Clinical trial NCT00074386: Kidney and Liver Transplantation in People With HIV
Official title: Solid Organ Transplantation in HIV: Multi-Site Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Kidney Disease
Liver Disease
Keywords: HIV
Transplant
Liver
Kidney
Organ
Treatment Experienced
Kidney Transplant
Liver Transplant
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2003-12-15
Enrollment: 275
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: HIV-positive patients who undergo kidney or liver transplantation.

Brief summary: With improved anti-HIV drug therapy, HIV infected patients are now living longer. These patients are at risk for liver and kidney failure and may need organ transplants. However, little is know about the safety and effectiveness of organ transplants in patients with HIV. This study will evaluate organ transplantation in HIV infected patients undergoing liver and kidney transplants.

Detailed description: HIV infected people are at significant risk for end stage organ disease. Prior to the advent of highly active antiretroviral therapy (HAART), these people were often not considered transplant candidates based on concern about potential adverse effects of immunosuppressive drugs on HIV disease progression. However, with the use of HAART, HIV infected people have experienced significant improvements in morbidity and mortality. HIV infected people with end stage kidney and liver disease are now potential candidates for transplantation, yet patients and clinicians lack the necessary data to determine the safety and efficacy of transplantation and immunosuppression in this group. This lack of conclusive data has led to continued denial of care by many transplant centers and third party payers, resulting in frustration and confusion for both patients and their health care providers.

This study will evaluate the safety and efficacy of solid organ transplantation in people with HIV infection by following a prospective, multi-center cohort of HIV infected people who undergo kidney or liver transplantation. The long-term goals are: 1) to provide patients and clinicians with information regarding the HIV-specific risks of transplantation; 2) to provide clinicians with information necessary to manage immunosuppressive and HAART medications together; and 3) to understand underlying basic science mechanisms that explain patient outcomes so that clinical management can be adjusted to improve outcomes.

Approximately 150 kidney and 125 liver transplant patients will be enrolled in this study over a 3-year period at medical research centers throughout the United States. Participants will be enrolled in the study for five years from the day of the transplant.

Eligibility criteria: Inclusion Criteria for All Participants:

* HIV infection
* Undetectable HIV viral load
* Meet all eligibility requirements for a transplant (same requirements that HIV uninfected patients must meet)
* Willing to take medication to prevent certain infections
* Willing to undergo frequent monitoring, including liver biopsies, and treatment, if participant has hepatitis B or C virus infection
* Willing to submit laboratory test results within 7 days of blood draw
* Willing to notify the transplant team before changing any medications
* If participant has a history of HIV-related cancers or opportunistic infections, some additional eligibility criteria must be met.

Inclusion Criteria for Patients Undergoing Kidney Transplant:

* CD4 count greater than 200 cells/mm3. CD4 count requirement for children will be based on child's age. Participant cannot have used the drugs IL-2 or GM-CSF in order to increase the CD4 count in the 6 months prior to transplant.

Inclusion Criteria for Patients Undergoing Liver Transplant:

* CD4 count greater than 100 cells/mm3. CD4 count requirement for children will be based on child's age. Some participants with certain HIV-related diseases must have a CD4 count that is greater than 200 cells/ml for the 6 months prior to study entry.

Exclusion Criteria for All Participants:

* Pregnancy
* Significant wasting or weight loss

Primary outcomes:
measure: Subject survival
timeFrame: 5 years
measure: graft survival
timeFrame: 5 years
Secondary outcomes:
measure: Opportunistic complications
timeFrame: 5 years
measure: CD4+ T cell counts and HIV-1 RNA levels
timeFrame: 5 years
measure: viral markers and host-response (CFC and ELISPOT) to viral co-pathogens, including HBV, HCV,CMV, EBV, HHV-6, HHV-8, and HPV
timeFrame: 5 years
measure: rejection rates and markers of alloresponse
timeFrame: 5 years
measure: pharmacokinetic interactions between immunosuppressive agents and antiretrovirals
timeFrame: 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedar-Sinai Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami, Jackson Memorial Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess
state: Massachusetts
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Hospital
state: New York
city: Cincinnati
country: United States
facility: The University Hospital, Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Thomas E. Starzl Institute
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of California, San Francisco
name: Peter Stock, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Michelle Roland
role: PRINCIPAL_INVESTIGATOR
References:
citation: Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, Ragni MV, Barin B, Simon D, Olthoff KM, Johnson L, Stosor V, Jayaweera D, Fung J, Sherman KE, Subramanian A, Millis JM, Slakey D, Berg CL, Carlson L, Ferrell L, Stablein DM, Odim J, Fox L, Stock PG; Solid Organ Transplantation in HIV: Multi-Site Study Investigators. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transpl. 2012 Jun;18(6):716-26. doi: 10.1002/lt.23411.
citation: Carter JT, Melcher ML, Carlson LL, Roland ME, Stock PG. Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant. 2006 Apr;6(4):753-60. doi: 10.1111/j.1600-6143.2006.01238.x.
citation: Frassetto L, Baluom M, Jacobsen W, Christians U, Roland ME, Stock PG, Carlson L, Benet LZ. Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients. Transplantation. 2005 Jul 15;80(1):13-7. doi: 10.1097/01.tp.0000165111.09687.4e.
citation: Roland ME, Carlson LL, Frassetto LA, Stock PG. Solid organ transplantation: referral, management, and outcomes in HIV-infected patients. AIDS Read. 2006 Dec;16(12):664-8, 675-8.
citation: Roland ME, Stock PG. Liver transplantation in HIV-infected recipients. Semin Liver Dis. 2006 Aug;26(3):273-84. doi: 10.1055/s-2006-947297.
citation: Roland ME, Stock PG. Solid organ transplantation is a reality for patients with HIV infection. Curr HIV/AIDS Rep. 2006 Sep;3(3):132-8. doi: 10.1007/BF02696657.
citation: Terrault NA, Carter JT, Carlson L, Roland ME, Stock PG. Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation. Liver Transpl. 2006 May;12(5):801-7. doi: 10.1002/lt.20776.
citation: Bihl FK, Loggi E, Chisholm JV 3rd, Hewitt HS, Henry LM, Linde C, Suscovich TJ, Wong JT, Frahm N, Andreone P, Brander C. Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and "RecycleSpot". J Transl Med. 2005 May 11;3(1):20. doi: 10.1186/1479-5876-3-20.
citation: Frassetto LA, Browne M, Cheng A, Wolfe AR, Roland ME, Stock PG, Carlson L, Benet LZ. Immunosuppressant pharmacokinetics and dosing modifications in HIV-1 infected liver and kidney transplant recipients. Am J Transplant. 2007 Dec;7(12):2816-20. doi: 10.1111/j.1600-6143.2007.02007.x. Epub 2007 Oct 19.
citation: Stock PG, Roland ME. Evolving clinical strategies for transplantation in the HIV-positive recipient. Transplantation. 2007 Sep 15;84(5):563-71. doi: 10.1097/01.tp.0000279190.96029.77.
citation: Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009 Oct;5(10):582-9. doi: 10.1038/nrneph.2009.140.
citation: Subramanian A, Sulkowski M, Barin B, Stablein D, Curry M, Nissen N, Dove L, Roland M, Florman S, Blumberg E, Stosor V, Jayaweera DT, Huprikar S, Fung J, Pruett T, Stock P, Ragni M. MELD score is an important predictor of pretransplantation mortality in HIV-infected liver transplant candidates. Gastroenterology. 2010 Jan;138(1):159-64. doi: 10.1053/j.gastro.2009.09.053. Epub 2009 Sep 30.
citation: Gasser O, Bihl F, Sanghavi S, Rinaldo C, Rowe D, Hess C, Stablein D, Roland M, Stock P, Brander C. Treatment-dependent loss of polyfunctional CD8+ T-cell responses in HIV-infected kidney transplant recipients is associated with herpesvirus reactivation. Am J Transplant. 2009 Apr;9(4):794-803. doi: 10.1111/j.1600-6143.2008.02539.x.
citation: Coffin CS, Stock PG, Dove LM, Berg CL, Nissen NN, Curry MP, Ragni M, Regenstein FG, Sherman KE, Roland ME, Terrault NA. Virologic and clinical outcomes of hepatitis B virus infection in HIV-HBV coinfected transplant recipients. Am J Transplant. 2010 May;10(5):1268-75. doi: 10.1111/j.1600-6143.2010.03070.x. Epub 2010 Mar 19.
citation: Tan-Tam CC, Frassetto LA, Stock PG. Liver and kidney transplantation in HIV-infected patients. AIDS Rev. 2009 Oct-Dec;11(4):190-204.
citation: Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, Davis C, Blumberg E, Simon D, Subramanian A, Millis JM, Lyon GM, Brayman K, Slakey D, Shapiro R, Melancon J, Jacobson JM, Stosor V, Olson JL, Stablein DM, Roland ME. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med. 2010 Nov 18;363(21):2004-14. doi: 10.1056/NEJMoa1001197.
citation: Harbell J, Fung J, Nissen N, Olthoff K, Florman SS, Hanto DW, Light J, Bartlett ST, Tzakis AG, Pearson TC, Barin B, Roland ME, Stock PG; HIV-TR Investigators. Surgical complications in 275 HIV-infected liver and/or kidney transplantation recipients. Surgery. 2012 Sep;152(3):376-81. doi: 10.1016/j.surg.2012.06.012.
citation: Nissen NN, Barin B, Stock PG. Malignancy in the HIV-infected patients undergoing liver and kidney transplantation. Curr Opin Oncol. 2012 Sep;24(5):517-21. doi: 10.1097/CCO.0b013e328355e0d7.
citation: Ragni MV, Devera ME, Roland ME, Wong M, Stosor V, Sherman KE, Hardy D, Blumberg E, Fung J, Barin B, Stablein D, Stock PG. Liver transplant outcomes in HIV+ haemophilic men. Haemophilia. 2013 Jan;19(1):134-40. doi: 10.1111/j.1365-2516.2012.02905.x. Epub 2012 Jul 5.
citation: Ansari IU, Allen T, Berical A, Stock PG, Barin B, Striker R. Phenotypic analysis of NS5A variant from liver transplant patient with increased cyclosporine susceptibility. Virology. 2013 Feb 20;436(2):268-73. doi: 10.1016/j.virol.2012.11.018. Epub 2013 Jan 2.
citation: Bahirwani R, Barin B, Olthoff K, Stock P, Murphy B, Rajender Reddy K; Solid Organ Transplantation in HIV: Multi-Site Study Investigators. Chronic kidney disease after liver transplantation in human immunodeficiency virus/hepatitis C virus-coinfected recipients versus human immunodeficiency virus-infected recipients without hepatitis C virus: results from the National Institutes of Health multi-site study. Liver Transpl. 2013 Jun;19(6):619-26. doi: 10.1002/lt.23648.
citation: Chin-Hong P, Beatty G, Stock P. Perspectives on liver and kidney transplantation in the human immunodeficiency virus-infected patient. Infect Dis Clin North Am. 2013 Jun;27(2):459-71. doi: 10.1016/j.idc.2013.02.010. Epub 2013 Mar 29.
citation: Frassetto L, Floren L, Barin B, Browne M, Wolfe A, Roland M, Stock P, Carlson L, Christians U, Benet L. Changes in clearance, volume and bioavailability of immunosuppressants when given with HAART in HIV-1 infected liver and kidney transplant recipients. Biopharm Drug Dispos. 2013 Nov;34(8):442-51. doi: 10.1002/bdd.1860. Epub 2013 Sep 12.
citation: Gregg KS, Barin B, Pitrak D, Ramaprasad C, Pursell K. Acquired hypogammaglobulinemia in HIV-positive subjects after liver transplantation. Transpl Infect Dis. 2013 Dec;15(6):581-7. doi: 10.1111/tid.12139. Epub 2013 Sep 18.
citation: Roland ME, Barin B, Huprikar S, Murphy B, Hanto DW, Blumberg E, Olthoff K, Simon D, Hardy WD, Beatty G, Stock PG; HIVTR Study Team. Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls. AIDS. 2016 Jan 28;30(3):435-44. doi: 10.1097/QAD.0000000000000934.
citation: Stock PG, Terrault NA. Human immunodeficiency virus and liver transplantation: Hepatitis C is the last hurdle. Hepatology. 2015 May;61(5):1747-54. doi: 10.1002/hep.27553. Epub 2015 Mar 19. No abstract available.
citation: Sherman KE, Terrault N, Barin B, Rouster SD, Shata MT; HIV-TR Investigators. Hepatitis E infection in HIV-infected liver and kidney transplant candidates. J Viral Hepat. 2014 Aug;21(8):e74-7. doi: 10.1111/jvh.12233. Epub 2014 Apr 28.
citation: Frassetto LA, Tan-Tam CC, Barin B, Browne M, Wolfe AR, Stock PG, Roland M, Benet LZ. Best single time point correlations with AUC for cyclosporine and tacrolimus in HIV-infected kidney and liver transplant recipients. Transplantation. 2014 Mar 27;97(6):702-7. doi: 10.1097/01.TP.0000441097.30094.31.