In the past eight years, scientists have learned more about the AIDS virus than any other infectious agent in history. Yet, despite all the costly national and international research collaboration, the scientific community remains divided about how close it is to controlling the deadly disease.

Some scientists feel the virus has clearly outpaced the capabilities of science; others are optimistic about treatments and future vaccines.

"My own view is that both vaccine and drug development are coming along well. And a lot of progress had been made in prevention," said Dr. Lawrence Kingsley, an AIDS researcher at the University of Pittsburgh.

"It's true that with each thing we learn about the virus, we're taking one step forward. But at the same time we're also taking one step backward," he said.

For instance, research has helped scientists learn that the AIDS virus attacks the body in more ways than they expected. Yet, by learning more about the complexity of the AIDS virus, scientists raise more questions, and the development of treatments and vaccines becomes even more challenging.

Dr. Floyd Naugle, associate director of the University's Ritenour Health Center, said he is not encouraged by medical literature and reports on AIDS developments.

"There has been more attention paid to HIV than any other infectious agent in history," he said. "But despite all that we know about it, it's not terribly encouraging. We've really made little progress at saving lives from AIDS."

To date, 84,985 people have contracted Acquired Immune Deficiency Syndrome, and of those, 48,582 have died. Furthermore, epidemiologists estimate that one to 1.5 million Americans -- and at least five million people worldwide -- are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS.

Kingsley is quick to point out that although science has not yet found a cure for AIDS, it has responded quickly to the disease.

Between 1981, when AIDS was first recognized in young gay men, and 1985, when the first blood test for the AIDS virus became available, scientists made several accomplishments.

High-risk groups and methods of virus transmission were identified, HIV was isolated and shown to cause AIDS, and the virus' targets in the body were described.

"You have to realize that science has never had the opportunity to be up against such a formidable opponent," Kingsley said. "The problems medicine has faced -- syphilis, gonorrhea, other diseases -- haven't been nearly as complex.

"I think the biggest question about AIDS that we face today is how to keep an individual who's infected from progressing," he said. "Furthermore, we want to develop a vaccine for those who aren't infected."

Federal AIDS research funding for the current fiscal year is $2.8 billion, said Delores Spitznagel, spokeswoman for the Office of Management and Budget. AIDS funding for the fiscal year 1985 had been $207 million, she said.

Treatments

Today, more than eight different drugs being clinically tested as AIDS treatments look "reasonably effective," and many other drugs are in early stages of preclinical evaluation, said Robert Yarchoan, a senior investigator in the Clinical Oncology Program of the National Cancer Institute (NCI).

One drug, AZT (azidothymidine or zidovudine), has been used to treat nearly every AIDS patient and has prolonged the lives of many of them, Yarchoan said.

Naugle said AZT, the only antiviral drug approved for widespread use against AIDS by the Food and Drug Administration, had been unsuccessfully used as an experimental treatment for other illnesses and was "just sitting on the shelf."

Yarchoan said scientists working to find AIDS treatments at first experimented with drugs, like AZT, that already existed. In the last few years, however, that approach has changed.

"There has been an evolution of drug development. As we've learned more about different targets of the virus, we've gone from blind tests to specifically designing drugs (to act against HIV)," Yarchoan said.

For several years, scientists have known the virus breaks down the body's immune system by destroying T4 lymphatic cells, or helper lymphocytes, a type of white blood cell that helps fight infection.

When a victim's immune system is destroyed, other diseases called opportunistic infections may take over. It is these diseases that eventually kill the individual.

Just this past year research revealed that in addition to T4 cells, the virus has a second major target: the macrophage, another type of white blood cell.

Scientists believe the virus can hide in small pockets of the macrophage, where the immune system will not see it.

Infected macrophages can also transmit the virus to other macrophages and T cells by binding and fusing with them, and they may be able to carry the virus into the brain, according to a Scientific American report.

This could mean infected macrophages may cause the dementia and neurological problems seen in many AIDS patients, the report said.

The HIV virus most likely enters T cells and macrophages by latching onto a receptor, called CD4, on the surface of these cells. Once this binding occurs, the virus is drawn into the cell and begins to reproduce.

Yarchoan said genetic engineering techniques have enabled scientists to design a synthetic CD4 receptor that diverts the AIDS virus from invading healthy T-cells and macrophages.

Although the drug cannot kill the virus, it hopefully can keep loose viruses in the bloodstream from infecting the immune system, Yarchoan said. Synthetic CD4, which was tested in mice and monkeys, is now being tested on AIDS patients in clinical trials.

Naugle explained that "By using CD4, scientists are hoping they can outfox the virus and keep it from infecting the body's vulnerable cells."

Doris Connolly, program administrator for the AIDS Clinical Trials Unit at the University of Medicine and Dentistry at N.J.(UMDNJ)/Robert Wood Johnson Medical School in New Brunswick, said AIDS treatments fall into two general categories: antiviral drugs and immuno-modulators.

"Antiviral drugs will curtail viral activity. We know they won't kill the virus, but they can keep it quiet," Connolly said. "The other kind of drug --immuno-modulators --stimulates the body's immune system."

Dr. Ronald Nahass, medical director of UMDNJ's AIDS Clinical Trials Unit, said research is beginning to suggest that many antiviral drugs, such as AZT, may also act as immuno-modulators.

"We have no results yet, but it seems that drugs that interfere with the virus generally improve the immune system too -- it seems to be a side benefit of the drugs," Nahass said.

Other drugs given to AIDS patients act not against the virus, but against the opportunistic infections that eventually kill individuals infected with HIV.

For instance, the drug aerosol pentamidine stops the growth of organisms that cause Pneumocystis carinii pneumonia, an opportunistic infection that strikes more than half of all AIDS patients.

Starting this week, this drug is available to AIDS patients through a federal program that allows seriously ill patients access to promising drugs before they are approved for marketing, according to the New York Times.

The AIDS Clinical Trials Program, in which Connolly and Nahass are involved, is run by the National Institute of Allergy and Infectious Diseases (NIAID), the division of the National Institutes of Health that leads in AIDS research.

Through the program, experimental treatments are given to people infected with HIV at 45 hospitals and institutions throughout the country. The recipients of treatments are chosen randomly by computer, Connolly said, and a certain percentage of those chosen receive placebos, or inert substances to serve as an experimental control.

Placebo-controlled experiments allow scientists to accurately determine whether an experimental drug is producing a particular effect or whether results are due to chance or other variables. Neither the investigators nor the recipients know who is receiving the placebo and who is receiving the real drug.

Yarchoan of the NCI said one of the main problems of AIDS treatments is that many, such as AZT, are toxic and cause severe side effects.

"There are certain compounds that work well in the lab, but when they go into clinical-- trials, we find they have a certain toxicity, such as on the kidney," he said. "These drugs may not be the best to use."

Scientists are now especially interested in using several drugs simultaneously in order to reduce toxic effects, Yarchoan said.

For instance, at the AIDS Clinical Trials Unit coordinated by Connolly, physicians are alternating treatments of AZT and ddC, another antiviral drug.

Both AZT and ddC control HIV by slowing its replication. But AZT is toxic, particularly to bone marrow, and ddC is toxic to certain nerves.

Nahass said because their toxicities are different, scientists believe that alternating doses of the drugs may allow body tissues to recover from the toxic effects.

Vaccines

At a press conference in April 1984, representatives of the Department of Health and Human Services and Dr. Robert Gallo, the NCI researcher who, along with a French scientist, discovered the cause of AIDS, reported that a vaccine would be available within two years, Kingsley said.

"But now we're basically still at the beginning stages of asking, 'What are potential vaccines?' " Kingsley said.

Yarchoan, on the other hand, said scientists are more optimistic today about finding an effective vaccine for AIDS. "There was a time two or three years ago when people were very skeptical," he said. "But within the last year, there has been a lot more optimism."

The federal effort to find a vaccine is headed by NIAID and the NCI, but "there's a substantial commitment on the part of the private sector for vaccine development," Kingsley said.

Elaine Baldwin, spokeswoman for NIAID, said the institute is now overseeing phase one testing of two experimental vaccines. Phase one studies -- the first step in testing in humans -- are aimed at discovering any adverse effects and learning about a vaccine's potential.

Normally, when a virus invades the body, chemical markers on its surface -- called antigens -- allow the immune system to recognize the virus and attack it.

A vaccine, which is usually a fragment of the virus' surface or a whole virus that has been killed or weakened, stimulates the immune system to produce antibodies against the virus. The immune system then is, in effect, ready to fight off a future, actual infection of the virus.

According to NCI reports, the problem with developing a vaccine against AIDS is that the virus has several different strains. Because each strain may have different antigens on its surface, the antibodies produced against the vaccine's strain may not protect the body against other strains of the virus.

Scientists have learned the AIDS virus also has the ability to mutate, or change, rapidly. These changes, which are primarily in the outer region of the virus, cause similar complications in vaccine development.

"In the last two years, this variability in the (outer region of the virus) has received a lot of attention," Kingsley said. "With vaccine development, we have to ask questions like 'Do we have to develop multiple vaccines?' and 'How do we measure adequate immunity?' In other words, if I'm negative and am given a vaccine, how do you measure whether the vaccine is effective?"

Kingsley added that candidates for a future vaccine could possibly include people already infected with the virus, in addition to people who are not infected and need to be protected.

"There's a high likelihood that we could vaccinate individuals (who are infected with HIV)," he said. "Their immune response is not sufficient to prevent the disease. But if they're immunized, it's possible to boost their immunity."

Other mysteries

Another focus of future AIDS research is aimed at learning why some people produce antibodies against the virus faster than other people.

At the Fourth International AIDS conference held last summer, Steven Wolinsky of the Northwestern University School of Medicine reported that he found evidence of the AIDS virus in 16 men months before tests detected antibodies against the virus. Wolinsky's study -- the Multi-Center AIDS Cohort Study -- involved a sample of 18 men.

The average interval between infection and the appearance of antibodies was about 18 months, Wolinsky reported, but in one case the period was 42 months.

"We don't know how frequently this occurs, and we don't yet have any answers as to why it occurs," said John P. Phair, chief of infectious diseases at Northwestern and one of the principle investigators of the MACS study.

Kingsley said scientists believe most people infected with the virus develop positive antibody tests within six months.

"One theory is that sexual transmission of the virus introduces only a small amount of the virus into the body," he said. "So there may not be enough virus introduced to stimulate antibody production."

Kingsley added that another important area of research is aimed at learning why so few cells are infected in the body. Many scientists believe the direct killing of T cells does not explain the devastating effects of AIDS, he said.

"A lot of questions have been based on the idea that there must be other explanations for AIDS besides the killing of T-cells," Kingsley said.

Many possibilities, including co-factors such as an already weakened immune system or later additional infections, have been suggested, but none have been proven.

Naugle said that in looking at research, one must remember that the questions being raised are not purely scientific, but deal also with financial, political and social aspects.

"For instance, what if you can keep a person who is infected with the virus alive (through treatment) for the rest of his or her life?" Naugle said. "They would still be infectious, so we'd have to ask about modifying their behavior," he said. "If we didn't, we'd be creating a tremendous burden for society."

Many researchers, he said, agree that the most effective approach to combating AIDS has been and will continue to be education and prevention.

"That's the best answer for the AIDS problem," he said.