Beating AIDS will probably require a "two-pronged" approach, says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, one of the federal agencies involved in the research.
First there must be a "direct attack on the AIDS virus itself," says Fauci, "which has to be combined with . . . reconstitution of the immune response."
While no effective treatment yet exists for AIDS, a host of promising new remedies are under investigation and could within the next few years make a major difference for people with the disease.
Treatment, cure and prevention of AIDS all center on fighting the HTLV-3 virus on its own turf -- the immune system's chief defensive player, the white blood cells known as T-cells. HTLV-3 enters the body's T-cells -- like an invader who infiltrates an opponent's weapons plant -- and then produces an enzyme called reverse transcriptase.
Since "reverse transcriptase is a critical element of the initial stage of infection," says Dr. Clifford Lane, assistant clinical director of NIAID, "the area where most of the work has focused is in trying to develop drugs to inhibit the enzyme." By blocking reverse transcriptase, researchers believe they could protect new cells from infection.
"That doesn't necessarily help someone if all their cells are infected," Lane notes, "but just being able to do that would obviously go a long way toward helping people with early stages of the illness."
Experimental drugs that seem to have some inhibiting effect on the enzyme include HPA-23 (under investigation at the Institut Pasteur in France), Suramin (a drug similar to HPA-23 but supposedly with fewer toxic side effects now under study at the National Institutes of Health), and Foscarnet (a Swedish drug being investigated in Europe and at Massachusetts General Hospital in Boston and at NIH).
"Because of the intense interest in AIDS," Lane says, "there are innumerable drugs being developed now." Sometimes these advances happen so quickly that word of them spills out of the traditional scientific channels of communication and into the lay press.
Lane recently learned about one new European-made drug from The Wall Street Journal. The drug, made by Praxis, has not yet been named.
"There were no drugs available that I was aware of which inhibited attachment of the virus to the cell," Lane says. But after reading about this new drug that appeared to do just that, Lane called the European-based company and is now engaged in negotiations to test the drug.
Other promising treatments include:
*Interleukin 2, a protein made naturally in the body by white blood cells, which helps boost the immune system. "There are some very tantalizing pieces of data coming from the studies involving IL-2 ," says NIAID's Lane. "Nothing to indicate that IL-2 by itself will be of value, but we certainly think that it has much hope as a potential combination agent with other drugs ."
*Gamma Interferon, like interleukin 2, a substance normally produced by T-cells. Once the T-cells are infected with HTLV-3, they can no longer send these chemical signals. The theory is to take up the slack by administering these drugs from outside the body. While gamma interferon had "no beneficial clinical effects," reports NIAID's Lane, it did help boost some immune function -- just enough to suggest that "it could play some role in the future as part of a combination drug treatment regimen."
*Ribavirin, a drug that has been somewhat successful in treating respiratory syncytial virus, a deadly disease of children. In the test tube, ribavirin has been able to inhibit the growth of HTLV-3. Whether it will be successful in the body is not yet known.
*Bone marrow transplants. Researchers at the National Institutes of Health are working with three sets of identical twins in which one of the twins has AIDS and the other is healthy. The idea is to transfer uninfected bone marrow from the healthy twin to the twin with AIDS. Because their immune systems are essentially genetically identical, chances are good that the bone marrow won't be rejected by the twin recipient.
*Combination treatments, which might combine several drug treatments, or perhaps a drug with a bone marrow transplant.
"We have evidence that IL-2 may be a good immuno-enhancing agent," explains Lane. "We have evidence that bone marrow transplantation and lymphocytes may be a significant immuno-enhancing agent. We have evidence that Suramin may be an antiviral drug. These are the things that we are now looking toward combining."
Another idea is to create a kind of "super activated" T-cell that could be given to AIDS patients to boost their immune systems. T-cells would be removed from the blood or bone marrow, incubated in a test tube with IL-2 to give them a boost, and then injected into the AIDS patients.
The hitch is that if the T-cells are taken from AIDS patients, the IL-2 could also help promote growth of the HTLV-3 virus that's hidden inside the cell. But if the T-cells are taken from a healthy and immunologically compatible donor -- again, probably a twin -- the procedure might buy some time for the AIDS patient. Later, with modifications, it may be tried on people who are not twins.
One key to future treatment may lie in the theory that "cofactor" diseases play a role in creating the ideal conditions for developing AIDS. In Zaire, where AIDS affects men and women in equal numbers, there is a high incidence of hepatitis, Epstein-Barr virus (the virus that causes mononucleosis) and CMV (or cytomegalovirus) infections among the general population. A similar high incidence of these three infections is also seen, says NIAID's Fauci, among the gay population in the United States. If these cofactor infections are not present, scientists hypothesize, the AIDS virus may not be able to take hold.
Ultimately, however, the quest is for a vaccine that could eradicate AIDS.
"The good news," says NIAID director Fauci, "is that we do have the virus in a highly purified cloned form, so that we can take different segments of the virus and experiment, for example, with an animal and immunize it."
But the bad news, he says, is that researchers are still stumped about just what protects the body against the virus. That knowledge may be a crucial step in obtaining an effective vaccine. Also, HTLV-3 seems able to mutate, or change, just enough to make it more difficult for a vaccine to be effective.
"The question that keeps getting asked," says NIAID's Fauci, "is when are we going to have a vaccine? Not only do we not know when we are going to have a vaccine that's effective, but we don't know if we're going to have a vaccine that's effective because we still do not know what the protective mechanisms against the virus will be."