A two-step approach against Aids involving first flushing the virus out of hiding then killing it with a toxic antibody may offer the first hope for controlling a lifelong Aids infection, US researchers reported yesterday.
The technique to locate and kill dormant HIV-infected immune system cells works in mice and is ready to test in monkeys, the team at the University of California, Los Angeles, said.
It would not offer a cure, but might be a way to help people eventually stop taking the powerful drug cocktails that can keep the virus at bay, but which cause serious side-effects from diarrhea to heart disease.
"Our findings show potential for flushing HIV out of its hiding places in the body," Dr Jerome Zack, an associate director of basic sciences for the UCLA Aids Institute, said in a statement.
Highly active antiretroviral therapy, or HAART, can keep HIV patients healthy for decades, but they do not reach a latent virus - which has been found to lurk inside immune system 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 for first partially activating the cells the virus hides in, then killing the cells before the virus can escape.
The cells they targeted are called resting T-cells. T-cells are the immune system cells that HIV likes best to infect, and these cells can go dormant for long periods of time.
When they are dormant, HIV drugs cannot find them and work against the virus hiding inside.
"About one in a million T-cells holds latent HIV that the antiretroviral drugs can't touch," said Zack. "In order to make it visible, so you can attack it, you have to activate it," he added in a telephone interview.
Attempts to do so have failed in the past because activating all of a patient's T-cells can create potentially deadly illness.
Zack's team used two compounds to only partially activate the T-cells.
One, interleukin-7 or IL-7, is a naturally occurring compound. The other, called prostratin, comes from a tree native to the Pacific island of Samoa.
"They hit a specific activation pathway but don't fully turn on cells," Zack said.
At that point they fire the "guided missile" - an antibody, or targeting immune system compound, spliced to a piece of diphtheria toxin.
"Because the antibody is linked to a toxin molecule, it pops into the cell," Zack said. "The toxin kills the cell before lots of viruses are made."
The approach worked in mice, clearing 70 per cent to 80 percent of the reservoir of latent T-cells, Zack said. It did not mistakenly attack healthy cells - an important finding.
But HIV is difficult to experiment with in animals because it is a virus that affects humans in a unique way. Zack said the next step is to try it in monkeys infected with an engineered human-monkey virus called SHIV.
If tested in people, Zack envisions it would be used along with a HAART cocktail to keep HIV from spreading any further in the body.
Even then, he does not think it would offer a complete cure. HIV is believed to hide in other reservoirs, including certain brain cells. It can reactivate if HAART is stopped - but patients may be able to safely stop HAART for years or even decades.
Aids has killed 28 million people worldwide since the epidemic began in the 1980s, most of them in Africa, where drugs that can fight the disease are a rare luxury.