New HIV Therapy Clears Out Hidden Virus

Approach might one day lead to a cure, researchers say

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HealthDay Reporter

THURSDAY, Aug. 11, 2005 (HealthDay News) -- In what may prove to be a major breakthrough in the fight against HIV, researchers testing a new approach to treating the disease are inching closer toward a possible cure by eliminating reservoirs of the virus that escape current treatment by hiding in some cells.

Although these findings are preliminary and were obtained using only four patients, the scientists hope that what they have found for the first time is a way of clearing the body of all HIV infection.

"The new approach, in the future, may allow us to make progress in eradication of infection in an HIV-infected person," said lead researcher Dr. David M. Margolis, a professor of medicine and public health at the University of North Carolina.

The report appears in the Aug. 13 issue of The Lancet.

Despite improved outcomes for HIV patients treated with highly active antiretroviral therapy (HAART), which prevents the virus from replicating and restores immune function, the virus remains dormant in some infected CD4 cells. If HAART is stopped, the virus in these cells will start to replicate, causing renewed infection.

The research team knew that an enzyme called histone deacetylase 1 (HDAC1) is needed for HIV to remain in infected cells. In their study, they tested whether valproic acid, which is an inhibitor of HDAC, could purge cells of latent HIV infection.

"Following a relatively brief intervention with intensified therapy with HAART and valproic acid, we showed a significant depletion of resting CD4 cell HIV infections in three out of four patients," Margolis said. "The latent infection of resting CD4 cells is thought to be a major obstacle to eradication of HIV infection."

In their study, Margolis and colleagues treated four HIV patients who were on HAART and whose virus had been suppressed for a long time. For four to six weeks, the patients also were given enfurvitide twice daily. This intensified HAART treatment helped to prevent the further spread of HIV. Then, in addition to HAART, the patients were given oral valproic acid daily for three months.

By the end of the trial, three of the patients had a 75 percent reduction in latent HIV infection, the investigators found. The fourth patient developed anemia during the last four weeks of treatment with valproic acid, so treatment had to be stopped.

Although patients still had reservoirs of latent virus after the trial, this approach may one day lead to a cure for HIV. "The ultimate goal of this new treatment is to clear viral infection," Margolis said. "If this pans out, the goal is to have no replication competent virus left in the body, and so therapy could be stopped."

One expert thinks this new treatment is an important new step forward in HIV therapy.

"Maybe with this drug and maybe with other drugs that may act in these dormant cells, HIV can be removed one day," said Dr. Jean-Pierre Routy, a professor of medicine in the division of hematology at McGill University Health Centre, in Montreal. "That's why I think it's one of the most important publications in a decade."

This finding doesn't mean patients' lives will change in the near future, said Routy, who is the author of an accompanying commentary. "But we can play with what was thought, last week, unplayable. Instead of waiting forever, we can start to think of new therapies. Maybe a cure is conceivable," he said.

In an attempt to replicate these findings, Routy and his colleagues are about to start a trial that will treat 50 HIV patients with this new therapeutic approach.

More information

The U.S. Centers for Disease Control and Prevention can tell you more about HIV/AIDS.

SOURCES: David M. Margolis, M.D., professor, medicine and public health, University of North Carolina at Chapel Hill; Jean-Pierre Routy, M.D., professor, medicine, division of hematology, McGill University Health Centre, Montreal; Aug. 13, 2005 The Lancet

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