The San Francisco Examiner; March 26, 1998
Lisa M. Krieger, Examiner Medical Writer

This natural response, which has protected at least 70 individuals despite hundreds of sexual exposures to HIV, could be induced by a vaccine, said Levy, a professor of medicine at UC-San Francisco and a pioneering AIDS researcher.

"The message is that vaccines should be possible if we can recreate what happens naturally," said Levy. "These people have been immunized to a point that they can resist further and further infection."

Anti-viral drugs such as AZT and protease inhibitors do not prevent infection - and are unlikely to ever eradicate the virus from the body, asserted Levy. Even in people whose viral load is "undetectable," the virus continues to lurk in cells throughout the body.

Scientists must enlist the immune system to help, he said. A synthetic vaccine that contains parts of the AIDS virus could trick the immune system into creating the right kind of response.

Levy's national study of the sex partners of infected people found, remarkably, that some individuals stay uninfected despite repeated episodes of unsafe sex. Some, in bouts of depression, even wished to become infected - but couldn't.

The explanation is thought to lie in the so-called cell-mediated arm of the immune system.

Levy speculates that these infection-free individuals, on first acquaintance with HIV, were exposed to only a tiny amount of the virus. This triggered the protective cell-mediated response - rather than the customary antibody response. Antibodies are notoriously poor at fending off HIV.

Each subsequent exposure acts as a booster shot, ensuring protection against later and larger inoculations of HIV.

The cell-mediated response cranks out a group of white cells called CD-8 lymphocytes, which secrete an antiviral factor called CAF (CD8 antiviral factor) that that prevents HIV from replicating.

In studying patients' blood in the laboratory, Levy found that if he attempted to create an infection in the presence of CD8 cells, viral replication was stopped. However, when the CD8 cells were removed, the virus grew again.

A similar phenomenon may explain "long-term survivors" - people who have been infected with HIV for as long as 20 years, yet remain healthy. These people have become infected but the virus is controlled by a strong CD8 response. Levy is studying 100 of these long-term survivors in San Francisco, thought to represent about 5 to 8 percent of the HIV-infected population.

He is also studying the fascinating case of a pair of identical twins in Zambia. Born to an HIV-infected mother, both had been exposed to HIV. One, perhaps exposed to a lesser amount of virus, has a vigorous cell-mediated response and is uninfected. The other is infected.

"It is an encouraging point for vaccine design - that protection may require a cell-mediated response, as opposed to an antibody response," said Levy. "We need to find a way to get the immune system charged up so it recognizes the virus and keeps it under control."

"These people seem to be naturally immunized," he said.

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