1. Superior outcomes in HIV-positive kidney transplant patients compared to HCV-infected or HIV/HCV co-infected recipients Deirdre Sawinski MD, Kimberly A Forde MD, Kevin Eddinger, Emily Blumberg MD, Pablo Tebas MD, Peter L Abt MD, and Roy D Bloom MD #NephJC

2. HCV and Renal Transplant Prevalence of 6-40% Most patients are viremic at time of transplant Transplantation offers a survival benefit compared to dialysis Patient and allograft outcomes are inferior to those in HCV- patients Bloom et al. 2005 Fabrizi et al. 2005 Gentil et al. 1999 Bruchfeld et al. 2004

3. HIV and Renal Transplant Required to be aviremic at transplant Transplantation offers a survival compared to dialysis Patient and allograft outcomes have been excellent with 2-3 year follow up Experience with HCV/HIV- coinfected patients is limited but outcomes are not as good as in HIV+ recipients alone Martina et al. 2011 Kumar MS. ATC 2008 Stock et al 2010 Touzot et al 2010 Mazuecos et al 2011.

4. Specific Aims Aim 1: To confirm and extend published reports of good post-transplant outcomes for HIV+ renal transplant recipients using a larger cohort Aim 2: To compare patient and kidney outcomes in patients who are HIV+ versus HCV+ or co-infected (HIV+/HCV+).

5. Methods Data source: UNOS Standard Transplant Analysis and Research (STAR) file All waitlist registrations and transplants performed 10/1/87 – 12/31/13 with follow up through 3/15/14. Patients grouped by HIV and HCV serostatus

6. Patient Cohort Assembly

7. HIV-/HCV- n=117,791 HCV+ n=5605 HIV+ n=492 HIV+/HCV+ n=147 p value Median age52 (41-61)54 (48-59)46 (41-52)50 (45-56)<0.001 Male (%) 60.273.277.481.6<0.001 Race (%) African American Caucasian Latino Other 25.2 54.4 14.1 6.1 51.2 33.1 11.2 4.5 72.8 18.1 6.7 2.3 79.6 13.6 5.4 2.4 <0.001 Cause of ESRD Diabetes Hypertension Glomerular disease 26.7 24.8 18.7 29.9 36.8 11 10.6 37.6 8.5 13.6 42.2 5.4 <0.001 Pretransplant dialysis82.490.596.196.6<0.001 Years on dialysis2.7 (1.3-4.5)3.2 (1.6-5.4)5.5 (2.8-8)5 (3.0-7.6)<0.001 Days on wait list469 (167-996)424 (147-932) 517(177- 1218) 404 (108- 875) <0.001 PRA ≥30%14.514.416.710.90.30 Pretransplant diabetes32.839.916.717.7<0.001 Recipient Characteristics

8. HIV-/HCV- n=117,791 HCV+ n=5605 HIV+ n=492 HIV+/HCV+ n=147 p value Donor Characteristics Deceased donor 60.376.770.986.4 <0.001 Expanded criteria donor 18.414.510.810.2 <0.001 HCV+ donor 0.328.30.648.3 <0.001 Median CIT (hours) 12 (2-20)16 (8-23)13 (2-22)17 (11-24) 0.001 Delayed graft function 16.123.531.338.8 <0.001 Immunosuppression Tacrolimus78.276.773.855.8<0.001 Lyphodepleting induction52.85137.428.6<0.001 Nondepleting induction2424.435.227.2<0.001 Transplant Characteristics

9. Patient Survival Stratified by Serostatus

10. Cox Regression Models: Patient Death HRP value95% CI HIV-/HCV-REF HCV+1.44<0.0011.33-1.56 HIV+0.900.530.66-1.24 HIV+/HCV+2.26<0.0011.45-3.52 Age 40-601.91<0.0011.79-2.03 Age >603.49<0.0013.27-3.73 Male0.930.0010.90-0.97 African American1.000.990.96-1.04 Pretransplant Diabetes1.66<0.0011.61-1.72 Pretransplant Dialysis1.62<0.0011.52-1.73 Years on Dialysis1.04<0.0011.03-1.04 Deceased donor1.33<0.0011.27-1.39 HCV+ donor1.97<0.0011.54-2.53 Lymphodepleting inductionREF Non-depleting induction1.13<0.0011.09-1.17

11. Allograft Survival Stratified by Serostatus

12. Cox Regression Models: Graft Loss HRP value95% CI HIV-/HCV-REF HCV+1.43<0.0011.31-1.56 HIV+0.600.010.40-0.88 HIV+/HCV+2.59<0.0011.60-4.19 Age 40-600.82<0.0010.78-0.88 Age >601.090.0021.03-1.16 Male0.940.0060.91-0.98 African American1.27<0.0011.22-1.32 Pretransplant Diabetes1.34<0.0011.28-1.39 Pretransplant Dialysis1.60<0.0011.48-1.72 PRA>30%0.990.780.94-1.05 Deceased donor1.42<0.0011.34-1.50 HCV+ donor1.700.0011.25-2.32 ECD donor1.41<0.0011.34-1.48 Acute Rejection1.860.0011.77-1.95 Non-depleting induction1.16<0.0011.11-1.21

13. HCV ?/HIV?=89,780 HCV+/HIV?=3690 HIV+/HCV?=23 Demographics similar to known groups Patient and allograft survival not significantly different from known serostatus patients

16. Multivariable models for death compared Known Serostatus Cohort Known + Unknown Serostatus Cohort variableHR*p value95% CI HR*p value95% CI HIV-/HCV-REF HCV+1.44<0.0011.33-1.561.44<0.0011.36-1.53 HIV+0.900.530.66-1.240.770.110.56-1.06 HIV+/HCV+2.26<0.0011.45-3.521.870.0051.20-2.90 *adjusting for age, sex, race, pretransplant DM, dialysis, time on dialysis, donor type, transplant year, HCV+ donor, maintenance and induction immunosuppression

17. Multivariable models for allograft loss compared Known Serostatus Cohort Known + Unknown Serostatus Cohorts variableHR*p value95% CIHR*p value95% CI HIV-/HCV-REF HCV+1.43<0.0011.31-1.561.42<0.0011.33-1.52 HIV+0.600.010.40-0.880.550.0030.37-0.81 HIV+/HCV+2.59<0.0011.60-4.192.220.0011.38-3.58 *adjusting for age, sex, race, pretransplant DM, dialysis, PRA>30%, donor type, diabetic donor, HCV+ donor, acute rejection, transplant year, maintenance and induction immunosuppression

18. Summary As previously reported, HIV+ kidney transplant recipients have patient and allograft survival similar to uninfected recipients Patient and allograft survival is superior for HIV+ compared to HCV+ kidney recipients Co-infected kidney recipients (HIV+/HCV+) have the worst patient and allograft outcomes

19. Conclusions Centers should be more selective in transplanting HCV+ kidney candidates. Controlled HIV infection should not be perceived as a barrier to kidney transplant Control of HCV with treatment should be a priority for both HCV+ and HIV+/HCV+ recipients

20. Acknowledgments Co-Investigators – Kevin Eddinger – Kimberly Forde, MD – Peter Abt, MD – Roy Bloom, MD – Emily Blumberg, MD – Pablo Tebas, MD Support Penn Center for AIDS Research (CFAR) Pilot Grant P30 AI 045008

21. Patient Survival – Known versus Unknown Serostatus HCV+ v. HCV+/HIV? LR=0.15 HR 0.94, 95% CI 0.86-1.02 HIV+ v. HIV+/HCV? LR=0.25 HR 1.83, 95% CI 0.64-5.13 HIV-/HCV- v. HCV?/HIV? LR<0.001 HR 1.06 95% CI 1.04-1.09

22. Allograft Survival – Known versus Unknown Serostatus HIV-/HCV- v. HCV?/HIV? LR<0.001 HR 1.02, 95% CI 1.01-1.02 HCV+ v. HCV+/HIV? LR=0.21 HR 1.01, 95% CI 0.99-1.03 HIV+ v. HIV+/HCV? LR=0.21 HR=1.12, 95% CI 0.93-1.34