LUNG TRANSPLANTATION Pediatric Recipients ISHLT 2006 J Heart Lung Transplant 2006;25:904-911.
Transplantation in HIV+ Recipients
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Transplantation in HIV+ Recipients
Ron Shapiro, M.D.THOMAS E. STARZL TRANSPLANTATION INSTITUTE
UNIVERSITY OF PITTSBURGH
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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.
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
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%)
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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.
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Minnesota – 1990
N – 21, 5 local and 16 from literature
Kidney – 11
Liver – 10
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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.
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Liver
90% mortality, 40% death from AIDS
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
USRDS – 1987-1997
• 32 HIV+ patients underwent renal transplantation
• 0.05% of transplants
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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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Acute Rejection
• HIV+ 50%
• HIV- 48.4%
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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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
HAART – 1996
Highly active antiretroviral therapy
HIV+ ≠ AIDS
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
If HIV+ ≠ AIDS
Why deny transplantation to HIV+ patients?
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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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
HIV+ Patients on Dialysis
Survival – USRDS
1 Year 2 Years
58% 41%
32.7% One Year Mortality
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Inclusion Criteria
Undetectable viral load (< 400 or
<50 copies/ml)
CD4 count >200 cells/mm3
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Hahnemann (Continued)
Acute Rejection - 22%
Subclinical Rejection - 29%
Recurrent HIVAN - 7.5%
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Stock – UCSF
N – 14
Kidney – 10
Liver - 4
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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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Hirose – UCSF
15 kidney recipients –
67% incidence of acute rejection, most
with SRR
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Impact of Protease Inhibitors
• Markedly reduced calcineurin inhibitor requirements
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
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
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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
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Thomas E. Starzl Transplantation Institute
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
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Thomas E. Starzl Transplantation Institute
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
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
SRTR – Kidney Transplantation
1987 – 2004 - 178
1987 – 1996 - 38
1996 – 2004 - 140
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
SRTR (Continued)One Year
Pt. Survival Graft SurvivalPreHAART 93% 75%HIV- 93% 82%HAART 92% 84%HIV- 94% 88%
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Thomas E. Starzl Transplantation Institute
Transplantation in HIV+ Recipients
Multicenter NIH Trial
In Progress
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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.
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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.