Drug Experiment : With AIDS, Even Hope Can Be Cruel

It had been eight months since the last episode, but the symptoms were frighteningly familiar. AIDS patient Jeffrey Mullican knew, with a permeating dread and foreboding, what was happening.

First came the persistent fever and sore throat, too painful for him to talk or swallow. Then the shortness of breath, accompanied by fatigue so overpowering that he had to hold onto the walls while taking a shower. At night he would put on a heavy sweat shirt, wrap himself in an electric blanket and curl into a ball on his bed in a futile attempt to ward off the bone-penetrating chills, only to awaken an hour later so drenched in sweat that he could wring out his shirt in the sink.

“The party’s over,” he said recently as he sat shivering in his warm apartment, bundled in a down jacket. “Reality sets in.”

He knew it was pneumocystis carinii pneumonia again--one of the rare and insidious infections that characterizes AIDS--even before his physician, Dr. Robert T. (Chip) Schooley, could confirm it. And he knew it meant his struggle with the usually fatal disease was far from over.

Mullican is gambling on the beneficial but experimental AIDS drug azidothymidine, or AZT, to keep him alive. The recent episode was for him another terrifying plunge into despair, a drop on the roller coaster ride of emotions that began last April with his first bout of pneumocystis and the numbing realization of what it meant: that he had AIDS.

Hope and Melancholy

Mullican had begun to feel some hope in May, as he began to participate in a nationwide clinical trial of the drug. In the double-blind, placebo-controlled study, neither the doctors nor the patients knew who was receiving the AZT and who was getting a medically worthless sugar pill. In September, that hope soared into euphoria when he learned that the drug was making dramatic impact in prolonging life--and that he had been taking the AZT all along.

But later, instead of embracing the unexpected gift of time, Mullican, a 32-year-old trade association executive who is gay, became engulfed in melancholia over his uncertain future. He was afraid to begin relationships or make major changes in his life. He found the ambiguities of his situation to be torture--like trying to adjust to a constantly moving target.

These feelings have been intensified by his latest setback.

“The potential of this happening was just too great,” Mullican said. “AZT is a promising drug, but there are too many unknowns. If it had a 10-year track record, then I could afford to give myself hope. If they could say: ‘Take this for the rest of your life and you’ll be fine.’ But they can’t. All they could say was: ‘The most positive thing is that you’re not getting sick.’ Well, now I’m sick.”

Schooley says that Mullican will recover from this latest infection, which was far less debilitating than his first episode, when he was hospitalized twice. This time he has been treated as an outpatient.

His psychological condition, however, is extremely fragile, weakened by the never-ending tug-of-war between hope and desperation.

“Some days I feel I would just rather die and get it over with,” Mullican said. “I don’t feel like I have any options, like the odds are so much against me--is it really worth fighting anymore? I just feel resigned to my fate. I just wish it would hurry up and take place.”

Then, yielding to the vulnerability he no longer tries to suppress: “This makes the uncertainty more certain. It reconfirms my thinking that I’m going to die sooner, rather than later. It’s not a relief. I don’t want to die.”

Doctor Not Surprised

Schooley, the 37-year-old infectious-diseases specialist at Massachusetts General Hospital with whom Mullican has established a special rapport, was discouraged over Mullican’s relapse, but not surprised. Other participants taking AZT in the national study have suffered recurrences of pneumocystis, a parasite-induced respiratory infection associated with damaged immune systems. Taking AZT seems to extend the period of time between bouts, slow the onset and make the episodes milder.

Indeed, before his latest illness, Mullican had enjoyed eight months free of any infection, which is unusual--although not unheard of--among AIDS patients.

“None of us expected AZT to have shown what it has shown. It changes the concept of AIDS as a death sentence,” Schooley said. “We’re keeping him alive, with fewer bouts of pneumocystis and less likelihood of other infections. If we can slow down the progression of things while we work on other options, I hope we can have a big impact.”

“But we still don’t know what the long-term trend is going to be,” Schooley said. “We’d be questioning our sanity if we saw no one on this drug have another infection.”

Virus Destroys Immunities

Acquired immune deficiency syndrome is caused by a virus that destroys the immune system and leaves the body vulnerable to ravaging infections, such as pneumocystis, and rare cancers. The virus can also invade the central nervous system and cause severe neurological disorders, such as dementia. It is a sexually transmitted disease spread by anal and vaginal intercourse and through the sharing of contaminated hypodermic needles.

It also has been spread via transfusions of blood and blood products--although the risk of the latter has been made slight by the use of a blood-screening procedure. In the United States, it has primarily afflicted homosexual and bisexual men, intravenous drug users and their sexual partners.

Since 1981, AIDS has stricken more than 29,000 Americans, of whom more than 16,000 have died. The number of cases is expected to reach at least 270,000 within the next five years. Until AZT, there was no treatment for AIDS.

“I’m still concerned that the (AZT) results are short term, and on a small number of people,” Schooley said. “We can’t let the short-term results go to our heads and say, ‘We have an answer--no one’s going to die.’ I’m certainly convinced of the short-term results. As a human being who cares about other people, I’m ecstatic about them. I hope I can be as happy six months from now.”

‘A First Step’

He added: “We have a crafty opponent in this virus. It’s most important to point out that nobody claimed this was a cure. We see this as a first step.”

In the meantime, Schooley remains worried about the impact of his latest infection on Mullican’s emotional state.

“This is going to shorten his psychological leash,” he said. “I’m very concerned he will see this as all of a sudden having his lifeline yanked and being left in the middle of the ocean. He’s scared all over again. That’s one emotion I’m not surprised to see, but I hope, as this episode gets further behind him, we can learn to deal with it.”

Dr. Alexandra Beckett, a staff psychiatrist at Massachusetts General Hospital who runs an AIDS support group that Mullican recently joined, believes Mullican is going through a kind of turmoil that is common among people faced with life-threatening disease.

One of her colleagues, she said, treated a patient who had melanoma, a frequently fatal form of skin cancer. “He was told if he survived five years, he would be cured,” she said.

Recurrence as Relief

“Four years and 11 months out, he had a recurrence--and he told her he was relieved. He had been living with the dread of a recurrence, and now he could finish things up--this invisible, intangible possibility was keeping him from functioning.”

Mullican, she said, “knows he’s going to get through this bout. He caught it very early--he identified it before it could be identified clinically. AIDS patients have a sense about when death is actually coming, and I don’t think he feels that time has come.

“He’s depressed about this because it’s an indication that AZT is not a panacea, and that he is vulnerable,” she added. “He’s been slapped in the face with the fact that he really has a fatal illness.”

Mullican is sitting on a gurney in one of the tiny rooms that make up the emergency area on the first floor of Massachusetts General Hospital. On this Saturday morning, two days after the recurrence of pneumocystis was confirmed, it is quiet and the emergency room personnel have time to stop and talk. Since the AIDS epidemic began nearly six years ago, there have been numerous horror stories of medical professionals shunning AIDS patients, refusing to touch them--but there is none of that here.

Mullican turns to a friend who has come with him: “Go outside and look above the doorway--see if there’s a ‘6’ over the door.”

The friend comes back and says that there is.

“I thought this room was familiar,” he says. “This is the same room I was in during my first bout. This is where Chip told me I had AIDS. This is where it all started.”

The physician on duty comes in, dons gloves and prepares to insert a small needle into Mullican’s arm. He begins a slow-drip intravenous of a clear solution of Pentamidine, the drug that will battle the pneumocystis while the AZT fights the underlying AIDS infection.

Intravenous Treatment Begins

The Pentamidine will take more than 45 minutes to enter his system. It will eventually wipe out Mullican’s current pneumocystis infection, and, in the meantime, it will wipe out Mullican as well. His breathing becomes labored during the treatment and he requires oxygen, which is filtered through water to humidify it and delivered through a plastic tube to nasal prongs. As the Pentamidine enters his vein, that arm becomes numb and cold.

About two hours after the therapy, Mullican suffers chills, nausea and extreme fatigue. Upon returning home, he vomits. He also suffers a local skin reaction near the needle puncture. Pentamidine causes side effects such as low blood pressure, low blood sugar and a reduction in white blood cells. Most physicians prefer not to use it, but Mullican is allergic to Bactrim, the preferred drug.

He will need at least 14 days of infusions. Midway through the course of treatment, Mullican’s white cell count will drop and Schooley will take him off Pentamidine for a day or two, to give his system a rest. By the end of the siege, Mullican--unable to eat because of his extremely sore throat--will have lost about 12 pounds and require occasional intravenous feedings. Although he will not be hospitalized, he will miss a month of work.

AZT Is Suspended

Last Wednesday, with his white cell count still low, he was told to stop taking AZT. A reduction in white blood cells is also one of that drug’s side effects. He was to find out this morning when he can resume taking AZT.

Mullican’s second round of pneumocystis symptoms appeared very slowly, beginning about two weeks before Thanksgiving. He suffered from fever, a sore throat and congestion, as well as fuzzy vision. He was examined by an ophthalmologist, who found nothing. Two chest X-rays were clear. Schooley considered ordering a CAT scan--a cross-sectional picture of the brain--to see if the vision problems could be attributed to an AIDS-related brain lesion, or lymphoma. Meanwhile, Mullican felt well enough to fly to Washington and spend Thanksgiving with his parents.

When he returned to Boston, he began feeling worse. A chronic skin condition on his face began to flare up, something that happens only when he is truly ill. He was convinced the pneumocystis was back.

“It’s striking how patients, after their first bout, know what the symptoms are for them,” Schooley said. “It’s a very good example of how doctors need to listen to what patients say.

“I had one patient who would get a stiff neck before she would get pneumocystis,” he continued. “She’d come into the emergency room, and they would want to do a lumbar puncture (to look for meningitis) and she would say: ‘No--I have pneumocystis,’ and the next week, she would have pneumocystis.”

Schooley ordered a third chest X-ray and it showed a distinct cloud beginning to form over the dark outline of Mullican’s lungs: a combination of white cells, fluid leaking from the inflammation and the microscopic parasites. Mullican’s infection could also have been influenza, or cytomegalovirus, another serious, AIDS-related viral infection. But the likelihood was greater than 90% that it was pneumocystis, since AIDS had first taken that form with him.

The difficulty with patients on AZT, he said, is that “we have no precedent for knowing how some of these AIDS-related infections develop. It may be that pneumocystis may take a longer time to develop to the point where it can be diagnosed.”

Although some AIDS patients experience long “honeymoon” periods of relief from pneumocystis, those who come down with it repeatedly typically survive no longer than 35 or 40 weeks.

Parasite Damages Lungs

Left untreated, pneumocystis is fatal. Pentamidine does not kill the parasite’s egg-like cysts, which remain in the lungs and can cause trouble again later. With each episode there is some irreversible lung damage.

“It may be that they don’t do well after the second or third bouts because of damage to the lungs the first time, or because of their worsening immune system--and it’s also possible that the organisms develop a resistance to the drugs,” Schooley said.

With AZT, this process of deterioration seems to have been significantly slowed. Of the approximately 140 patients in the original nationwide study, 16 patients on the placebo and one who was taking AZT had died by the time the study was stopped in September. At that time, those on the placebo also were given the drug.

According to Dr. Samuel Broder, chief of the clinical oncology program at the National Cancer Institute, who did the early work on AZT in the laboratory and on patients, 17 months is the longest that patients on AZT have survived. People on AZT, Broder said, “still are at risk of acquiring infections.” Further, Broder said, with patients who have fully developed AIDS, “it is not unexpected that the drug can only do so much.”

Comparison to Leukemia

Schooley likened the current stage of the battle against AIDS to the early days of research on children’s acute lymphatic leukemia in the 1950s, when a single drug was used. It induced remissions in many patients, but many relapsed later.

“Over the course of the years, the oncologists learned to combine various agents that increased the likelihood of getting a full-blown cure,” he said. “Now, it’s a disease we do pretty well with.

“We’re at the same point with AIDS as we were with the single-agent (leukemia) therapy then,” he said. “If we learn how to add additional drugs, or use AZT in a more insightful way--or both--we might begin to have a more lasting effect on this disease. My hope is that this is what will happen with patients like Jeff.”

Mullican’s attitude now seems a far cry from the combative yet realistic attitude he adopted after he joined the study last May. He vowed then to “beat this disease,” but nevertheless tempered his denial with the harsh truths reflected in the burgeoning AIDS death statistics. Hoping for the best and assuming the worst, he took his capsules--contents unknown--every four hours. And he tentatively began the process of putting his affairs in order, saying goodby to family and friends and places in his past.

Then the roller coaster surged upward again, with the news that AZT was proving helpful and that he was one of those taking the drug. Schooley also told Mullican that his treatment would become more flexible--that Mullican need not remain in Boston, as the original rules of the AZT study had required.

He could begin to live again. Or could he?

For more than four months, Mullican’s existence had revolved around the clinical trial. He had been restless in his work and unhappy in Boston, but his battle with AIDS and his participation in the study had relieved him of having to deal with those frustrations.

Freedom Posed Problems

Suddenly, everything had changed: He was free to leave, to look for another job and move to a different city. And he began to make gestures in that direction.

“Before, my attitude was: ‘Let’s live one day at a time and see what happens in six months,’ ” he said some weeks ago. “There was a certain degree of security in the study. The problems that existed in my life before I had AIDS were put aside as not important, as I prepared myself to die. Now I have to prepare myself to live.”

He found that an equally terrifying process.

“Am I physically able to do it?” he asked, as he began sending out his resume in October. “I can’t start a new job with major responsibilities--then call in sick the following week.” One potential employer, unaware that he has AIDS, asked him during an interview if he had a five-year plan for himself.

“I laughed in my head,” Mullican said. “If she only knew what has happened in my life in last eight months, she would realize how ludicrous her question was. I don’t have the luxury of having a five-year plan. My luxury is having a five-day plan.”

He also began to avoid relationships, old ones as well as new. Some of his Boston friends, he said, have described him as “too negative--they say I bring them down.” So he began seeing them less and less, preferring to be alone.

AIDS ‘Buddy’ a Friend

His only regular companion has been Henry Weinberger, 33, a Boston musician who is the “buddy,” assigned to him several months ago by the local AIDS Action Committee, a Boston-area service organization.

“I’m somebody to talk to, especially if it’s an AIDS-related sort of thing,” Weinberger said. “He might be less apt to talk to someone else about it, but part of the given is for a ‘buddy’ to be receptive to talking about AIDS or anything.

“It’s a friendship that comes out of his being sick, and that puts a different cast on it,” Weinberger continued. “The beginning had an artificial start, but it’s natural for it to become a friendship.”

Mullican dropped out of his first AIDS support group several months ago because he felt that he no longer belonged. It had become too painful, watching the others die one by one, wondering if he was staring at his own fate. At the same time, he said, some members resented him because he was getting AZT and doing well--and they were not.

“One of the guys said, ‘You don’t hurt--you’re not in pain’ ” Mullican said some weeks ago. “I would leave the group feeling worse than when I came. His name was Vic, and he was in his 20s. He had pneumocystis. He’d tried to get into the AZT program--before they opened it up--but couldn’t. He died in September.”

Self-Imposed Loneliness

Mullican feels lonely, but recognizes it as a self-imposed isolation.

“All I ever really wanted was a close relationship--more the psychological and emotional than physical,” he said. “And now I can’t do it on either level, because I’m afraid I’m going to lose it. Who in his right mind would want to get involved with someone who has AIDS?”

Psychiatrist Beckett, who leads the group Mullican joined shortly before he developed pneumocystis, said his reaction was typical. “These people feel contaminated and undesirable,” she said.

Not surprisingly, Mullican’s second bout with pneumocystis has caused him to abandon his job search, at least for now. Just before Christmas, as his Pentamidine therapy ended, he agreed to an out-of-town interview with a prospective employer--but canceled the appointment at the last minute because he still felt weak.

“How can I change jobs?” he said. “I demand 200% of myself--and I can’t give 200% when I feel this way. And I hate where I am now. I feel like I have no options.”

Earlier, before Mullican bowed out of the interview, he had said: “If I’m offered the job, I’m going to level with them. I have to tell them I have AIDS. I’m not quite sure how I’m going to phrase it. Maybe I’ll just come out and say it. I wonder if there’s a less devastating way to say it. I can’t see why an employer would want to hire someone he thought might only be around a year or two.”

Doctor Backs Planning

Schooley understands Mullican’s frustration and his sense of desperation. Yet, he continues to urge him to look beyond the present.

“I still think Jeff needs to think about his long-term desires and goals in life and act on them,” he said. “We don’t know if he’ll get another bout of pneumocystis. We don’t know if we’ll have other drugs which may be even better than AZT. Even if he stays on AZT, we don’t know whether, with prolonged treatment, his immune system might gradually improve. We don’t know if things will break in his favor--but it will be a tragedy if he spends the next 10 years of his life afraid to act on anything.”

Schooley paused. “He’s living with a lot of uncertainty, more than he was living with eight months ago, when he was diagnosed. But the uncertainty he is living with now is because of a good result, not a bad one. The uncertainty makes it hard for him to approach a lot of things that come up every day, but we all face uncertainties in our lives.

“Still, for Jeff, the uncertainty of now is better than the certainty of then.”