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Researchers Discover New Challenge in Curing HIV-AIDS - 2002-05-13


An international team of researchers has uncovered a new obstacle to killing the virus that causes AIDS. Their discovery explains a key reason drugs are not able to cure HIV. It hides in a previously unsuspected place in the body's immune system.

Combinations of powerful drugs, called anti-retrovirals, have suppressed HIV in patients to the point where it is hard to measure. But as researchers like Anthony Fauci of the U.S. National Institute of Allergy and Infectious Diseases have learned, the drugs do not kill the virus. They merely keep virus levels low for as long as they are used. When treatment stops, the virus rebounds.

Dr. Fauci said, "Despite the fact that you do not have detectable viremia [virus in the blood], there is the persistence of a reservoir, a latent reservoir of virus. What it tells you about anti-retroviral research is that the very beneficial drugs that we have available to us now are not succeeding in eliminating the reservoir."

The question researchers have been asking is, where is this reservoir? One part of it was found in 1999 in a set of immune system cells, called T-cells. Now, a U.S.-Greek team, led by physician George Pavlakis at the U.S. National Cancer Institute, has found an overlooked reservoir. It lurks in a different type of immune system cell, called a natural killer cell.

They have the receptors for HIV," Dr. Pavlakis said. "That means HIV can infect this type of cell. HIV can remain in these natural killer cells for long periods of time. So, that makes these cells another hiding place for the virus."

Natural killer cells are a front-line defense against viruses and cancer, a role that HIV infection compromises. Dr. Pavlakis' team reports in the journal, Proceedings of the National Academy of Sciences, that this reservoir is not as large as the T-cell pool, but its smaller size does not necessarily reduce its influence in the course HIV takes.

"Probably, more important than the number of the cells," he said, "is how long they stay infected and how much damage the virus in these cells can do in the body."

So physicians must root out the virus that causes AIDS from yet another location before eradicating it from a patient. This means that treatment regimens may have to be modified. As Dr. Pavlakis notes, what works on T-cells may not work on natural killer cells.

"These cells are substantially different from the T-cells," he continued. "We already have indications that some of the anti-viral drugs may not work as well as we thought before in the natural killer cells, because they are of a different type. So, we may have to think about ways to address the virus that exists in these cells, and to find ways to purge it from these cells."

At the National Institute of Allergy and Infectious Diseases, Anthony Fauci says drug researchers have a big job ahead of them in attacking these cellular bastions of HIV. Dr. Fauci said, "We need to develop drugs that are more potent, because, clearly, the currently available ones are not getting at that reservoir, not getting at the low level of replication of the virus, which continues to replenish this reservoir."

George Pavlakis calls this a demanding order, but one that must be filled. "In order to achieve this important goal," he said, "what we have to do is to chase the virus away from all the hiding places. We cannot ignore any of them."

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