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

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

3. Thomas E. Starzl Transplantation Institute 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%)

4. Thomas E. Starzl Transplantation Institute 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.

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

6. Thomas E. Starzl Transplantation Institute 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.

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

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

9. Thomas E. Starzl Transplantation Institute Transplantation in HIV+ Recipients 1/3/5 Year Survival Patient Graft 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

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

11. Thomas E. Starzl Transplantation Institute 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

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

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

14. Thomas E. Starzl Transplantation Institute 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

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

16. Thomas E. Starzl Transplantation Institute Transplantation in HIV+ Recipients Inclusion Criteria Undetectable viral load (< 400 or <50 copies/ml) CD4 count >200 cells/mm 3

17. Thomas E. Starzl Transplantation Institute 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

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

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

20. Thomas E. Starzl Transplantation Institute 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

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

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

23. Thomas E. Starzl Transplantation Institute 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

24. Thomas E. Starzl Transplantation Institute 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

25. Thomas E. Starzl Transplantation Institute 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

26. Thomas E. Starzl Transplantation Institute Campath Pretreatment 38 y.o. Live Donor Kidney Graft

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

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

29. Thomas E. Starzl Transplantation Institute Transplantation in HIV+ Recipients SRTR (Continued) One Year Pt. Survival Graft Survival PreHAART93%75% HIV-93%82% HAART92%84% HIV-94%88%

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

31. Thomas E. Starzl Transplantation Institute Transplantation in HIV+ Recipients 1.In the pre-HAART era, transplantation was uncommon, although the results with kidney transplantation were reasonable. 2.HAART has changed the natural history of HIV, and has led to an increased interest in transplantation. 3.A number of single centers have achieved reasonable outcomes after kidney transplantation. 4.Acute rejection may be more common in HIV+ recipients than HIV- recipients.

32. Thomas E. Starzl Transplantation Institute Transplantation in HIV+ Recipients 5.The interaction between protease inhibitors and calcineurin inhibitors is important. 6.Preconditioning with Campath followed by tacrolimus monotherapy may be a reasonable approach to immunosuppressive management in HIV+ recipients. 7.The current NIH-sponsored trial should provide more information about outcomes in HIV+ patients undergoing transplantation.