DRUGS HELP BUT HIV HIDES, STUDIES SAY.

Byline: Denise Grady The New York Times

Powerful drug combinations being taken by many people infected with the AIDS virus do not eliminate it from the body, scientists have found. But neither does the virus develop resistance to the drugs in people who follow the strict schedule of medicine.

Three teams, working independently, identified the same set of immune system cells as an important hiding place for the virus, HIV, which becomes dormant but retains the potential to turn active again and infect new cells.

The findings announced Thursday mean that people who benefit from the combination therapy cannot safely discontinue their strict schedule of medications in the foreseeable future, as had been hoped, and, indeed, might need to stick with the costly regimen indefinitely, perhaps as long as they live.

But that could be a long time, the researchers said. The new studies showed that although the virus still lurked in the immune system, it occupied very few cells, and even after two years of therapy had not developed resistance to the drugs.

The combination therapy, including drugs meant to block the virus from making copies of itself, had raised great hopes because in many patients it reduced the human immunodeficiency virus in the bloodstream to levels that could not be detected by standard tests.

The experiments were the first to find the virus hidden in the immune system in patients with undetectable levels of HIV in their blood, and the first to show that the virus did not become drug resistant in people who were responding well to combination therapy.

``This shows that the drugs are really quite good, and are doing what they're supposed to,'' said Dr. David Ho, an author of one of the studies and a researcher at the Aaron Diamond AIDS Research Center in Manhattan, N.Y. ``It should be a motivation for patients to carry on and adhere closely to their regimen.''

Another author, Dr. Joel Gallant, of Johns Hopkins University, said: ``There's a mistaken notion that the drugs have a certain life span and then run out of steam. It's probably the opposite. The longer people remain on the treatment, the longer they continue to do well.''

Scientists not involved in the studies said they were not surprised at the results: They had assumed that the virus must be lying in wait somewhere in the body, because viral levels bounce back up in those who quit taking the drugs. Nonetheless, they said, the studies were valuable. Dr. Jerome Groopman, an AIDS expert at the Harvard Medical School, called the finding that the virus persists ``an important piece of information that would argue strongly that people will need very long-term therapy.''

But Groopman also questioned whether the encouraging data on drug resistance would apply widely to people infected by HIV, because the lack of resistance in the studies did not match the rates that doctors are encountering in practice. He estimated that the drug combinations fail because of drug resistance in as many as 50 percent of patients in some populations.

Dr. Steven Deaks, an AIDS researcher at the University of California, San Francisco, called the studies ``critical milestones.''

``They confirm what we suspected, which is that used appropriately, these drugs probably suppress viral replication to close to zero,'' Deaks said. If the virus is not reproducing, he explained, it cannot mutate, and drug-resistant strains cannot evolve.

``This work confirms our initial hope that these drugs will work for years and years,'' Deaks said. ``It implies that if you do well during the first several months of therapy, you'll do well for the next 50 years.''

Deaks and other researchers also said that combination treatment most often fails in patients who have become drug resistant as a result of previous treatment or because they have not adhered to the dosage schedule needed to prevent the virus from replicating. The new studies, he said, support the observation that in patients who have not taken antiviral drugs before and who take the combination as directed, 80 percent to 90 percent do well.

Two of the studies are being published today in the journal Science. One that included 22 patients was led by Dr. Robert Siliciano at Johns Hopkins University, and the other, with six patients, was directed by Dr. Douglas Richman at the University of California, San Diego. The third, by Dr. Anthony Fauci and his colleagues at the National Institute of Allergy and Infectious Diseases, involved 18 patients and will be published Nov. 25 in The Proceedings of the National Academy of Sciences.

The people studied were taking combinations of three or four drugs meant to block the virus from replicating, or making copies of itself: two inhibitors of the viral enzyme reverse transcriptase, and one or two protease inhibitors, which target a different viral enzyme. All the patients were doing well on the treatment, with blood tests showing undetectable viral loads.