San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Thursday, May 8, 1997 - Page A8
David Perlman, Chronicle Science Editor

However, the success is tempered by the fact that patients will need many years of rigorous treatment to fight the infection -- and even then genes for the virus may lurk indefinitely within some cells.

Those hidden genes, impervious to any known drugs, could later create new particles of HIV and start new rounds of infection, the researchers say.

In three reports published in major scientific journals this week, three teams of international virus hunters describe new knowledge of the course of HIV infection. And they show how older AIDS drugs combined with new protease inhibitors can attack the virus in two successive stages -- the first with remarkable speed, and the next far more slowly.

Ultimately, the researchers say, it may prove possible to eradicate from AIDS patients all the infected cells that can be detected, but unknown reservoirs of cells may remain where even the newest drugs cannot reach.

The reports are being published today in the British journal Nature and tomorrow in the American journal Science. Despite their agreement on prospects for a true cure, the reports each provide evidence that one bastion of cells where HIV has thwarted drug attacks can be successfully breached. Those cells make up the body's network of lymph nodes, including the tonsils. But in a report in Science from a team headed by Dr. Winston Cavert and Dr. Ashley T. Haase of the University of Minnesota, the scientists found that in six months of treatment they could wipe out 99.9 percent of the virus from the scavenging macrophages and CD4 cells in the tonsils of 10 AIDS patients. To do it, they used a powerful drug combination of AZT, 3TC and the protease inhibitor ritonavir.

However, Haase's group found evidence that traces of drug-resistant genetic material from the virus remained in some cells, and he told Science: "There's clearly a residue of virus still stored . . . and if you stop therapy, there's every indication that you can restart the infection."

Calculating the rate at which the drug combination killed so much virus, Haase's group concluded that it might take three years to eliminate all detectable HIV from AIDS patients. But they also warned that lifelong "maintenance therapy" might be needed after a first intensive round of drug treatment.

Two reports in the journal Nature deal with the same problem. In one, a group headed by Dr. Robert F. Siliciano of Johns Hopkins University found that although drug combinations can destroy virtually all the HIV in infected patients, the genetic material capable of producing new virus remains after treatment in a tiny number of "inactive" cells of the immune system.

"These are the cells that are the long-term reservoir of the virus," Siliciano said. "The presumption is that a single infected cell, once activated, can produce enough virus to start the whole thing going again."

The other report in Nature comes from a group headed by Alan S. Perelson of the Los Alamos National Laboratory and Dr. David Ho of the Aaron Diamond AIDS Research Center at the Rockefeller University in New York.

They found that the powerful drug combinations using AZT and 3TC plus the protease inhibitor nelfinavir knocked out 93 to 99 percent of the virus from 14 infected patients within two weeks and that the remaining virus reached undetectable levels in the body much more slowly.

Using the Los Alamos supercomputers, the scientists calculated that it might take two to three years to eliminate all the HIV from the macrophages and lymph nodes in infected patients. And even then, they conceded, virus particles might still lurk in brain tissue or other cells where today's drugs cannot reach them.

Long-term treatment with the drug combinations that include the newly developed protease inhibitors costs thousands of dollars a year; it demands rigid adherence to dosage schedules that are extremely difficult to follow and can often entail severe side effects.

And because none of the teams argues that HIV can yet be eradicated by the new drugs, Ho's team declared: "It would be wrong to conclude we are close to a cure for AIDS. However, the recent advances in treatment . . do warrant a close examination of the feasibility of eradicating HIV from an infected person."
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