Hemophiliacs Reluctant to Join Study : Attitude of ‘Denial’ Perils Major AIDS Drug Project
The first major nationwide study of an AIDS drug on hemophiliacs infected with the AIDS virus is imperiled because of an unusual and pervasive resistance to participation on the part of hemophiliacs across the country, according to federal health officials and other researchers.
“I think the hemophiliac population is having a difficult time coping with the reality of what is going on here,” said Dr. Daniel Hoth, director of the AIDS program for the federal government’s National Institute of Allergy and Infectious Diseases, one of the study’s sponsors.
“A very large fraction of the hemophiliac community is infected, and this trial offers them the best possible hope of avoiding the consequences of (AIDS) infection,” he added. “But most patients are saying: ‘Being in a clinical trial will remind me that I’m infected--so if I’m not involved, I don’t have to think about it.’ ”
This “denial” among hemophiliacs is unique and unlike that of any other groups affected by the epidemic--it is an attitude that relates to the very nature of hemophilia itself, medical experts say.
Hemophilia is a hereditary clotting disorder, primarily afflicting men but transmitted by women, that is characterized by excessive, sometimes spontaneous bleeding. Hemophilia and related clotting disorders afflict an estimated 20,000 persons in this country. Before 1970, most hemophiliacs were literally bleeding to death, and at very young ages. In 1971, the median age of a person with hemophilia was 11.5 years.
In recent years, however, hemophiliacs have become independent of the health care system and have been able to lead relatively normal lives, despite their serious and chronic condition, largely because of the development in the early 1970s of clotting factor, a concentrated substance pooled from the blood plasma of thousands of donors. Hemophiliacs could store it in the refrigerator and, in the event of a bleeding episode, could infuse themselves at home. By 1981, the median age of a hemophiliac had nearly doubled.
But ironically, the very product that had liberated hemophiliacs from the hospital emergency room and saved them from an almost certain early death had also silently infected many of them by 1982 with the AIDS virus. The disease leaves the body powerless against certain cancers and otherwise rare infections and can invade the central nervous system, causing severe neurological disorders.
Clotting factor products are now treated with heat, a process that easily kills the human immunodeficiency virus. However, although hemophiliacs comprise only a small percentage of AIDS cases in this country--about 800 of more than 80,000 cases--it has been estimated that as many as 90% of those with severe hemophilia already have been infected and are likely to become ill.
“Unfortunately, many assume they will somehow be able to overcome this, even when symptoms begin,” said Dr. Peter Levine, a hemophilia specialist at Worcester Memorial Hospital and director of the New England Regional Hemophilia Program. “In the past, their grasp of reality included a whole series of positive interventions that led to positive outcomes--now they are faced with a reality for which there may not be a positive outcome.”
Placebo Study
Now, by becoming part of a placebo-controlled study that will require them to take pills six times around the clock, they are being asked “to remind themselves constantly that a dagger is hanging over their heads,” Levine said. “You don’t want to confront yourself every four hours with the fact that you are infected with a potentially fatal virus.”
The study is one of two nationwide trials of AZT, the only licensed AIDS drug, on infected individuals who have not yet developed symptoms of the disease. AZT, also known as zidovudine, has been shown to prolong the lives of some patients with fully developed AIDS, but it is not known whether it can prevent or delay the onset of the disease. Also, it can have toxic side effects and researchers are anxious to learn if it can be used both early--during infection--as well as later, after AIDS has developed and when the drug is already known to be valuable.
The hemophilia study was designed to monitor 538 individuals over a four-year period--half will be given AZT, and the other half--the “control” group--will receive a medically worthless placebo, with neither the patients nor the physicians knowing who is receiving what. If there is clear evidence that AZT is having a positive impact, however, the study will be halted and all participants given the opportunity to take the drug.
The second study, also a double-blind, placebo-controlled trial, involves 3,200 nonhemophiliac individuals, many of them infected gay men.
“From a national perspective, both studies are very important,” Hoth said. “Each addresses a different population. One is going well--in part, because there is no denial in the gay community, at least on a mass scale--and one is not.”
‘Piggyback’ Study
Dr. Thomas C. Merigan, author of the hemophilia study, as well as a “piggyback” study that hopes to examine AIDS infection rates among the wives of hemophiliacs, said that he and other scientists conducting the trial are frustrated because they have only enrolled about 120 volunteers thus far.
“We’ve got a lot of infected people and a closing window of time,” said Merigan, professor of medicine at Stanford University and director of its AIDS research center. “We have to break through this denial. We have to get them to see how important the answers from this trial are in their future. Any time someone slides into disease without participating in the trial, everybody loses.”
One rare patient who agreed without hesitation to volunteer, a 34-year-old Pittsburgh man who is a father of three but asked not to be named, said he understands why others are reluctant but does not share their feelings.
“I know that as long as you don’t have to deal with it on a day-to-day basis, you can just put it out of your mind,” he said. “But my mother always said that if we could help in any way, it was our duty--because whatever we did to help would eventually help us.”
But physicians who treat hemophiliacs said that some have refused to join the study because they do not want to take the chance that they will receive a placebo, especially because many doctors will prescribe AZT on demand even though it has not been approved for individuals without symptoms.
Levine, for example, said that if his patients ask him, he will prescribe it for those infected individuals without symptoms whose count of T-4 “helper” cells is low--a clear sign that the virus has damaged the immune system.
He supports the study and has done his best to persuade his patients to participate, “but if someone says to me: ‘I want the drug, not the trial,’ I don’t think it’s ethical for me to deny him the drug,” he said.
Refuse to Be Tested
Compounding this is the refusal of many hemophiliacs to be tested for AIDS infection. About one-third of the hemophiliacs in the nation refuse to be tested, said Alan Brownstein, executive director of the National Hemophilia Foundation, another sponsor of the study.
“We have people who feel healthy and don’t want to face the potential of knowing they’ve been exposed to a deadly virus,” he added. “We also have other people--a large percentage--who are concerned about potential discrimination. People have told me they are more fearful of social isolation than they are of death from AIDS. It’s quite staggering when you hear that.”
Dr. Ed Gomperts, director of the hemophilia center at Children’s Hospital of Los Angeles, said that the majority of his adult patients “want to be tested and want to know” but that the “denial is still persisting” among parents of hemophiliac children.
“There are some families who say they just don’t want their kids to be tested and that’s it,” Gomperts said. “It’s purely because of the fear of ostracism, not fear of the disease.”
Gomperts, however, has some reservations about placing children in the study and does not push hard to enroll them, even though the trial will accept children older than 12. He has some concerns about the potential effects of the drug on growth and development and will not encourage any to join who have not yet entered puberty.
“But for those who have completed adolescence, I do try to get them onto the study,” he said. “I believe in the study. I believe the information is needed.”
Dr. Margaret Ragni, director of the hemophilia center of western Pennsylvania and an assistant professor of medicine at the University of Pittsburgh, said that an additional problem in attracting patients to the study may exist in yet another form of denial--that experienced by some physicians who treat hemophiliacs.
Close to Patients
“These are care providers who have been seeing these patients for years, since many of them were children,” she said. “They know the mother, the father, the brothers and sisters--it’s a relationship that grows up with the patient. So all of this is devastating, not only to the patient, but to the care provider--because now these patients may get sick and die.”
Physicians, she said, occasionally “have tremendous difficulty dealing with their own emotional stuff. And if you’re not quite through that, it will be difficult for you to sit down with a patient face to face and say: ‘Look, you and I both know you are infected. It may mean that somewhere down the line you might develop AIDS’--and then talk about the study. If a patient says no to the study, then you don’t have to talk about death and dying.”
She said that many may also be feeling guilty, even though “they weren’t responsible for letting AIDS get into the supply.” Nevertheless, she added: “It was their order that prescribed it. I’m not a psychiatrist, but it seems to me those are issues that you have to work through and get beyond.”
Ragni said that she has enrolled about 16 patients in the study, though she said “it was very difficult.”
She encouraged those patients who refused “to act as consultants to me” to help her understand their feelings about the research. “I’d say: ‘I really need your perspective.’ Sometimes it helps for them to be able to step outside themselves and look at their feelings. As a result, I’ve had a couple change their minds.”
Most of the researchers believe that others also will change their minds. But they are painfully aware that the clock is ticking while they wait.
“You can deny it for only so long,” Gomperts said. “Eventually, they will have to come to grips with it.”
The Pittsburgh man--one of Ragni’s patients--agreed.
“I’d like to see my kids graduate from high school,” he said. “I’d like to see them married. I’d like to hold my grandkids. This study gives me the one chance that I might have to do all those things.”
