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Transplantation in HIV+ Recipients

Transplantation in HIV+ Recipients

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Transplantation in HIV+ Recipients

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  1. Transplantation in HIV+ Recipients Ron Shapiro, M.D. THOMAS E. STARZL TRANSPLANTATION INSTITUTE UNIVERSITY OF PITTSBURGH

  2. Transplantation in HIV+ Recipients Prior to 1996 - • HIV+ = AIDS • Transplantation formally contraindicated • Median survival for HIV+ patients on dialysis – 10 months. Thomas E. Starzl Transplantation Institute

  3. Transplantation in HIV+ Recipients Tzakis – Pittsburgh Experience 1981-1988 N – 25 Pediatric – 10 11 - Infected Pretransplantation 14 - Infected Peritransplantation PatientsSurvivors Liver 15 7(43%) Kidney 5 4(80%) Heart 5 2(40%) Thomas E. Starzl Transplantation Institute

  4. Transplantation in HIV+ Recipients Pediatric – 70% Survival One Death from AIDS Adult – 40% Survival 5 Deaths from AIDS However, survival not statistically worse than in HIV- recipients. Thomas E. Starzl Transplantation Institute

  5. Transplantation in HIV+ Recipients Minnesota – 1990 N – 21, 5 local and 16 from literature Kidney – 11 Liver – 10 Thomas E. Starzl Transplantation Institute

  6. Transplantation in HIV+ Recipients Kidney 3 – Died of AIDS 6/8 (75%) – Normal graft function at 2-1/2 years and no HIV-related complications. Thomas E. Starzl Transplantation Institute

  7. Transplantation in HIV+ Recipients Liver 90% mortality, 40% death from AIDS Thomas E. Starzl Transplantation Institute

  8. Transplantation in HIV+ Recipients USRDS – 1987-1997 • 32 HIV+ patients underwent renal transplantation • 0.05% of transplants Thomas E. Starzl Transplantation Institute

  9. Transplantation in HIV+ Recipients 1/3/5 Year Survival PatientGraft • HIV+ 97%/83%/71% 81%/53%/44% • HIV- 95%/88%/78% 85%/73%/61% p<.05 at 3 years for GS, 5 years for PS/GS Main causes of death in HIV+ patients – infection, cardiovascular disease Thomas E. Starzl Transplantation Institute

  10. Transplantation in HIV+ Recipients Acute Rejection • HIV+ 50% • HIV- 48.4% Thomas E. Starzl Transplantation Institute

  11. Transplantation in HIV+ Recipients Cyclosporine → Lower Incidence of AIDS 31% versus 90% at 5 years Inhibition of HIV Replication Binding to HIV -1 Gag protein Thomas E. Starzl Transplantation Institute

  12. Transplantation in HIV+ Recipients HAART – 1996 Highly active antiretroviral therapy HIV+ ≠ AIDS Thomas E. Starzl Transplantation Institute

  13. Transplantation in HIV+ Recipients If HIV+ ≠ AIDS Why deny transplantation to HIV+ patients? Thomas E. Starzl Transplantation Institute

  14. Transplantation in HIV+ Recipients HIV-Associated Nephropathy (HIVAN) – Third leading cause of ESRD in African-Americans 20-64 years of age HIV+/HCV+ → accelerated progression to ESLD Thomas E. Starzl Transplantation Institute

  15. Transplantation in HIV+ Recipients HIV+ Patients on Dialysis Survival – USRDS 1 Year2 Years 58% 41% 32.7% One Year Mortality Thomas E. Starzl Transplantation Institute

  16. Transplantation in HIV+ Recipients Inclusion Criteria Undetectable viral load (< 400 or <50 copies/ml) CD4 count >200 cells/mm3 Thomas E. Starzl Transplantation Institute

  17. Transplantation in HIV+ Recipients Kumar – Hahnemann N- 40 2/01-1/04 (97% African-American) Survival 1 Year2 Years Patient 85% 82% Graft 75% 71% Viral load undetectable, CD4 count >400, no development of AIDS Thomas E. Starzl Transplantation Institute

  18. Transplantation in HIV+ Recipients Hahnemann (Continued) Acute Rejection - 22% Subclinical Rejection - 29% Recurrent HIVAN - 7.5% Thomas E. Starzl Transplantation Institute

  19. Transplantation in HIV+ Recipients Stock – UCSF N – 14 Kidney – 10 Liver - 4 Thomas E. Starzl Transplantation Institute

  20. Transplantation in HIV+ Recipients UCSF (Continued) Kidney – 100% patient/graft survival Acute Rejection – 56% SRR – 30% Liver – 75% patient survival (One death to recurrent HCV) No rejection Thomas E. Starzl Transplantation Institute

  21. Transplantation in HIV+ Recipients Hirose – UCSF 15 kidney recipients – 67% incidence of acute rejection, most with SRR Thomas E. Starzl Transplantation Institute

  22. Transplantation in HIV+ Recipients Impact of Protease Inhibitors • Markedly reduced calcineurin inhibitor requirements Thomas E. Starzl Transplantation Institute

  23. Transplantation in HIV+ Recipients Pittsburgh N – 10 1 – PreHAART era, cyclo-based – deceased donor 4 – HAART era, TAC-based – deceased donors 4 – HAART era, Campath/TAC Monotherapy – living donors 1 – HAART era, Campath/TAC monotherapy – deceased donor Thomas E. Starzl Transplantation Institute

  24. Transplantation in HIV+ Recipients Pittsburgh (Continued) Conventional Cyclo/TAC 100% one-year patient/graft survival but Currently 80% patient/20% graft survival (4 graft losses 3-8 years, 60% noncompliance) ACR – 80% (4/5) No AIDS, all viral loads undetectable Thomas E. Starzl Transplantation Institute

  25. Transplantation in HIV+ Recipients Pittsburgh (Continued) Campath/TAC Monotherapy – 100% patient/graft survival Living donor – 0% ACR, all on spaced weaning 1 patient also had PAK Viral loads undetectable, CD4 counts initially low Deceased donor - noncompliant Thomas E. Starzl Transplantation Institute

  26. Campath Pretreatment38 y.o. Live Donor Kidney Graft Thomas E. Starzl Transplantation Institute

  27. Campath PretreatmentPancreas after Live Donor Kidney Thomas E. Starzl Transplantation Institute

  28. Transplantation in HIV+ Recipients SRTR – Kidney Transplantation 1987 – 2004 - 178 1987 – 1996 - 38 1996 – 2004 - 140 Thomas E. Starzl Transplantation Institute

  29. Transplantation in HIV+ Recipients SRTR (Continued) One Year Pt. SurvivalGraft Survival PreHAART 93% 75% HIV- 93% 82% HAART 92% 84% HIV- 94% 88% Thomas E. Starzl Transplantation Institute

  30. Transplantation in HIV+ Recipients Multicenter NIH Trial In Progress Thomas E. Starzl Transplantation Institute

  31. Transplantation in HIV+ Recipients • In the pre-HAART era, transplantation was uncommon, although the results with kidney transplantation were reasonable. • HAART has changed the natural history of HIV, and has led to an increased interest in transplantation. • A number of single centers have achieved reasonable outcomes after kidney transplantation. • Acute rejection may be more common in HIV+ recipients than HIV- recipients. Thomas E. Starzl Transplantation Institute

  32. Transplantation in HIV+ Recipients • The interaction between protease inhibitors and calcineurin inhibitors is important. • Preconditioning with Campath followed by tacrolimus monotherapy may be a reasonable approach to immunosuppressive management in HIV+ recipients. • The current NIH-sponsored trial should provide more information about outcomes in HIV+ patients undergoing transplantation. Thomas E. Starzl Transplantation Institute