Transplantation in HIV-positive Patients?
Latest update from University of Pittsburgh
from John Fung, MD, PhD, 06/28/01
We have done a total of 7 liver transplants and 4 kidney transplants in the HAART era. At the time of the writing of the original response (February 2000), 1 patient had died relatively early (2 weeks after liver transplantation) due to poor graft function and requirement of life support prior to surgery. Since then, we have had 1 additional death at 20 months due to chronic rejection in a patient who became "noncompliant" when the protease inhibitor was discontinued without appropriate adjustment of tacrolimus levels (unbeknownst to the transplant team), with resultant rejection. The remaining 9 patients are all alive with stable HIV disease. We are publishing the results of our 7 liver patients with the 5 from Miami, Florida. None of their patients has died. We have submitted this to The New England Journal of Medicine.
I received a verbal report recently from French researchers that they have performed 3 liver transplants which appear to be successful so far with limited followup. At the 2001 Restrovirus Conference negative results were reported from transplants in the UK. so, results appear to be mixed but I think promising. It does appear that Pittsburgh has a better record of success.
from John J. Fung, MD, PhD, 02/29/00,
Transplantation Section at the University of Pittsburgh
In spite of the many advances in organ transplantation, the presence of HIV in a patient has been considered a contraindication for transplantation. The following summarizes the current concerns: (1) a stable HIV-positive candidate will immunologically decompensate with immunosuppression; (2) the viral load will increase and/or immunosuppression may enhance HIV mutations; (3) the pharmacokinetics and pharmacointeractions of current antiretroviral agents and immunosuppression may lead to subtherapeutic effects or toxicity; and (4) the public perception of offering transplantation to HIV-positive patients will lead to diminished support for donation.
Since 1997, the vast majority of antiretroviral therapies for treatment of human immunodeficiency virus type 1 (HIV) infection have included multiple drug therapy. Highly active antiretroviral therapy (HAART), consisting of 2 or more nucleoside analogues (NRTI) plus 1 protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI), has been shown to be associated with significant stabilization of CD4 counts and lower mortality. Because of these advances, the University of Pittsburgh transplantation program has been a leading advocate for patients with HIV to be considered for organ transplantation. The world's largest experience with transplanting HIV-positive patients is at the University of Pittsburgh.
Since the advent of HAART therapy, 4 patients have received liver transplantation (OLTX) at the University of Pittsburgh between September 1997 and March 1999. All patients had liver disease secondary to HCV infection. One patient with advanced liver failure, manifest by ventilator dependency and renal failure, died 12 days following OLTX from bacterial infection (not related to HIV). Three other patients have survived between 9 and 27 months. While HCV recurrence requiring ribavirin and interferon therapy was required in all surviving patients, all have excellent liver function. All patients remain on HAART with PI and HIV loads have remained undetectable in all patients during the entire follow-up period. No patient has developed an opportunistic infection. Total CD4 counts, which were all < 200 cells/mm3 prior to OLTX, improved to > 200 cells/mm3 following OLTX. PI use was associated with significant cytochrome P450 3A interference. Tacrolimus dosing was markedly reduced to minimize levels of tacrolimus and resultant toxicity.
Two patients with renal failure received kidney transplantation during the same period of time. Both had cadaveric kidney transplantation with good function and both have received a variation of HAART therapy, based on NNRTI. HIV loads have remained undetectable in both patients during the follow-up. Neither patient has developed an opportunistic infection, and all CD4 counts have remained > 200 cells/mm3 during the posttransplantation period.
This limited experience suggests that organ transplantation is effective in selected HIV-positive patients. There should be further accrual and follow-up of these patients to assess long-term benefits and risks. We, therefore; propose that a national registry be created to accrue sufficient data for such analysis.
Thanks to Medscape.