transplantation in hiv+ recipients

Transplantation in HIV+ Recipients

Ron Shapiro, M.D.THOMAS E. STARZL TRANSPLANTATION INSTITUTE

UNIVERSITY OF PITTSBURGH

Thomas E. Starzl Transplantation Institute


Prior to 1996 -

• HIV+ = AIDS

• Transplantation formally contraindicated

• Median survival for HIV+ patients on dialysis – 10 months.



Tzakis – Pittsburgh Experience 1981-1988N – 25

Pediatric – 1011 - Infected Pretransplantation14 - Infected Peritransplantation

Patients SurvivorsLiver 15 7(43%)Kidney 5 4(80%)Heart 5 2(40%)



Pediatric – 70% Survival

One Death from AIDS

Adult – 40% Survival

5 Deaths from AIDS

However, survival not statistically worse than in HIV- recipients.



Minnesota – 1990

N – 21, 5 local and 16 from literature

Kidney – 11

Liver – 10



Kidney

3 – Died of AIDS

6/8 (75%) – Normal graft function at 2-1/2 years and no HIV-related complications.



Liver

90% mortality, 40% death from AIDS



USRDS – 1987-1997

• 32 HIV+ patients underwent renal transplantation

• 0.05% of transplants



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



Acute Rejection

• HIV+ 50%

• HIV- 48.4%



Cyclosporine → Lower Incidence of AIDS

31% versus 90% at 5 years

Inhibition of HIV Replication

Binding to HIV -1 Gag protein



HAART – 1996

Highly active antiretroviral therapy

HIV+ ≠ AIDS



If HIV+ ≠ AIDS

Why deny transplantation to HIV+ patients?



HIV-Associated Nephropathy (HIVAN) –

Third leading cause of ESRD in African-Americans 20-64 years of age

HIV+/HCV+ → accelerated progression to ESLD



HIV+ Patients on Dialysis

Survival – USRDS

1 Year 2 Years

58% 41%

32.7% One Year Mortality



Inclusion Criteria

Undetectable viral load (< 400 or

<50 copies/ml)

CD4 count >200 cells/mm3



Kumar – Hahnemann

N- 40 2/01-1/04 (97% African-American)

Survival

1 Year 2 Years

Patient 85% 82%

Graft 75% 71%

Viral load undetectable, CD4 count >400, no development of AIDS



Hahnemann (Continued)

Acute Rejection - 22%

Subclinical Rejection - 29%

Recurrent HIVAN - 7.5%



Stock – UCSF

N – 14

Kidney – 10

Liver - 4



UCSF (Continued)Kidney – 100% patient/graft survival

Acute Rejection – 56%SRR – 30%

Liver – 75% patient survival(One death to recurrent HCV)

No rejection



Hirose – UCSF

15 kidney recipients –

67% incidence of acute rejection, most

with SRR



Impact of Protease Inhibitors

• Markedly reduced calcineurin inhibitor requirements



Pittsburgh

N – 101 – PreHAART era, cyclo-based – deceased donor4 – HAART era, TAC-based – deceased donors4 – HAART era, Campath/TAC Monotherapy –

living donors1 – HAART era, Campath/TAC monotherapy –

deceased donor



Pittsburgh (Continued)Conventional Cyclo/TAC

100% one-year patient/graft survival butCurrently 80% patient/20% graft survival

(4 graft losses 3-8 years, 60% noncompliance)ACR – 80% (4/5)

No AIDS, all viral loads undetectable



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


Graft Function

0

4

8

mg

/d

l

Creatinine

Biopsy and Additional Treatment

110

1001000

11/ 03 5/ 04 11/ 04 5/ 05

Ste

roid

D

ose

mg

Steroid PO

Biopsy

Steroid Bolus

I mmunosuppression

0

10

20

ng

/m

l

0

10

20

Dose

mg

Tac. qod

Tac. qd

Tac. bid

Tac. Level

Campath Pretreatment38 y.o. Live Donor Kidney Graft


Graft Function

0

4

8

Cre

at.

mg

/d

l

0

250

500

Lip

ase Creatinine

Lipase

Biopsy and Additional Treatment

110

1001000

9/ 03 3/ 04 9/ 04 3/ 05

Dose

mg Steroid PO

BiopsyPancreas TXCampathSteroid Bolus

I mmunosuppression

0

10

20

ng

/m

l

0

0.2

0.4

0.6

Dose

mg

Tac. Dose

Tac. Level

Campath PretreatmentPancreas after Live Donor Kidney



SRTR – Kidney Transplantation

1987 – 2004 - 178

1987 – 1996 - 38

1996 – 2004 - 140



SRTR (Continued)One Year

Pt. Survival Graft SurvivalPreHAART 93% 75%HIV- 93% 82%HAART 92% 84%HIV- 94% 88%



Multicenter NIH Trial

In Progress



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.



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.

transplantation in hiv+ recipients

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