Miami Herald - Thursday, August 22, 1985
Steve Sternberg, Herald Medical Writer

The drugs, HPA-23, suramin and ribavirin, work as a kind of viral birth control, blocking the AIDS virus from multiplying and infecting other cells.

Yet these and other anti-AIDS drugs can't kill the virus, or even repair its havoc in the body's blood-borne defenses, doctors say. The reason: Drugs can't reach the virus.

Eventually, doctors hope, a vaccine now being developed will halt the spread of the epidemic. But that will not help those already afflicted with the disease.

The AIDS virus, HTLV-III, is harbored by the very blood cell it infects. That's why it is so successful, doctors say. The virus injects its genetic malevolence into the heart of a cell, the T-cell, and turns the body's first line of defense into the body's deadliest enemy.

Until AIDS, the now-famous T-cell was virtually unheard of. From AIDS, doctors have learned the T-cell does two things: It matures into a microscopic arsenal of different types of cells that combat infection, and it commands an army of other infection-fighting blood cells.

"Everything is so new," says Dr. Nancy Klimas, an immunologist at the University of Miami. "AIDS is going to teach us more about the immune system than we've ever learned before."

Doctors have learned that the sexually transmitted AIDS virus enters a victim's tissues and is absorbed into the bloodstream, where it attacks the white blood cells. It goes straight for the T-cell, which Klimas calls "the blood's equivalent of a commander-in-chief."

Even then, with the virus firmly rooted in the cell and worming its way into the genetic material, the potential AIDS victim is unaware his blood bears the seeds of disaster.

And the threat builds slowly. Even in AIDS patients, only a few cells are infected, perhaps as few as one in 10,000. Inexorably, the infection spreads.

In the beginning, the victim's T-cells still are working normally. So are other white blood cells, called macrophages, which are scavenger cells ("phage" means to eat) that digest dead blood cells and other waste.

The macrophages are the first cells to spot infections. In healthy people, they alert T-cells that bacteria or viruses have entered the system. The T-cells then mature into helper and suppressor T-cells, which click on and shut off the body's counterattack.

The helper T-cells stimulate B-cells to launch antibodies perfectly tailored to kill organisms they've never encountered before. The suppressor T-cells, always fewer in number, call the attack off.

In AIDS victims, white blood cells never work correctly again. The reason is locked within the nucleus of the helper T-cell, which the AIDS virus prefers. Doctors say they have even located the virus' hiding place.

"We have a highly advanced thumb-printing of the virus," says Dr. Margaret Fischl, the University of Miami's leading AIDS researcher. "We can unravel the DNA and clearly see the virus in the cell's genetic makeup."

The AIDS virus uses the cell's DNA as a sort of a biochemical forge, to hammer out new links in its own genetic chain. It turns the helper T-cell into a tiny virus factory.

"If that cell is stimulated, it divides and produces a daughter cell," Fischl says. "The genetic coding of the virus is forever."

And the deadly cycle of AIDS has begun.

The AIDS virus then infects other helper T-cells, researchers believe. Anything that stimulates the immune system to make more helper T-cells also creates more virus. The infected T-cells no longer can recognize marauding viruses. Still, they stimulate B-cells, which produce antibodies to previous infections -- everything but the AIDS virus.

By this stage, a potential AIDS patient is showing signs of illness. His glands are swollen -- not just in the throat but throughout his body. He is suffering night sweats, fever, chills.

For some unknown reason, only 10 percent to 20 percent of those who show symptoms of infection worsen beyond this stage. The rest are said to have AIDS-related complex, and these symptoms may endure for life.

But they never develop the infections that are the hallmark of AIDS. "When you consider how terrible they look in the laboratory, and they look just awful, it looks for all the world like their immune system is shattered," Klimas said.

"I don't know why some get the infections, and others don't."

Those infections are far more virulent in AIDS victims than they would be even in a transplant patient who is taking immune-suppressant drugs. Kaposi's sarcoma, normally a skin cancer, is found in the liver. Viral infections take root behind the eyes, and parasites -- kept at bay by a normal immune system -- grow in the brain and lungs.

Thus far, doctors spend most of their time treating infections. They are just beginning to treat AIDS itself, Fischl said.

Doctors at UM, the National Institutes of Health and elsewhere will test the anti-viral substances that appear most promising.

HPA-23 is a type of heavy metal used primarily in France, and ribavirin is a drug that has been used to treat the flu. Suramin is newer, and has only been used in a handful of patients.

Unfortunately, Klimas said, early results at NIH and in Europe "have not been hopeful." One reason is that the drugs are toxic and patients may not be able to tolerate lifelong therapy.

Another, she said, is that the virus is extremely clever and "lives in the T-cell, where it's safe."

All three of the drugs attack an enzyme, reverse transcriptase, which the virus needs to reproduce. "Our hope is that the immune system will restore itself once you get rid of the offending agent," Klimas said.

But the pitfalls are formidable, doctors say.

"We still have to figure out the doses and toxicity," Fischl said. "And because viruses can mutate and change, drug resistance will come into play. We now know enough about the virus so that we can realistically approach treatment. Before this, we were trying a little of this, a little of that."

New drugs will have to avoid stimulating the immune system to produce more virus. And, because one-fourth of the body's blood supply always is circulating through the brain, any treatment must safely penetrate into the brain.

An unforeseen danger, Fischl says, is that research into a treatment may move too quickly and may harm AIDS patients rather than help them.

"That's one thing I have been upset about," she says. "A lot of people think we have to do something about treatment now. I think that is the wrong way to approach it. Otherwise we may wind up with a mutated virus."

The virus' ability to change the proteins on its shell is one thing that has slowed vaccine research. Nevertheless, Fischl said, Dr. Luc Montaigne, at the Pasteur Institute in Paris, and Dr. Robert Gallo at NIH may have a prototype ready for testing in about one year.
850822
MH850805

Always watch for outdated information. This article first appeared in 1985. 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, 1985. 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. .