The day is not too far off when AIDS will be fought with a combination of various drugs, much like practically all cancers are today, says Dr. Robert Yarchoan, the senior investigator at the National Cancer Institute in Bethesda.
"The next couple of years will really be exciting. A number of combination therapies are being tested right now to see if patients do better on them than on just AZT alone," Yarchoan said Wednesday in a talk before 400 health care professionals and people with AIDS in Baltimore.
AZT, or azidothymidine, is the only anti-AIDS drug that has been approved in this country.
Combination therapies are one of the new strategies that are on the horizon for patients in "the increasing epidemic of HIV, a very complicated virus," Yarchoan said.
Human immune deficiency virus, or HIV, is the virus that causes acquired immune deficiency syndrome, which destroys the immune system and paves the way for overwhelming infections and cancers that lead to death.
Yarchoan was a speaker at a two-day conference on AIDS: A Challenge to Primary Care, which ended yesterday.
The conference was sponsored by the University of Maryland Schools of Nursing and Medicine, Maryland AIDS Professional Education Center, Mid-Atlantic AIDS Regional Education and Training Center and the Maryland Health Department's AIDS Administration.
Yarchoan said that within the next year or two, a great deal of basic research that has been going on for the last five years will begin to pay off in new therapies that will help build drug combinations "and this is much like in cancer therapy where there are very few cancers that are treated with one drug now."
In one of the new strategies, antiviral drugs like AZT and DDI, which block the replication of the AIDS virus, will be used in combination with another agent to build up the immune system. It's likely that patients will be immunized with part of the virus or that "we'll use certain chemicals or even something like bone marrow transplantation," Yarchoan said.
"I think one of the questions right now is why, when you give antivirals, don't you see a more complete reconstitution of the immune system and I don't think we really understand that," he said. "Once we get a handle on why that occurs, we may be able to target certain immune-stimulatory therapy."
Yarchoan said that "we will see combinations" of AZT and DDI (dideoxyinosine), and combinations of AZT and DDC (dideoxycytidine), and AZT and interferon.
Like AZT, DDI appears to control the growth of the AIDS virus and enables patients to gain weight, feel better and develop some resistance to infection. At high doses, DDI causes peripheral neuropathy, or pain in the feet. At low doses, the drug is very well tolerated for up to two years, Yarchoan said.
"We cannot conclude that it [DDI] is better than AZT or as good as AZT," he said, "but three comparative trials are under way to look at this."
DDC, another promising AIDS drug, has been under clinical study since 1987. Currently, it is being compared with AZT in patients with AIDS or advanced ARC, a forerunner of full-blown AIDS.
A second study, now under way, is comparing DDI with AZT in patients who have completed one year of treatment with AZT. To date, the only serious side effect with DDI has been peripheral neuropathy in 10 percent of the people who have taken it.
Interferon, one of the first human drugs manufactured through genetic engineering, is an immunity enhancer. Last year, the drug was approved by the Food and Drug Administration for use against Kaposi's sarcoma, one of the cancers that kills AIDS patients.
Yarchoan said that most of the drugs that have been shown to be active against the virus have focused on reverse transcriptase, a key enzyme that enables the genetic material or the virus to replicate itself.
"But, as we start to get therapies targeting other steps in the life cycle of the virus, they'll probably be used eventually in combination with drugs like AZT that work at the reverse transcriptase level," he said.
The tools available now to battle AIDS are inadequate, Yarchoan said. "AZT is not a perfect drug. Even the people on it eventually deteriorate and go on to develop advanced AIDS and die. And others cannot tolerate its toxicities and side effects."
Yarchoan said he is "very excited" about drugs, called protease inhibitors, that block the protease enzyme in the virus. "The inhibitors prevent the protease from making proteins and so the virus can't replicate itself," he explained. "It's sort of like if you take a saw away from a carpenter. Even though he may have big pieces of lumber, he's not going to be able to build a house."