The Wall Street Journal - 04 Aug 1992
Marilyn Chase, Staff Reporter of The Wall Street Journal

Scientists, armed with the latest research from the recent international conference on acquired immune deficiency syndrome, are seeking to uncover the riddles of the human immunodeficiency virus, which invades the body through the bloodstream or sexual contact and cripples the immune system until AIDS develops in the form of opportunistic infections or cancers.

Most scientists initially believed that HIV was straightforward, simply killing the cells it infects. But that doesn't explain why it is difficult to detect HIV in the blood for up to 10 years after infection. During this latent period, individuals are largely free of symptoms, but the body's levels of infection-fighting immune cells dwindle until AIDS develops.

With better tests, Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, and others are trying to establish that lymph nodes filter the virus out of the bloodstream, trapping it in certain lymph cells that normally play a key role in fighting disease. Dr. Fauci believes the cells eventually break down, releasing a "burst of virus" into the blood.

Scientists also are trying to understand why HIV kills more cells than it infects. Some believe in an "innocent bystander" effect, in which uninfected cells get spattered with HIV protein, which provokes other cells to attack. Others believe HIV creates a potent substance called "superantigen" that aggravates these immune cells so they're more vulnerable to HIV infection. A few scientists go a step further, adding that this superantigen may signal the doomed cells to commit mass suicide known as "apoptosis," a term first applied to AIDS by Jean-Claude Ameisen of the Pasteur Institute.

To many researchers, the ultimate frustration is their inability to determine why drugs can't restore immune cells. In advanced AIDS, the immune cell count plunges to 70 or below from the norm of about 1,000. Drugs can boost that count to, perhaps, 150. "But why not back to 700?" asks Samuel Broder, director of the National Cancer Institute. "Is there some damage to the thymus gland, which acts as a drill instructor for immune cells, or to the bone marrow, that renders them beyond repair?" he wonders.

"Is it that our drugs are weak? Is it because drug-resistant mutants of HIV emerge?" he asks. "Or is it that drugs can't reach deep pockets of the virus, located in different compartments of the body?"

This last idea poses a new challenge for drug developers. "The more we learn, the more we know different drugs work on different cellular compartments," Dr. Broder explains. AZT, the most widely used AIDS drug, works best in actively multiplying immune cells, while other drugs are better at reaching dormant ones. Certain brain cells "might act as a sanctuary for the virus," helping it elude the drugs.

Cancer research already has found certain sites of the brain and testicles that appear to deflect the cancer-fighting action of drugs or the immune system, and, therefore, could conceivably harbor cells that sow the seeds of relapse. However, Dr. Broder cautions, applying this to AIDS is so far "just speculation."

Researchers seek to understand why people fall ill with AIDS despite having high levels of infection-fighting antibodies -- the proteins produced by immune cells to fight infection. They wonder if somehow the antibodies alter their behavior and actually enhance infection.

Increasingly, researchers are looking at immune cells known as suppressor cells and killer cells. Jay Levy of the University of California San Francisco says long-term survivors who remain healthy with the virus in their bodies possess high levels of suppressor cells, and he believes such cells produce a substance that holds the virus in check.

In a different line of research, scientists are looking for clues in patients whose immune systems fight back. Gene Shearer of the National Cancer Institute found people who were exposed to HIV yet remained uninfected. While these people made no antibodies against HIV, they did have a robust "cellular immunity," including killer cells. Such findings prompted polio vaccine pioneer Jonas Salk to propose redirecting the goals of vaccine research away from sparking antibodies and more toward mounting a cellular defense.

Adding to the AIDS mystery are recent reports of AIDS-like illness without HIV. Some see these cases as bolstering the view of University of California, Berkeley virologist Peter Duesberg, who argues that HIV alone doesn't cause AIDS. However, the medical establishment remains convinced of HIV's pivotal role in the AIDS epidemic, says Dr. Fauci, citing nearly 250,000 cases in the U.S.

In medical history there have been viruses that guard their secrets to the end, even after doctors find practical solutions. "There are persistent mysteries in every infectious epidemic, for example polio. Most people exposed to polio virus get a harmless gastrointestinal infection and never develop paralysis," says Dr. Broder. "We still don't know why most microbes cause disease."

920804
WJ920801

Copyright © 1992 - The Wall Street Journal. Reproduction of this article (other than one copy for personal reference) must be cleared through the WSJ Permissions Desk.

Always watch for outdated information. This article first appeared in 1992. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1992. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .