Kidney and Liver Transplantation in People With HIV

HIV Infections Clinical Trial

Official title:

Solid Organ Transplantation in HIV: Multi-Site Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00074386
• Other study ID #: 1U01AI052748
• Secondary ID: 1U01AI052748
• Status: Completed
• Phase: N/A
• First received: December 11, 2003
• Last updated: January 16, 2014
• Start date: October 2003
• Est. completion date: August 2013

Study information

• Verified date: January 2014
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00023478
• NCT00473629

Recruitment information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections
• Kidney Disease
• Kidney Diseases
• Liver Disease
• Liver Diseases

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	The University Hospital, Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cedar-Sinai Hospital	Los Angeles	California
United States	University of Miami, Jackson Memorial Medical Center	Miami	Florida
United States	Tulane University	New Orleans	Louisiana
United States	Columbia Presbyterian Hospital	New York	New York
United States	Mt. Sinai Medical Center	New York	New York
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh, Thomas E. Starzl Institute	Pittsburgh	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	Georgetown University	Washington	District of Columbia
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (24)

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 — View 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 recip — View 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 matr — View 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. — View 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. Review. — View 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;1 — View 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 — View 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. — View 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. Epub 2007 O — View 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. Review. — View 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. A — View 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. — View 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. Surge — View 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. Review. — View 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 20 — View 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. Review. — View Citation

Roland ME, Stock PG. Liver transplantation in HIV-infected recipients. Semin Liver Dis. 2006 Aug;26(3):273-84. Review. — View 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. Review. — View 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 transplantati — View Citation

Stock PG, Roland ME. Evolving clinical strategies for transplantation in the HIV-positive recipient. Transplantation. 2007 Sep 15;84(5):563-71. — View 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 HI — View 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. Review. — View 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. — View 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. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subject survival		5 years	Yes
Primary	graft survival		5 years	Yes
Secondary	Opportunistic complications		5 years	Yes
Secondary	CD4+ T cell counts and HIV-1 RNA levels		5 years	Yes
Secondary	viral markers and host-response (CFC and ELISPOT) to viral co-pathogens, including HBV, HCV,CMV, EBV, HHV-6, HHV-8, and HPV		5 years	Yes
Secondary	rejection rates and markers of alloresponse		5 years	Yes
Secondary	pharmacokinetic interactions between immunosuppressive agents and antiretrovirals		5 years	Yes

External Links

•   Click here for participating centers, contact information, and additional information on this study