A two-step approach againstAIDS involving first flushing the virus out of hiding thenkilling it with a toxic antibody may offer the first hope forcontrolling a lifelong AIDS infection, U.S. researchersreported today.
The technique to locate and kill dormant HIV-infectedimmune system cells works in mice and is ready to test inmonkeys, the team at the University of California, Los Angeles,said.
It would not offer a cure, but might be a way to helppeople eventually stop taking the powerful drug cocktails thatcan keep the virus at bay, but which cause serious side-effectsfrom diarrhea to heart disease.
"Our findings show potential for flushing HIV out of itshiding places in the body," Dr. Jerome Zack, an associatedirector of basic sciences for the UCLA AIDS Institute, said ina statement.
Highly active antiretroviral therapy, or HAART, can keepHIV patients healthy for decades, but they do not reach alatent virus - which has been found to lurk inside immunesystem cells for decades and probably for a lifetime.
Writing in the September issue of the journal Immunity,Zack and colleagues said they had devised a two-step system forfirst partially activating the cells the virus hides in, thenkilling the cells before the virus can escape.
The cells they targeted are called resting T-cells. T-cellsare the immune system cells that HIV likes best to infect, andthese cells can go dormant for long periods of time.
When they are dormant, HIV drugs cannot find them and workagainst the virus hiding inside.
"About one in a million T-cells holds latent HIV that theantiretroviral drugs can't touch," said Zack. "In order to makeit visible, so you can attack it, you have to activate it," headded in a telephone interview.
Attempts to do so have failed in the past becauseactivating all of a patient's T-cells can create potentiallydeadly illness.
Zack's team used two compounds to only partially activatethe T-cells.
One, interleukin-7 or IL-7, is a naturally occurringcompound. The other, called prostratin, comes from a treenative to the Pacific island of Samoa.
"They hit a specific activation pathway but don't fullyturn on cells," Zack said.
At that point they fire the "guided missile" - anantibody, or targeting immune system compound, spliced to apiece of diphtheria toxin.
"Because the antibody is linked to a toxin molecule, itpops into the cell," Zack said. "The toxin kills the cellbefore lots of viruses are made."
The approach worked in mice, clearing 70 percent to 80percent of the reservoir of latent T-cells, Zack said. It didnot mistakenly attack healthy cells - an important finding.
But HIV is difficult to experiment with in animals becauseit is a virus that affects humans in a unique way. Zack saidthe next step is to try it in monkeys infected with anengineered human-monkey virus called SHIV.
If tested in people, Zack envisions it would be used alongwith a HAART cocktail to keep HIV from spreading any further inthe body.
Even then, he does not think it would offer a completecure. HIV is believed to hide in other reservoirs, includingcertain brain cells. It can reactivate if HAART is stopped -but patients may be able to safely stop HAART for years or evendecades.
AIDS has killed 28 million people worldwide since theepidemic began in the 1980s, most of them in Africa, wheredrugs that can fight the disease are a rare luxury.