster City, California. The Food and Drug Administration recently approved the drug to help treat this life-threatening infection. Adefovir was initially tried in AIDS patients but was rejected as too toxic for the kidneys. In lower and safer doses, however, it is effective against hepatitis B.
The other major hepatitis B drug, lamivudine (also known as 3TC and epivir), made by the U.K.-based GlaxoSmithKline, also got its start as an AIDS treatment. In fact, it is still used against HIV in combination with other drugs.
For hepatitis C, the combination of interferon and ribavirinalso originally an HIV drughas produced a better sustained viral response than single-drug therapy.
"Before HIV, many drug companies were scared of researching antiviral drugs," says Vicki L. Sato, president of Vertex Pharmaceuticals in Cambridge, Massachusetts. But lessons learned from HIV "gave us the confidence to try." The company has a protease inhibitor candidate against hepatitis C, called VX-950, which could go into clinical trials sometime next year.
Researchers also are looking to other areas to apply AIDS advances. Among those considered the most promising: blood disorders, autoimmune diseases and cancer. For example, in cervical cancer, non-Hodgkin's lymphoma and Kaposi's sarcoma, both viruses and the immune system are believed to play a role.
Similarly, research into HIV vaccines, however frustrating, may open the door to developing vaccines against other infections. "All sorts of novel strategies are being pursued in HIV vaccine research," says David D. Ho, director of the Aaron Diamond AIDS Research Center in New York City. "If this ultimately results in a protective vaccine, the lessons will be most useful for other vaccines, particularly for malaria and tuberculosis."
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Reprinted from the HHMI Bulletin,
December 2002, pages 12-17.
©2002 Howard Hughes Medical Institute