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. 2005Fabrizi et al. 2005Gentil et al. 1999Bruchfeld 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. 2011

Kumar MS. ATC 2008Stock et al 2010Touzot 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 age 52 (41-61) 54 (48-59) 46 (41-52) 50 (45-56) <0.001

Male (%) 60.2 73.2 77.4 81.6 <0.001Race (%)African AmericanCaucasianLatinoOther

25.254.414.16.1

51.233.111.24.5

72.818.16.72.3

79.613.65.42.4

<0.001

Cause of ESRD Diabetes Hypertension Glomerular disease

26.724.818.7

29.936.811

10.637.68.5

13.642.25.4

<0.001

Pretransplant dialysis 82.4 90.5 96.1 96.6 <0.001

Years on dialysis 2.7 (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 list 469 (167-996) 424 (147-932) 517(177-1218)

404 (108-875)

<0.001

PRA ≥30% 14.5 14.4 16.7 10.9 0.30Pretransplant diabetes 32.8 39.9 16.7 17.7 <0.001

Recipient Characteristics

HIV-/HCV-n=117,791

HCV+n=5605

HIV+n=492

HIV+/HCV+n=147

p value

Donor CharacteristicsDeceased donor 60.3 76.7 70.9 86.4 <0.001Expanded criteria donor 18.4 14.5 10.8 10.2 <0.001HCV+ donor 0.3 28.3 0.6 48.3 <0.001Median CIT (hours) 12 (2-20) 16 (8-23) 13 (2-22) 17 (11-24) 0.001Delayed graft function 16.1 23.5 31.3 38.8 <0.001

Immunosuppression

Tacrolimus 78.2 76.7 73.8 55.8 <0.001

Lyphodepleting induction

52.8 51 37.4 28.6 <0.001

Nondepleting induction 24 24.4 35.2 27.2 <0.001

Transplant Characteristics

Patient Survival Stratified by Serostatus

Cox Regression Models: Patient DeathHR P value 95% CI

HIV-/HCV- REF

HCV+ 1.44 <0.001 1.33-1.56

HIV+ 0.90 0.53 0.66-1.24

HIV+/HCV+ 2.26 <0.001 1.45-3.52

Age 40-60 1.91 <0.001 1.79-2.03

Age >60 3.49 <0.001 3.27-3.73

Male 0.93 0.001 0.90-0.97

African American 1.00 0.99 0.96-1.04

Pretransplant Diabetes 1.66 <0.001 1.61-1.72

Pretransplant Dialysis 1.62 <0.001 1.52-1.73

Years on Dialysis 1.04 <0.001 1.03-1.04

Deceased donor 1.33 <0.001 1.27-1.39

HCV+ donor 1.97 <0.001 1.54-2.53

Lymphodepleting induction REF

Non-depleting induction 1.13 <0.001 1.09-1.17

Allograft Survival Stratified by Serostatus

Cox Regression Models: Graft LossHR P value 95% CI

HIV-/HCV- REFHCV+ 1.43 <0.001 1.31-1.56HIV+ 0.60 0.01 0.40-0.88HIV+/HCV+ 2.59 <0.001 1.60-4.19Age 40-60 0.82 <0.001 0.78-0.88Age >60 1.09 0.002 1.03-1.16Male 0.94 0.006 0.91-0.98African American 1.27 <0.001 1.22-1.32Pretransplant Diabetes 1.34 <0.001 1.28-1.39Pretransplant Dialysis 1.60 <0.001 1.48-1.72PRA>30% 0.99 0.78 0.94-1.05Deceased donor 1.42 <0.001 1.34-1.50HCV+ donor 1.70 0.001 1.25-2.32ECD donor 1.41 <0.001 1.34-1.48Acute Rejection 1.86 0.001 1.77-1.95Non-depleting induction 1.16 <0.001 1.11-1.21

HCV ?/HIV?=89,780HCV+/HIV?=3690HIV+/HCV?=23

Demographics similar to known groupsPatient and allograft survival not significantly different from known serostatus patients

Multivariable models for death compared

Known Serostatus Cohort Known + Unknown Serostatus Cohort

variable HR* p value 95% CI HR* p value 95% CI

HIV-/HCV- REF REF

HCV+ 1.44 <0.001 1.33-1.56 1.44 <0.001 1.36-1.53

HIV+ 0.90 0.53 0.66-1.24 0.77 0.11 0.56-1.06

HIV+/HCV+ 2.26 <0.001 1.45-3.52 1.87 0.005 1.20-2.90

*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

variable HR* p value 95% CI HR* p value 95% CI

HIV-/HCV- REF REF

HCV+ 1.43 <0.001 1.31-1.56 1.42 <0.001 1.33-1.52

HIV+ 0.60 0.01 0.40-0.88 0.55 0.003 0.37-0.81

HIV+/HCV+ 2.59 <0.001 1.60-4.19 2.22 0.001 1.38-3.58

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

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 045008

Patient Survival – Known versus Unknown Serostatus

HCV+ v. HCV+/HIV?

LR=0.15HR 0.94, 95% CI 0.86-1.02

HIV+ v. HIV+/HCV?

LR=0.25HR 1.83, 95% CI 0.64-5.13

HIV-/HCV- v. HCV?/HIV?

LR<0.001HR 1.06 95% CI 1.04-1.09

Allograft Survival – Known versus Unknown Serostatus

HIV-/HCV- v. HCV?/HIV?

LR<0.001HR 1.02, 95% CI 1.01-1.02

HCV+ v. HCV+/HIV?

LR=0.21HR 1.01, 95% CI 0.99-1.03

HIV+ v. HIV+/HCV?

LR=0.21HR=1.12, 95% CI 0.93-1.34