hiv-related predictors and outcomes in 275 liver and/or kidney transplant recipients beatty g 1,...
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HIV-Related Predictors and Outcomes in 275 Liver and/or Kidney
Transplant Recipients
Beatty G1, Barin B2, Fox L3, Odim J3, Huprikar S4, Wong M5, Diego J6, Blumberg E7, Simon D8, Light J9, Yin M10, Davis C11, Jayaweera D12, Hardy D13, Ragni M14, Johnson L15, Subramanian A16, Stosor T17, Brayman K18, Pursell K19, Zhang R20, Lyon G21, Taege A22, Feinberg J23, Weikert B24, Stock P1, Roland M1.
1University of California, San Francisco; 2EMMES Corp.; 3National Institutes of Health; 4Mt. Sinai Medical Center; 5Beth Israel Deaconess Medical Center; 6University of Miami; 7University Pennsylvania; 8Rush University; 9Washington Hospital Center; 10Columbia University; 11University of Maryland; 12University of Miami; 13Cedars-Sinai Medical Center; 14University of Pittsburgh; 15Georgetown University; 16Johns Hopkins University; 17Northwestern University; 18University of Virginia; 19University of Chicago; 20Tulane University; 21Emory University; 22Cleveland Clinic; 23University of Cincinnati; 24Drexel University.
On behalf of the investigators of Solid Organ Transplantation in HIV: Multi-Site Study Funded by the National Institute of Allergy and Infectious Diseases (AI052748)
Sponsored by the University of California, San Francisco
6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention
George Beatty, MD, MPHUCSF Positive Health Program at SFGH
University of California San Francisco
I have no financial relationships to disclose within the past 12 months relevant to my presentation.
My presentation does not include discussion of off-label or investigational use.
I do not intend to reference unlabeled/unapproved uses of drugs or products in my presentation.
Rationale
Historically, HIV considered a contraindication to organ transplantation
End-organ disease emerging as major cause of morbidity/mortality in HIV1
Limited experience with liver and kidney transplants in ART era has been encouraging, but optimal selection criteria and predictors of outcome remain undefined2
2Roland, et al. Am J Trnsplnt 2008;8:355-365; Stock, et al. Am J Trnsplnt 2009; 9(2): 197; Terrault, et al. Liver Trnsplnt 2006; 12:801-807
1Mocroft, et al. AIDS 2005 19:2117-2125; Ragni, et al. Liver Transpl 2002; 11:1425-1430; Palella, et al. NEJM 1998: 338:853-860; others.
Study Aim
We describe rates and predictors of– Patient survival– AIDS-related opportunistic infections (OI) and
neoplasms– Other serious infections with hospitalization (SI)
125 liver transplant recipients 150 kidney transplant recipients
Subjects
Standard transplant criteria CD4 > 200 for kidney & 100 for liver recipients Undetectable HIV RNA
– or expected control post-transplant for
liver recipients who could not tolerate
antiretrovirals Treated OIs except visceral KS, PML, chronic
cryptosporidiosis
Predictors of Post-Transplant Mortality
Demographics: age, sex, race HIV factors: CD4 at nadir, study enrollment, and
pre-TX; viral load at enrollment and pre-TX; OI history
Transplant factors: HCV, BMI at enrollment and pre-TX, rejection, dual organ TX1 , MELD score pre-TX1 , initial thymoglobulin use2
Donor factors: HCV, age, marginal donor1 Proportional hazards models 1 Liver
2 Kidney
Patient Survival
Median years follow-up post-transplant– Kidney: 2.3 [1.0, 3.7] – Liver: 2.7 [1.8, 4.0]
1 & 3 year patient survival– Kidney: 95% (90%, 98%) & 91% (84%, 95%) – Liver: 80% (72%, 86%) & 67% (56%, 75%)
Factors Associated with Mortality: Kidney Recipients
1. HCV (HR 3.17; CI 1.10, 9.09; p=0.03)
2. Age (HR 1.06; CI 1.01, 1.11; p=0.03)
Marginally initial thymoglobulin use(HR 2.63; CI 0.94, 7.31; p=0.06)
Factors Associated with Mortality: Liver Recipients
1. Dual organ TX (HR 4.86; 1.93, 12.2; p=0.0008)
2. Pre-TX BMI <21 (HR 2.74; 1.25, 5.98; p=0.01)
3. Donor age >40 (HR 2.23; 1.07, 4.64; p=0.03)
Marginally HCV (HR 2.47; 0.95, 6.44; p=0.06)
Marginally detectable enrollment viral load (HR 2.07; 0.89, 4.81; p=0.09)
Impact of Transplant on Mortality
This analysis includes BOTH recipients and waitlisted, eligible subjects
Add transplant status as a variable to proportional hazards models
Same baseline and pre-tx factors (no donor) CD4, viral load and MELD as time-dependent
covariates
Transplant Associated Survival Benefit
Liver Yes MELD ≥15 HR: 0.09; 0.05, 0.16; p<0.0001
No…? MELD < 15
HR: 0.71; 0.27, 1.85; p=0.48
Kidney No… ?
HR: 0.67; 0.31, 1.45; p=0.31
• Small sample size/event numbers limit power for low MELD & kidney
• Also evaluating quality of life
Opportunistic Infections
Pre-transplant52 (19%) had 90 OIs
– 30 PCP– 8 CMV– 7 MAC– 3 KS
Post-transplant 13
– 4 KS (all cutaneous)
– 2 PCP– 1 cryptosporidiosis– 6 Candida (5 esophageal, 1 bronch.)
Most Common OIs
No recurrences in patients with OI history
No survival differences based on OI history
There were many serious infections
77 (51%) kidney recipients had 212 – 64% bacterial, 8% fungal, 10% viral, 17% culture
negative/not done– 23% genitourinary, 20% respiratory, 19% blood
70 (56%) liver recipients had 243– 71% bacterial, 7% fungal, 5% viral, 1% protozoal,
17% culture negative/not done– 17% respiratory, 17% blood, 12% genitourinary
Factors Associated with Initial Serious Infection
Kidney
1. HCV (HR 2.27; 1.33, 3.87; p = 0.003)
2. Initial thymo (HR 2.10; 1.25, 3.53; p = 0.01)
3. Nadir CD4 (HR 0.93; 0.87, 1.00; p=0.048)
Liver
4. HCV (HR 2.34; 1.13, 4.83; p = 0.02)
5. *CD4 (HR 0.88; 0.80, 0.98; p = 0.02)
6. White race (HR 0.49; 0.28, 0.85; p = 0.01)
* Time dependent covariate
Conclusions
1. Kidney survival is excellent 2. Liver transplant in high MELD confers survival benefit3. HIV factors are not associated with mortality or the
development of OI4. No recurrent OIs in those with history of select OI5. Serious infections requiring/during hospitalization
were common 6. Baseline factors (BMI & need for dual organ
transplant) may influence recommendations re: selection criteria in liver candidates
Preliminary data; analyses currently being updated for publication
University of California, SFPeter Stock, MD, PhD (PI)Michelle Roland, MD (Co-PI)
Cedars-Sinai, LAFred Poordad, MD (PI)Nicholas Nissen, MD (Co-PI)
University of MarylandRobert Redfield, MD (PI)Stephen Bartlett, MD (Co-PI)
DrexelAnil Kumar, MD (PI – Kidney)Burkhardt Ringe, MD (PI – Liver)Jeffrey Jacobson, MD (Co-PI)
University of VirginiaKenneth Brayman, MD, PhD (PI)
University of PennsylvaniaKim Olthoff, MD (PI)Emily Blumberg, MD (Co-PI)
University of PittsburghMargaret Ragni, MD, MPH (PI)Ron Shaprio, MD (Co-PI)
Washington Hospital CenterJimmy Light , MD(PI)
Mt. SinaiBarbara Murphy, MD(PI)
Thomas Schiano, MD (Co-PI)
Columbia UniversityLorna Dove, MD (PI)Jean Emond, MD (Co-PI)
Georgetown UniversityLynt Johnson, MD (PI)
University of ChicagoJ. Michael Millis, MD (PI)
University of CincinnatiKenneth Sherman, MD, PhD (PI)Rita Alloway, PharmD (Co-PI)
University of MiamiJorge Diego, MD (PI – K)Andreas Tzakis, MD, PhD (PI – L)David Roth, MD (Co-PI – K)
Beth Israel DeaconessDouglas Hanto, MD, PhD (PI)Michael Wong, MD (Co-PI)
Emory UniversityTom Pearson, MD, DPhil (PI)
Rush UniversityDavid Simon, MD, PhD (PI)
Tulane UniversityDouglas Slakey, MD (PI)
Cleveland ClinicJohn Fung, MD, PhD (PI)
Johns HopkinsAruna Subramanian, MD (PI)
Northwestern
Tina Stosor, MD (PI)Richard Green, MD (Co-PI)
We’d like to acknowledge the participating transplant centers and their study investigators and study coordinators, too many to name. We also thank the study participants and donors and donor families!