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

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 Fabrizi et al Gentil et al Bruchfeld et al. 2004

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 Kumar MS. ATC 2008 Stock et al 2010 Touzot et al 2010 Mazuecos et al 2011.

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+).

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

Patient Cohort Assembly

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 (%) <0.001 Race (%) African American Caucasian Latino Other <0.001 Cause of ESRD Diabetes Hypertension Glomerular disease <0.001 Pretransplant dialysis <0.001 Years on dialysis2.7 ( )3.2 ( )5.5 (2.8-8)5 ( )<0.001 Days on wait list469 ( )424 ( ) 517( ) 404 ( ) <0.001 PRA ≥30% Pretransplant diabetes <0.001 Recipient Characteristics

HIV-/HCV- n=117,791 HCV+ n=5605 HIV+ n=492 HIV+/HCV+ n=147 p value Donor Characteristics Deceased donor <0.001 Expanded criteria donor <0.001 HCV+ donor <0.001 Median CIT (hours) 12 (2-20)16 (8-23)13 (2-22)17 (11-24) Delayed graft function <0.001 Immunosuppression Tacrolimus <0.001 Lyphodepleting induction <0.001 Nondepleting induction <0.001 Transplant Characteristics

Patient Survival Stratified by Serostatus

Cox Regression Models: Patient Death HRP value95% CI HIV-/HCV-REF HCV+1.44< HIV HIV+/HCV+2.26< Age < Age >603.49< Male African American Pretransplant Diabetes1.66< Pretransplant Dialysis1.62< Years on Dialysis1.04< Deceased donor1.33< HCV+ donor1.97< Lymphodepleting inductionREF Non-depleting induction1.13<

Allograft Survival Stratified by Serostatus

Cox Regression Models: Graft Loss HRP value95% CI HIV-/HCV-REF HCV+1.43< HIV HIV+/HCV+2.59< Age < Age > Male African American1.27< Pretransplant Diabetes1.34< Pretransplant Dialysis1.60< PRA>30% Deceased donor1.42< HCV+ donor ECD donor1.41< Acute Rejection Non-depleting induction1.16<

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

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< < HIV HIV+/HCV+2.26< *adjusting for age, sex, race, pretransplant DM, dialysis, time on dialysis, donor type, transplant year, HCV+ donor, maintenance and induction immunosuppression

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< < HIV HIV+/HCV+2.59< *adjusting for age, sex, race, pretransplant DM, dialysis, PRA>30%, donor type, diabetic donor, HCV+ donor, acute rejection, transplant year, maintenance and induction immunosuppression

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

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

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

Patient Survival – Known versus Unknown Serostatus HCV+ v. HCV+/HIV? LR=0.15 HR 0.94, 95% CI HIV+ v. HIV+/HCV? LR=0.25 HR 1.83, 95% CI HIV-/HCV- v. HCV?/HIV? LR<0.001 HR % CI

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