Can Interleukin Smoke Out Hidden HIV?

Potent cocktails of anti-HIV drugs have been enormously successful in keeping AIDS at bay in HIV-infected people. But although these "combination" therapies can knock down the virus to undetectable levels, latent HIV lurks in some cells. Now scientists have found that a natural immune system molecule called interleukin-2 (IL-2), if given to patients along with combination therapy, can flush HIV from one major reservoir out into the open. The finding, presented yesterday at the annual meeting of the Infectious Diseases Society of America in Denver, Colorado, raises hopes that it may be possible to one day eliminate the reservoirs and rid people of HIV.

A major HIV reservoir is in T cells--immune cells that are HIV's primary target. When infected T cells are active, they can be attacked by combination therapy; but they also have a quiescent state, during which any HIV they harbor can remain invisible to antiviral drugs for years at a time. IL-2, however, has a potent ability to induce the proliferation, differentiation, and activity of a number of immune cells, including T cells. As a result, a team led by Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, decided to administer IL-2 to patients to see if it would wake up resting T cells and make the HIV they contain vulnerable to attack.

Fauci's team studied a group of 26 HIV-infected patients: 12 received a combination of at least three antiretroviral drugs and 14 received similar combination therapy plus IL-2, given repeatedly but with a minimum of 8 weeks between treatments. At the end of the course of treatments, the team cultured resting T cells from the peripheral blood of the patients; in six of 14 subjects who had received IL-2, the researchers could not detect any HIV capable of replicating. In contrast, the team consistently found live HIV in the T cells from each of the patients on drug therapy alone. They then cultured a much larger sample of resting T cells--up to 330 million cells--from each of the six patients with no detectable live HIV, and could not find any live virus in three of them.

"It's a courageous approach and the results are very intriguing," says immunologist Robert Siliciano of the Johns Hopkins Medical Center in Baltimore, who adds that it's unknown whether this approach clears out all potential reservoirs, including the lymph nodes, brain, and testes. According to Fauci, the "final proof" that IL-2 helps purge HIV reservoirs will come after stopping combination drug therapy and watching what happens. Such trials are planned to begin early next year, he says.

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