Emory Report

November 29, 1999

 Volume 52, No. 13

Feinberg delivers Great Teachers Lecture on AIDS research

"I have myself been fortunate to have had great teachers, individuals who inspired in me that pursuing research for the benefit of people is a good thing to do and an honorable thing to do." With this statement, Mark Feinberg opened his Great Teachers Lecture Nov. 18 in Cannon Chapel on "AIDS: Where Did It Come From? Where Is It Going? How Will It End?"

Feinberg joined Emory in 1998 as an associate professor of medicine, microbiology and immunology. He is associate director of the Emory/Atlanta Center for AIDS Research (CFAR).

In 1984 when the cause of AIDS was found to be a retrovirus later named HIV, the medical community had only a few antiviral drugs with which to do battle. These drugs failed. "You had two schools of thought at that point," Feinberg said. "One was from people who, retrospectively, didn't really know what they were talking about but felt that soon we would have drugs available. The other side was overly pessimistic and felt we would never have treatments for this."

The case for pessimism was not unfounded. HIV has a number of essential features that make it deadly, Feinberg said. First, it attacks cells involved in the primary stages of immune response. Once the virus enters the cell, it hijacks cellular machinery, using it to make even more viruses which are released after the cell dies. In effect, HIV strikes behind the lines of the body's defense system, attacking a critical immune control center before the body has time to mount an adequate response.

Second, the critical part of the virus that would be vulnerable to an immune response remains hidden until the final moment of infection. To enter a cell and set up shop, a virus must first be allowed entry into the cell, meaning there must be a positive signal interaction between cell and virus. This need for interaction makes viruses vulnerable to antibodies, but for an HIV infection, the antibody response is inadequate. In the final moments before infection, the viral signal changes shape, revealing the critical part that binds to the cell.

Finally, HIV replicates by a complex process that is extremely error-prone; the virus mutates every time it replicates, changing ever so slightly how it looks to the immune system and to drugs.

"There's a dynamic nature to HIV," Feinberg said. "Basically you're trying to hit a moving target. In the body, it's replicating, and in the course of replicating it's changing. So you have to find a way of stopping this replication because you know the amount of damage this virus is doing is a function of how much it's replicating. And we also know that its ability to develop resistance to drugs is a function of being able to replicate and mutate."

An early drug used against HIV was AZT, but strains of the virus soon mutated and became resistant until doctors began using drugs in combination, a therapy called "cocktails." "There is no drug yet identified that HIV cannot become resistant to when that drug is used in isolation," Feinberg said. "But if you use drugs in combination, you can actually suppress the level of virus replication below the point that we can detect. So the combination therapy has additive or synergistic effects."

However, these positive effects are meaningless for the almost 90 percent of HIV carriers who live in developing countries. Home to about 36 million of the 40 million HIV-positive people on the planet, countries like India and South Africa do not have the economic resources to afford expensive cocktail treatments. And this population of carriers grows by 16,000 daily.

Further, it is in West African countries that we find the true cost of AIDS, a cost that cannot be measured in dollars, Feinberg said. Many of the gains made in past decades to increase life expectancy in African nations have been erased. For many Africans, AIDS is not a disease-it is a force altering family dynamics and reshaping cultures. Even if a cure were found today, the effects of HIV will be felt for generations.

Any possible cure will most likely take the form of a vaccine, Feinberg said. Within the month, he and his colleagues will begin human trials of new vaccines developed by industry. In two years, they hope other vaccines developed at Emory will be ready for clinical trials.

For the immediate future, Feinberg advises people to lower their personal risk through caution and prevention. "There is a question: 'Is everyone in this country at risk for HIV?' The answer to that is yes," he said.

-Paul Thacker

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