Scientists Study How HIV Hides in Body

An existing drug used to fight a parasite could prove useful in flushing dormant HIV out of the blood’s macrophage cells, where existing AIDS drugs cannot penetrate, a new study suggests.

Macrophages engulf and digest debris and pathogens in the body, and usually a damaged or infected macrophage would self-destruct. But through multiple steps, HIV turns this part of the immune system into a viral reservoir.

The researchers observed that HIV produces a protein that turns on a cell-survival pathway, which ultimately activates an enzyme called Akt that prevents HIV-infected macrophages from committing suicide. This pathway is also important for certain cancers, and oncologists have been trying to target it for treatments, said Dr. Baek Kim, the study’s senior investigator with the University of Rochester.

With this knowledge, the researchers added Akt-inhibiting drugs to HIV-infected macrophages in lab dishes to see if the cells would die. Both miltefosine, a drug to treat leishmaniasis, and a similar, prospective cancer drug called perifosine quickly killed the infected macrophage cells.

Since miltefosine is already known to be safe in treating leishmaniasis patients, Kim hopes soon to study the drug’s efficacy in targeting macrophages in animals.

“The evidence they show is in fact pretty good,” said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. A subsequent study should test miltefosine in SIV-infected monkeys, Jeang said.

The report, “Akt Inhibitors as an HIV-1 Infected Macrophage-Specific Anti-Viral Therapy,” was published in Retrovirology (2008;5(11):doi:10.1186/1742-4690-5-11).

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