Key Clinical, Ethical, and Policy Issues in the Evaluation of the Safety and Effectiveness of Solid Organ Transplantation in HIV-Infected Patients

HIV patients are at significant risk for end-stage kidney and liver disease, and therefore potential candidates for organ transplantation. Pre-HAART, they were considered poor transplant candidates due to HIV-associated mortality and the possibility that post-transplant immunosuppression might accelerate HIV progression. Now that HAART has dramatically decreased HIV/AIDS mortality rates, issues surrounding transplantation in HIV patients must be addressed.

The current study describes the key clinical, ethical and policy issues related to the study of transplantation in HIV patients. Since organs are in high demand and availability is scarce, expanding the population eligible for transplantation raises ethical concerns. Some argue that diverting organs from a group likely to benefit from transplants to a group for whom the benefits are unknown could result in deaths among patients on waiting lists without benefiting the organ recipients. The authors support outcomes data to determine whether HIV patients should be given similar priority to other patients eligible for transplantation. "We believe that the question of transplantation in HIV-infected patients should be decided according to rigorous clinical data," they stated. "Therefore, we have initiated a 'proof of concept' clinical trial of liver and kidney transplantation in selected HIV-infected patients."

To be fair to potential subjects, the scientists adopted a "proof of principle" approach to participant selection. The study is evaluating the hypothesis that immunosuppression neither accelerates the progress of HIV disease nor reduces survival in subjects with a relatively intact immune system and good HIV suppression. "If such a population has a good outcome," the authors noted, "selection criteria will be modified as the study progresses to test the same hypothesis in patients with more advanced immune dysfunction (e.g., a history of opportunistic disease or a lower CD4 T-cell count) and/or less well-controlled HIV replication."

During the first phase of the study, the researchers excluded patients with a history of neoplastic complications or infectious opportunistic infections. However, the protective immune reconstitution conferred by HAART, and the fact that many potential transplant recipients have a remote OI history, led the authors to change their criteria after the first 20 patients had been followed up for six months. Currently, subjects with specific OI histories are included.

Transplant candidates with drug-resistant HIV who are not predicted to fully suppress viral replication after transplant are excluded at present. HCV-infected patients are included in the trial, because the high prevalence of HIV/HCV coinfection makes determining the safety and efficacy of kidney and liver transplants among this population a pressing issue.

The authors noted that although preliminary experience with transplantation in the HAART era appears promising, ethical and clinical questions remain. "To address the concerns of utility and survival rates deemed acceptable, the minimum patients and graft survival rates deemed acceptable, based on current transplantation practices, must be defined," they asserted. "Clinical outcomes data from well-designed trials are critical to promote adhesion to the principle of justice in the organ allocation process. The process of including HIV-infected patients in a clinical trial should occur as publicly as possible. In this way, all stakeholders will be able to participate in discussions focused on excellence in patient care and driven by well-designed and ethical clinical and basic research," they concluded.

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