Can AIDS be cured?
The question could only be imagined a few months ago. But participants at an international meeting on AIDS here last week were jolted when some scientists said that continued use for a few years of new drug combinations, which already drive the AIDS virus to undetectable levels in the blood, might eradicate the virus from patients' bodies. Drug treatment could then be stopped forever for such people. A cure.
For now, there is only the hope of such a result. But Dr. David D. Ho and Dr. Martin Markowitz take the hypothesis that a cure is possible seriously enough that they plan to test it at some point by stopping treatment of a very small number of infected individuals at the Aaron Diamond AIDS Research Center in New York City and possibly elsewhere. Definitive proof of a cure probably could not come for years. Failure could come sooner.
News that some scientists are seriously considering the possibility that new drug treatments might not only control, but cure AIDS has caused widespread excitement, and intense controversy.
To critics, merely raising the possibility of curing what has been a generally fatal disease is far too premature and perilous. In doing so, some critics have warned that scientists could create a false sense of security, leading many to drop their guard against unsafe sex and other risky behavior, and negate gains in prevention if people assume that they could be cured if they did become infected. Another fear is that medical science could get a huge black eye if a widely publicized effort to cure AIDS fails.
In speaking of cure, eradication and elimination, proponents are borrowing words from other areas of medicine where they have differing meanings.Continue reading the main story
Surgeons say that an appendectomy cures appendicitis because after its removal there is no chance the appendix can become inflamed again. But cancer cures are measured in terms of five-year disease-free survival, even though patients may die from the same cancer years later.
For bacterial infections, a cure may be declared for those like gonorrhea or pneumococcal pneumonia that permanently disappear after antibiotic treatment. If a patient develops gonorrhea or pneumonia again, it is from a new exposure.
Viral infections are another story. Cures of most viral diseases like influenza occur naturally, a result of the immune system's defenses. Chicken pox is usually considered cured after the last scab disappears from the skin. But the chickenpox virus remains dormant in nerve cells and often causes shingles in infected individuals decades later. What triggers the delayed effect is not known.
Eradication and elimination are words generally used in the public health field to describe the disappearance of a disease from a geographic area. Only one disease, smallpox, has been eradicated from the world. But many other diseases have been eliminated from certain regions, like polio from the Americas.
Now virologists at the meeting are applying the words eradication and elimination to individual patients in whom H.I.V. cannot be detected after combination drug therapy. Yet no one can say the virus has permanently disappeared because H.I.V. still could be hidden somewhere in the body.
The fact that the concept of a cure for AIDS is on the brink of being tested has caught key Federal officials and agencies by surprise.
There is "no cure on the horizon" for AIDS, Dr. Helene D. Gayle, who heads the AIDS program at the Centers for Disease Control and Prevention in Atlanta, wrote in the program for a session devoted to preventing H.I.V.
Asked at a news conference whether she was challenging scientists who believed a cure might be possible, Dr. Gayle said that the Federal agency does not have a definition of "cure" for AIDS. The issue is semantic "when you talk about cure versus the most effective treatment possible," Dr. Gayle said.
C.D.C. is the Federal agency that has been responsible for tracking AIDS cases in the United States since the disease was first recognized in 1981. The agency's main role is prevention, but a cure would have important bearing on its work, such as in the treatment it recommends for health-care workers who get stuck with needles that might contain H.I.V.-contaminated blood.
Throughout the meeting, many participants tried to play down reports of the new combination drug treatments for AIDS and the concept of a cure. One reason was political in-fighting among the various fields in AIDS research. Those in prevention, for example, were concerned that widespread publicity about treatment success could threaten funds for their own work.
As a panelist discussing the future of AIDS therapy, Dr. Stefano Vella of Rome said: "Eradication should be just a challenging research issue."
And Dr. Kevin DeCock, an AIDS expert from London, drew loud applause in his talk summarizing findings from the meeting when he said that "widespread speculation today about cure is a distraction."
The talk of a cure arose for practical and intellectual reasons after investigators were surprised by the results of combination drug therapy and some patients asked how long they would need to continue such treatment.
The combinations often involve taking 15 or more pills a day that must be swallowed according to a rigid schedule that would tax even the most compulsive individual. The timing centers around an empty stomach, and the drugs often cause severe irritation of the stomach. Few believe that many people could adhere to such a regimen indefinitely. Just as important, skipping only a few pills can trigger the emergence of drug-resistant strains of H.I.V. Such a development could create a worse problem than the initial infection because the resistant virus could overwhelm the individual taking the drugs and anyone else to whom the individual transmitted the virus.
In infecting cells, H.I.V. becomes part of a cell's genetic machinery. A cure would mean that if replication of H.I.V. were stopped long enough, all infected cells in the body would eventually die off as they were replaced by newer uninfected ones. How long that process would take to complete, if it were to occur, is not known because scientists do not precisely know the life span of all cells involved in H.I.V. infection.
Thus, Dr. Ho called on mathematicians to calculate the replication rate of H.I.V., the number of infected cells in the body, and the die-off rate to help determine the earliest it might be possible to stop therapy. The current estimate is from one and a half to three years, Dr. Ho said.
Before doctors can stop combination therapy to test the possibility of a cure, they must search lymph nodes for dormant H.I.V. Hidden virus could serve to re-ignite the H.I.V. infection in the body, as embers restart a fire.
"The embers have yet to be defined," Dr. Markowitz said.
Lymph nodes have not yielded H.I.V. in the few investigations scientists have made that have been reported. But because the tests were not undertaken in a formal study, no one knows how often combination therapy eliminates H.I.V. from lymph tissue.
Stopping therapy would be risky because if H.I.V. turns out to be like chicken pox or herpes, infection would come right back and might be impossible to cure.
"We're not there yet," Dr. Ho said. "It's six months from now at the soonest" until the first volunteer stops treatment in the experiment at Aaron Diamond.
It could turn out that H.I.V. is hidden in the brain and is not touched by combination therapy. But Dr. Ho said he did not believe such a development would necessarily pose an insurmountable obstacle to a cure because scientists could then try to develop drugs to reach such areas.
The experiment at the Aaron Diamond center focuses on 12 patients who began taking the combination therapy within 90 days of becoming H.I.V.-infected. Only a small number of H.I.V.-infected people are diagnosed in the earliest stage. But the aim in studying this group is to gain what scientists call "proof of concept."
It may turn out to be easier to cure H.I.V. in the earliest stages of infection, when the immune system is relatively intact, than later after it has been severely damaged by AIDS. The immune system has some capacity to regenerate, but whether it can restore itself to normal after H.I.V. is eliminated is unknown.
Nevertheless, success with early- stage H.I.V. infection would encourage attempts to cure the many people who have been infected for years or who have developed AIDS.
Not even the best news about a cure would necessarily mean much for people in developing countries, where 90 percent of AIDS occurs. Current treatments that are the basis of all the excitement are simply not affordable or available to them. As Dr. Josef Decosas, an international health expert in Montreal, said, "if the cure for AIDS was one clean glass of water, most people in the world today would not have access to treatment."Continue reading the main story