Wall Street Journal - November 14, 1997
Michael Waldholz

Two medical research teams say they uncovered a very tiny amount of dormant HIV, the AIDS virus, in patients whose circulating bloodstream had shown no detectable remnant of the virus for as long as 30 months. The discovery of the "sleeping" virus particles is a significant setback for efforts to cure some patients by treating them with a combination of drugs within weeks of infection.

"It may take a long time, maybe a decade or more of drug treatment, before these [dormant copies of the virus] die off," says Douglas Richman, an AIDS researcher at the University of California, San Diego, who led one of the new experiments. "It means we need to come up with some new strategies if we are going to get rid of the last remnants of the virus. There's a very active discussion as to what, if anything, can be done to destroy these remaining" bits.

Some investigators, led by David Ho of the Aaron Diamond AIDS Research Center, New York, had predicted that it might be possible to eradicate the virus after two to three years of treatment using a combination of three or more drugs, including the powerful protease inhibitors. This cocktail drug therapy has eliminated all detectable evidence of the virus in about 50% to 80% of patients, often restoring health to patients with AIDS and preventing AIDS-related illnesses in people treated soon after exposure.

But Dr. Ho's claim that it may be possible to eradicate the virus-in effect, achieving a cure -- has been hotly debated, and Dr. Ho has come under attack for raising hopes unrealistically. Dr. Ho, whose center contributed to the new studies, says he is undaunted in his efforts to wipe out HIV in some patients. "The new findings are disappointing," Dr. Ho says. "But it also shows us what we need to do next. I'm still hopeful."

In the past two years, treatment of HIV infections has been revolutionized by the new combination drug therapy. For many patients, the therapy has blocked all detectable replication of the virus, driving down virus levels to the point where they are virtually unidentifiable using the most sensitive tests. Patients in some research studies have had their virus levels driven below detection for more than two years, suggesting to some AIDS investigators that it may be possible one day to stop the drug treatment.

But many other scientists say eradication isn't attainable because the virus can embed itself in certain cells that can't be reached by the drugs. In reports by two separate research groups in today's Friday, Nov 14 issue of the journal Science, scientists say that using highly specialized techniques they found evidence of the virus sitting in certain white blood cells that play an important role in the body's disease-fighting immune system.

In one experiment led by Robert Siliciano of Johns Hopkins University, Baltimore, researchers found very low levels of the virus in "quiescent" blood cells. Scientists say that the virus inside the sleeping cells will emerge only if and when the cells are turned on following exposure to certain infectious agents.

Collected together, the total amount of virus uncovered would represent a mere smudge at the bottom of a test tube, Dr. Siliciano says. But if drug therapy was halted and this virus was released, it could replicate itself quickly throughout the immune system, re-establishing HIV infection throughout the body.

"Everyone expected to find a small reservoir of virus hidden somewhere, and now we've found it," Dr. Siliciano says. "As long as these cells remain alive, the virus inside them can someday emerge."

Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases, says the new findings mean that drug therapy can't be stopped even in healthy patients in whom replicating virus is suppressed for two or more years. Dr. Fauci's laboratory reports a similar finding of remnant virus in a separate report in the Proceedings of the National Academy of Sciences.

Still, the AIDS researchers say the new studies provide some good news. The uncovered virus appears to be fully vulnerable to drug therapy. Dr. Ho and other scientists are huddling now to devise a way to stimulate the sleeping cells, forcing them to flush out the virus, which should then be destroyed by the drugs.

Dr. Ho suggests that these cells can be turned on by exposing them to a safe level of an otherwise dangerous toxin, or perhaps by administering to patients certain drugs that stimulate the immune system. But scientists are uncertain whether such action would be safe or whether it would be successful in exposing all the dormant virus to the drugs.

Dr. Ho and others had planned to stop therapy for some long-treated patients, but the new findings mean that such efforts won't be undertaken until the remaining reservoirs of virus can be eliminated.

Until then, scientists say, the therapy, which often involves taking 12 to 20 pills a day, must be continued without fail. In an accompanying article in Science, Simon Wain-Hobson of the Pasteur Institute in Paris says: "We must assume that HIV infection is forever until we know the contrary."

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