Getting on the List
Persons with HIV Struggle for Transplant Access
Alan Hext, a person with HIV who broke new ground when he received a liver transplant in December 1998, is alive and well a full year later. Doctors say that his new liver is functioning perfectly. Hext now weighs a robust 180 pounds, and his CD4 cell count has gone up from around 300 at the time of the transplant to 435. His HIV viral load, meanwhile, remains undetectable. Hext is one of a very few persons with HIV to receive a liver transplant from Pittsburgh University. One other patient survives; two have died.
When one looks at Hext one sees a large, strong, healthy man -- not a dying liver or AIDS patient. His amazing survival story recently appeared on the front page of USA Today. Hext said that in the last year his health has been fine, with only a few complications from minor infections. He was hospitalized once following an infection arising in the aftermath of a dental abscess excision. Hext now lives in Palm Springs, California, with his family and a new baby boy.
Hext's two-year battle to get a liver transplant occurred just as the medical community was beginning to view asymptomatic HIV disease as a chronic manageable illness. Convincing surgeons and insurance companies that healthy people with HIV should be treated like any other chronic disease group was a long uphill struggle for Hext.
The Growing Demand For Organ TransplantsVarious surveys have found that deaths in the HIV community are down 60 to 75 percent since the 1996 introduction of highly active antiretroviral therapy. Yet certain intractable health problems remain. At the University Hospital of Cleveland HIV clinic, for example, liver and other organ failure accounted for half (sixteen) of the 32 deaths in 1999. (In 1995, 17 percent [or nineteen] of 115 deaths were from organ failure.) More and more, patients are facing emerging organ complications as they grow older. Lung infections, cancer, hepatitis B and C, HIV-associated metabolic derangements, and the long-term toxicities of antiviral drugs continue to take their toll. Organ transplants could save many of these people, but transplant doctors have considered patients with HIV too risky a group for their valuable time and precious free organs.
One study carried out in the 1980s under Dr. Thomas Starzl found that people with HIV and AIDS survived transplants but eventually went on to die from the standard AIDS-related conditions.
The progression to AIDS and death was only slightly more accelerated than the usual course of the disease at the time. Even though there were no effective treatments for AIDS or HIV, Starzl concluded that organ transplantation in persons with HIV needed to go forward. The transplant community in general did not accept his opinion, but United National Organ Sharing (UNOS) refused to exclude HIV-positive patients from its organ waiting list.
Dr. John Fung, a leading transplant surgeon at the University of Pittsburgh, was the only surgeon willing to try further liver transplants in HIV patients through the 1990s. Fung's group had always been seen as more radical than the rest of the organ transplant world. His colleagues like to refer to him as a "cowboy." Fung, who is Asian and grew up in Los Angeles, did not have the more traditional conservative views harbored by most organ transplant surgeons. "I think that anyone who needs a transplant and has a five-year life expectancy should get a chance," he said in a 1996 interview. Fung even advocated that patients on death row should be eligible for transplants if they needed a new liver.
Hext was introduced to Fung by advocates from ACT UP/Golden Gate (now Survive AIDS) in San Francisco. At the time, it was becoming painfully clear that he would not get a liver transplant in the state of California. Similar situations were occurring in other parts of the country. Another patient, Gary Bent, checked into a large New York City hospital with liver failure. Although there was a liver ready for him in the cooler, his surgeons essentially left him to die when they discovered his HIV status at the last minute. An HIV antibody test had been performed without his consent. Bent's family was outraged and filed a formal complaint with the hospital. The hospital was unapologetic, saying that it would have been a waste of a good organ. The family had heard about John Fung and transferred the then-comatose patient to Pittsburgh. By the time he arrived, no liver was available, and Bent died shortly thereafter.
Following Hext's denial in San Francisco, activists turned up the heat and staged a large, noisy demonstration on the front lawn of the University of California's Moffit Hospital. A symbolic coffin was placed on the ground and demonstrators formed a picket line. To the hospital's chagrin, public officials and city politicians joined the demonstrators. Shortly after that, the University agreed to move ahead quickly and create a liver and kidney transplant protocol. Anxious to make good, doctors performed a liver transplant on a person with HIV in May 1998. But it turned out that the patient had an unsuspected brain disease (PML), and died just two weeks later. By this time, it was clear to all parties that the only way to move ahead with organ transplantation in HIV would be to form a partnership between HIV researchers and organ transplant surgeons.
Under the leadership of Drs. Michelle Roland and Peter Stock, an HIV transplant protocol began to take shape at the University of California San Francisco. The Director of the University's AIDS Research Institute, Dr. Thomas Coates (who is himself HIV-positive), took a personal interest in moving the protocol forward. He persuaded the National Institutes of Health to convene a national working group, and several sites began collaborating. At the same time, Dr. Fung was refining his procedures and proceeding cautiously. He also joined the NIH team, and his unit became an NIH transplant site.
The University of California announced in February that a $1 million grant had been forwarded to its hospital to begin an HIV organ transplant pilot program. UC's press release stated that funds were available to study safety, efficacy, and long-term benefits of the organ transplant in seven HIV-infected patients. Coates has asked the State of California to fund another $1 million for next year. "Coming out of the recent Retrovirus Conference, rates of cirrhosis and end-stage liver disease double with HIV and hep C co-infection. Given that the medications are holding . . . it's essential that we prove as quickly as possible that it's safe for people with HIV to get organ transplants," Coates said. There have been no other large state or federal allocations. Fung and other members of the protocol team are seeking grants and third-party coverage.
Transplant Availability Still LimitedThe nearly complete NIH protocol may always be a work in progress. Unlike HIV drug trials, transplant protocols can be adjusted in midstream. The goal is to find a way for as many patients as possible to survive. "Proof of principle is what we're after," commented Fung. There are four sites so far: University of California San Francisco, Mt. Sinai Hospital in New York, University of Maryland, and Pittsburgh University. "This is really taking off," Coates remarked in a March interview. All four sites are either up and running or close to screening their first patients. Northwestern University is currently considering becoming a site as well.
Unfortunately, none of the sties will get NIH funding to pay for the actual transplants -- the NIH does not pay for "procedures." Instead, the sites will rely on private grants and third-party payers. Coates said that the NIH did agree to grant $150,000 to pay for data collection and some lab work, which will be done free in Chicago, it turns out. Coates also mentioned that he is asking Roche Pharmaceuticals for a grant for more scientific research. Insurance has paid for some HIV-positive organ transplants in the past, and the University of Pittsburgh has become very skilled at obtaining payment.
Coates said that UC will try to stretch its grant money by getting third-party reimbursement whenever possible. With a little luck, UC could complete as many as ten transplants in the next two years. It has asked for funding from the state for next year as well. Dr. Peter Stock, who is a transplant surgeon at UC, indicated that demonstrating the safety of these transplants will establish "proof of principle." Patients can then expect normal third-party payment.
UC's pilot study, which is nearly identical to the other three sites, will be restricted to those patients who have had no major opportunistic infections and whose CD4 cell counts are stable and above 200 for kidney candidates, and over 100 for liver candidates. In both organ groups, patients must have very low or undetectable plasma viral loads (less than fifty copies of HIV RNA/mL) through a strictly followed antiviral treatment regimen. Criteria for other sites may vary in that they will allow lower CD4 cell counts and some history of opportunistic infection. Once a patient has been selected, he or she must go on a waiting list until an organ becomes available. Alternatively, patients can use relatives as donors. Waiting times vary from site to site. Hext's wait was under one year. Depending on a patient's blood type, the wait in San Francisco could last up to three years.
UC already has received many inquiries from potential organ recipients. "We are getting overwhelmed," said Stock. Stock is concerned that the liver patients will not remain in good health for three years. Stock and Fung are looking into procuring unwanted high-risk organs. Although national waiting list rules are changing so that the sickest patients will always be at the top of the list, some sites may remain reluctant to prioritize HIV and hepatitis C patients ahead of healthier candidates with a better life expectancy.
Dr. Stock says that his site will try to emphasize high-risk organs and living-donor-related livers. In a living-donor transplant, a lobe of a living person's liver is removed and placed in the patient. If all goes well, both donor's and patient's liver portions will regenerate to nearly normal size in about two months. Such transplants can take place without placing the patient on any waiting list.
Initial Experiences Under the New ProtocolStock's site in March performed a living-donor liver transplant on a 15-year-old southern California boy. Stock noted that this transplant went quite well, but he warned that these procedures are risky. "We have had two donor deaths nationally so far," he said. Some surgeons will be reluctant to pursue living donors when the patient has both HIV and hepatitis C or B.
The first kidney transplant candidate for the UC study died unexpectedly last fall while still on the waiting list. On April 7, a kidney was transferred from a living donor into a middle-aged HIV-positive man. This operation was a success, and Stock was planning to send the patient home from the hospital soon thereafter.
Several more candidates have been screened and will be placed on kidney waiting lists. At least one HIV patient is now at the top of the waiting list and will most likely receive a new kidney within a month or two. Dr. Robert Scott, an Oakland, California, practitioner and this patient's HIV doctor, helped get him through the screening process some time ago. "I'm excited. This is a patient who is in good health with 500 CD4. He has HIV-related kidney necrosis," said Scott. "This patient hated dialysis. He was so depressed that he wanted to go off [dialysis] and die." Scott sees this kidney transplant as a life-saving issue -- even though there is substantial risk to the first patients. "You deal with risk versus benefit. I think in this case, the benefit outweighs the risk," he remarked.
Pittsburgh has performed four liver and two kidney transplants on HIV patients since 1995. One liver patient died of a postoperative bacterial infection. All the other patients are doing well, according to Fung. Fung's biggest problem has been recurring hepatitis C and B after transplant. He treats the hepatitis C with interferon and ribavirin. Pittsburgh will continue to transplant healthier asymptomatic patients, though probably some of the patients will be a little sicker than the ones UC will accept. "None of our liver patients had T-cells over 200. Now they have all gone up into the 400s," he mentioned.
Fung has had one patient whose HIV doctor mistakenly took him off a protease inhibitor without checking with the transplant center. Protease inhibitors decrease the body's clearance of antirejection drugs. "The PK [drug level] work here is so critical," Fung remarked. Because antirejection drug levels fell in the patient off the protease inhibitor, his body began rejecting the liver. "That kind of stupid mistake should be avoided," he said.
It is still touch and go for this person. Fung believes that they caught the rejection early enough to save the liver, and the patient is improving. Fung and Stock agree that once a patient is transplanted, all medication adjustments must be made through the transplant centers. "Otherwise there may be irreversible damage," said Fung.
Obtaining TransplantsAt least one liver transplant death could have been averted had the patient not pushed so aggressively for the transplant. Once antirejection medication is taken, there is a very good chance that any smoldering unknown infection could break through and cause problems. Liver disease patients need to understand that anyone in a weakened state due to advanced immune dysfunction and opportunistic infections is not likely to survive the transplant procedure. Anyone with HIV considering a kidney transplant might want to wait a year or two if their condition is not life-threatening. Falsifying past medical history and trying to "fudge" into this study could be a deadly mistake.
It is likely that the University of California San Francisco pilot program will have more patients than available slots. Dr. Peter Stock can be reached at UCSF by calling (415) 353-1117. Patients who urgently need transplants may also contact Dr. John Fung at the University of Pittsburgh, (412) 648-3200, and Dr. Barbara Murphy at Mt. Sinai, New York, (212) 241-5850. Information about the NIH multisite protocol is available through Dr. Thomas Coates's office, (415) 597-9175. Patients who have difficulty obtaining help may also contact Survive AIDS at (415) 252-9200 to ask for advocacy.
This article originally appeared in April 2000 in the amfAR treatment website, www.amfar.org/treatment. It is reproduced here with permission of amfAR and the author.
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