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Some Immune to AIDS, Study Hints : Health: Researchers find cases where blood shows no evidence of infection, although urine is HIV-positive. Others caution that significance of discovery is unclear.

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TIMES MEDICAL WRITER

In a study that lends support to the tantalizing theory that some people are immune to AIDS, a Berkeley microbiologist has discovered a handful of healthy patients whose blood shows no evidence of antibodies to the deadly human immunodeficiency virus, but whose urine is HIV-positive.

None of the seven patients--at least five of whom scientists are certain were exposed to HIV--demonstrate any symptoms of AIDS. And in two cases, urine samples that were positive for HIV later turned negative, leading the researchers to theorize that the patients may have somehow fought off the deadly virus completely.

“We now believe that some individuals may be able to contain, or eliminate the virus from their bodies altogether,” said Dr. Howard Urnovitz, lead author of the study, which will appear Saturday in the Lancet, a British medical journal. “What this tells me is that there is hope in reversing HIV infection if we pay attention on how to do it.”

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Leading AIDS experts were cautious about the study, saying it is important to follow these patients, but that the findings are still just a curiosity.

“At this particular point in time we don’t really know what it means,” said Dr. Anthony Fauci, the government’s top AIDS expert. “Does it mean exposure and infection that is contained? Does it mean exposure but no infection? Does it mean that these people are protected or does it have nothing to do with protection? These are all unanswered questions.”

Gene M. Shearer, an AIDS researcher at the National Cancer Institute who collaborated with Urnovitz on the study, said: “It is puzzling but quite interesting.”

The first patients to exhibit the “blood-negative urine-positive” syndrome turned up during a nationwide clinical trial of a new urine test for AIDS. Other patients emerged when Urnovitz tested 100 people at a clinic for sexually transmitted diseases at San Francisco General Hospital.

The urine test, which has not yet been approved by the Food and Drug Administration, is being developed by Calypte Biomedical, a Berkeley-based company founded by Urnovitz. It may be useful in Third World nations because it is cheaper and less intrusive than blood tests, Urnovitz said.

After additional, more sophisticated testing confirmed the initial results, Urnovitz sent blood and urine samples to Shearer’s laboratory for analysis. Shearer proved that in five of the seven patients, the immune system had been activated against HIV. This meant that they had been exposed to the AIDS virus, although not necessarily infected by it.

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“We can’t say they were infected,” Shearer said. “All we can say is they have had an immunologic experience with some component of the virus.”

Those five people demonstrated a form of immunity known as “cell-mediated immunity.” Unlike “humoral immunity,” in which the body develops antibodies that attack a virus by binding to it, cellular immunity employs so-called killer cells to destroy other cells that the virus has infected.

Shearer and his partner, Dr. Mario Clerici, have long argued that cellular immunity is more important than humoral immunity in keeping the AIDS virus in check. Although theirs is a minority view, other scientists, including polio vaccine pioneer Jonas Salk, have begun to subscribe to it.

In today’s issue of Science, Clerici and Shearer report that they have found a way to boost cellular immunity, and apparently reverse HIV infection, in the test tube by adding a blood protein called interleukin-12.

The cellular-humoral debate is important for researchers who are trying to develop an AIDS vaccine. The fact that five patients in Urnovitz’s study demonstrated cellular immunity suggests that vaccines should focus on boosting cellular immunity, Urnovitz said.

Urnovitz theorizes that the seven patients have developed a “compartmentalized” immune response to HIV, in which antibodies develop in the urogenital tract while the rest of the body wages a cellular immune response that keeps the virus from spreading.

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One patient is a 58-year-old woman whose husband was infected with HIV from a blood transfusion during surgery. Blood tests had repeatedly shown that the woman did not have the virus. But a urine test, taken last year, was positive for HIV.

Then, a more recent urine test was negative. The husband recently died of AIDS, but the woman is healthy. Dr. Daniel Landers, who runs the San Francisco clinic and is a co-author on the Lancet study, said he suspects that the other six patients eventually will show negative urine tests.

He said he believes that in these cases the virus has been “contained and actually eradicated, not allowed to set up and not allowed to take hold. Eventually, we suspect that if you follow these patients over time, we will find no evidence that they were ever exposed.”

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