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Organ Transplantation

August 2001

As people live longer due to using potent anti-HIV therapy, there appears to be an increase in the percentage dying from non-AIDS defining conditions, including organ failure. Long-term infection with hepatitis B or C can lead to liver failure. Some research suggests that liver disease is accelerated when a person is also fighting HIV. Transplantation is virtually the only option for people with severe liver disease. HIV-related kidney diseases, specifically HIV-associated nephropathy, is of major concern to African Americans and represents the third leading cause of end-stage kidney failure in African American adults. Other causes of organ failure may include side effects of therapies to treat HIV and associated conditions. In cases of organ failure, transplantation is the only viable option. For people with kidney dysfunction, dialysis may provide a short- or even long-term solution. For people with HIV experiencing organ failure, transplantation needs to be an option.

Current guidelines make it difficult for people with HIV to get organ transplants. While groups that distribute organs will include people with HIV on waiting lists, most surgeons will not transplant an organ into a positive person and third-party payors will often not pay for them. These policies, which assume that positive people will all die in a relatively short time, were put in place during an era when little was known about HIV disease and today's potent therapies were not available.

In recent years community activists and researchers have been working together to move the organ transplant field to reassess this issue and reconsider organ transplantation for people with HIV. Previous information suggests that people with HIV undergoing organ transplants may have a poorer outcome (11% lower survival rates) than people who are not infected with HIV. Whether this holds true today, when people with HIV are living longer and experiencing fewer opportunistic infections, needs to be examined. As a result a group in Pittsburgh has agreed to perform a number of these transplants and a group at the University of California, San Francisco (UCSF), in strong collaboration with the Pittsburgh group, is spearheading efforts to develop a nationwide study to make available and evaluate organ transplantation in people with HIV. Some individuals, on a case-by-case basis, have had success in convincing institutions to perform organ transplants for them, despite their HIV status.

A group in the United Kingdom (UK) examined eight people with HIV who underwent liver transplantation at King's College Hospital in London. Five of the transplant recipients were experiencing end-stage liver disease (ESLD), four associated with hepatitis C and one with hepatitis B. Three were experiencing liver failure, two associated with hepatitis B, one associated with hepatitis non-A or non-B.

Of the four transplant recipients who had ESLD associated with hepatitis C, all died following transplantation (at 3, 6, 15 and 25 months). CD4+ cell counts in this group ranged from 160 to greater than 500. Of the two individuals with viral load measures available, both had well suppressed HIV levels, one below 400 copies/ml and the other at 965.

Of the four transplant recipients who are alive, CD4+ cell counts at time of transplantation ranged from 124 to 293; none had well-controlled HIV levels at time of transplantation with measures ranging from 25,000 to 197,000 copies/ml. Currently these individuals have been alive 1, 5, 15 and 35 months following transplantation. Of the four people alive today, three have reported CD4+ and viral load measurements (the fourth, alive one month post transplant, did not have measures available at time of data presentation). In all cases, CD4+ cell counts rose and in all cases HIV levels are well controlled, two to below 50 copies/ml and one to 64 copies/ml.

The observations from the UK group suggest that the cause of liver disease, and the subsequent ability to control that disease with medications following transplantation, may be more important than HIV-related immune and virologic characteristics in predicting who might best respond to liver transplantation. These findings support re-evaluating inclusion criteria for the proposed US study, allowing people with measurable viral load in the study. More work is needed to determine who with hepatitis C might best thrive following liver transplantation.

The team at the University of California has preliminary data from their pilot study for liver and kidney transplants. This study is the basis for a larger, multicenter project that is being developed. Inclusion criteria for people in need of liver and kidney transplants are slightly different. For kidney transplants, people must have a CD4+ cell count greater than 200, whereas for liver transplants CD4+ cell counts must be above 100. In both groups, volunteers must have undetectable viral load for three months prior to transplantation. Kidney transplant recipients must show no signs of serious liver damage (cirrhosis) associated with hepatitis C infection. Volunteers may not have had previous opportunistic infections (with the exception of treatment-sensitive candidiaisis) or cancers.

To date six individuals, one Latino, three African Americans and two Caucasians, have received transplants under this study, one liver and five kidneys. At the time of data presentation all six volunteers were alive, 40 to 315 days after their transplantations. The Latino man who received the liver transplant did have hepatitis C associated liver disease leading to the need for transplantation. Following transplantation his hepatitis C virus levels have been controlled with ribavirin and interferon-alpha therapy. Not long after data presentation, however, this man died due to transplant complications not associated with HIV. Of note, two volunteers discontinued anti-HIV therapy for short periods of time following transplantation. This resulted in minimal and delayed return of measurable HIV levels. It is theorized that the immune suppressive therapies used to prevent rejection of the organs (mycophenolate and cyclosporine) may have some direct or indirect anti-HIV activity.

It is expected that the multicenter organ transplant project will receive funding early next year and will be available to more people with HIV across the country. Efforts are being made to include heart transplantation in this project as well. As the epidemic changes, new areas of activism and research are emerging as high priorities. Organ transplantation is one such area.


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