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Aiming low. Antiretroviral therapy knocks HIV below detectable levels (upper line); new therapy aims also to eradicate it form latent reservoirs.

Hitting HIV Where It Hides

One of the most effective defensive tools used by the AIDS virus is its ability to hide out in some of the body's cells. This has prevented even the most powerful drug regimens from completely eradicating HIV in patients. Now, scientists report a strategy that flushes the virus from its hideout, and they claim that it paves the way for a cure.

In 1996, early enthusiasm about the power of new anti-HIV drug cocktails led to a proposition that totally eradicating the virus from the body might take only 2 to 3 years of treatment. But the concept lost currency when it became clear that HIV hides out in reservoirs of "resting" CD4+ white blood cells from which it is very hard to dislodge.

The new study takes an unusually precise approach to dislodging the latent pool. Using evidence that an enzyme called histone deacetylase 1 (HDAC1) plays a crucial role in keeping CD4+ cells in a latent state, virologist David Margolis of the University of North Carolina in Chapel Hill and colleagues gave AIDS patients valproic acid, an HDAC1 inhibitor that's licensed to treat epileptic seizures. Active CD4+ cells evict HIV from its hiding place, and the team administered a new drug, T-20, to help mop up bursts of the virus after the cells spat it out. After 4 months, the amount of infectious HIV in each patient's pool of latent cells declined an average of 75% in three of the four patients studied, the investigators report 13 August in The Lancet.

Researchers roundly praise Margolis for doing this difficult study, but reactions to the data and the postulated mechanism of action have been decidedly mixed. "You have to be very careful about the hope you have for eradication with this," says Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland. Fauci and others earlier had similar success with interleukin-2, but when treatment stopped, HIV quickly surfaced and refilled latent pools within weeks. In addition, the 75% reduction of the latent pool does not impact a patient's health, says Robert Siliciano of the Johns Hopkins University in Baltimore, Maryland.

Margolis stresses that this is just a small "proof of concept" study. "The drumbeat we've been hearing for the last 5 years is this can't be done," says Margolis. "The level of skepticism is very high. And rightly so. But the data we've gotten make me more hopeful."

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