Newsday - August 10, 1994
Laurie Garrett. Staff Correspondent

Scientists say the difference for these long-term survivors may be the existence of certain immune-system cells in their bodies, certain genetic characteristics they may share, or even the luck of the draw - meaning they may have been infected with a less powerful strain of the virus that gave their bodies time to mount effective immune responses.

But whatever the difference, many scientists attending yesterday's session of the 10th International Conference on AIDS agreed that these long-term survivors offer the only hope on the horizon that an effective treatment for the disease will be found.

"These people provide guide posts, or targets, for us to aim for in our search for vaccines and therapies," said Dr. David Ho, director of the Aaron Diamond AIDS Research Lab in Manhattan. "These long-term survivors provide . . . a ray of hope, that it is possible to coexist with HIV without harm."

In a speech before the conference yesterday, Ho detailed findings in nine men and one woman who each had lived more than 12 years infected with HIV, never developing symptoms of AIDS-related illnesses. Six of them had no detectable virus left in their blood.

When white blood cells from these long-term HIV survivors were mixed in test tubes with high doses of viruses, there was no discernible activity. But when cells from healthy HIV-negative volunteers were mixed under the same circumstances, they were swiftly overwhelmed and destroyed by rapidly replicating viruses.

When Ho went a step further, removing all so-called CD8 immune-system cells from the long-term survivors' blood samples, he found the viruses quickly overwhelmed remaining cells.

"There is a very dramatic CD8 suppressor effect [on the virus]," Ho said, explaining that the survivors' CD8 cells appear to somehow stop the virus from reproducing. The characteristics of this factor, however, remain a mystery.

Ho said he ruled out unique genetic characteristics, leaving the CD8 cells as the most crucial discernible difference.

Additionally, Ho was able to show that the viruses present in small amounts in the tissues of four of these individuals were "wimpy," meaning they seemed fragile and less virulent. These slower-acting viruses apparently gave the individuals time to build up powerful CD8 responses.

The "wimpy" viruses that remained in their systems, meanwhile, acted like vaccine boosters, constantly restimulating the immune response. Ho found these viruses in the bodies of half of these individuals 12 or 13 years after they were infected, while the other half had eliminated the virus entirely.

Similarly hopeful findings were forthcoming from other researchers who have focused on the rare individuals who survive - or defeat - the AIDS virus.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, estimated that 5 percent of people infected with HIV will live well over a decade without developing AIDS symptoms - in the absence of any type of drug treatment. Microscopic analysis of their surgicallyremoved lymph nodes reveals that, in contrast to what is seen with AIDS patients, they have little or no lymph damage. "This suggests that it is the host response to the virus that is the key," Fauci said.

Dr. Roger Detels of the University of California at Los Angeles said his analysis of 137 long-term U.S. survivors indicates they may have in common certain genetic characteristics that heighten the antiviral response of their immune systems. Dr. Susan Buchbinder of the University of California at San Francisco also found hints of different genetic characteristics involved in the survival of her study group.

Eva Fenyo, of Sweden's Karolinska Institute, said she, like Ho, found no genetic factors. Her studies indicated people may simply benefit from the luck of the draw - if they were infected with a less powerful strain of HIV their bodies had time to mount effective immune responses.

All these findings were music to Jay Levy's ears. For more than 10 years, Levy, of the University of California at San Francisco, has argued that the factors most responsible for determining how long people could survive HIV infection were CD8 cells, and the molecules that they made. As time goes on, Levy's hypothesis gains ever more credibility.

"It takes a long time for people to accept a concept that is new," Levy said. "It's gratifying to see that many people have confirmed what we see."

Now, he said, the race is on to find the mysterious virus-blocking factor produced by CD8 cells. "Instead of making drugs to attack the virus," he said, "let's help the immune system take care of it."
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