This study will examine the safety and effectiveness of renal (kidney) transplantation for
HIV-infected patients with end-stage renal disease (kidney failure). Although kidney
transplant is the best treatment for most causes of kidney failure, people infected with HIV
are not offered this procedure because the immunosuppressive drugs (drugs that suppress
immune function) required to prevent organ rejection could further impair the patient's
already weakened immune system. This study will use a regimen of immunosuppressants
designed to complement treatment for patients taking highly active antiretroviral therapy
HIV-infected patients between 18 and 60 years of age with renal failure who have not had any
opportunistic infections for 5 years may be eligible for this study. Candidates will be
screened with a medical history, physical examination, and blood and urine tests.
Before the transplant procedure, participants will undergo additional tests and procedures,
including blood studies, 24-hour urine collection, infectious disease consultation,
tuberculin skin test, PAP smear for women, chest X-ray, brain and hip MRI studies and
DEXA-scan to evaluate bone density. In addition, patients may undergo leukapheresis to
obtain white blood cells for study. For this procedure, whole blood is drawn through a
needle in an arm vein and passed through a cell separator machine. The white cells are
collected for removal, and the rest of the blood is returned to the body through the same
needle or another needle in the other arm.
When a donor organ becomes available for transplant, the patient will receive three
anti-rejection drugs-cyclosporine, mycophenolate mofetil and prednisone-to prevent organ
rejection. Immediately after the surgery, HAART drugs will be stopped for 7 days until
stable levels of the immune suppressants can be achieved. Then, HAART will be re-started
and all medications will be adjusted to achieve adequate blood levels. Patients must stay
in the local area 60 days after discharge from the hospital for monitoring. Frequent blood
samples will be taken to monitor kidney function, viral load and CD4+ T cell counts.
Follow-up visits will then be scheduled monthly for the first 6 months after transplant,
then every other month for 1 year. Kidney biopsies will be done at the end of the first
month, after 6 months, and yearly for 5 years. For the biopsy, a special needle is used to
remove a small piece of kidney tissue for microscopic examination. The biopsies and blood
tests are done to evaluate the immune response to the transplanted organ and to study how
HAART interacts with the immune suppressing drugs.
Renal allotransplantation is the treatment of choice for most causes of end-stage renal
disease (ESRD). However, successful transplantation is dependent on the use of potent
immunosuppressive drugs to prevent immune mediated rejection of the transplanted organ.
Patients who have become infected with the Human Immunodeficiency Virus (HIV) have an
underlying immune deficit resulting primarily from the virus's affect on CD4+ T lymphocytes.
Many of these individuals also develop ESRD. However, patients with HIV infection have
been excluded from allotransplantation. This has been based on the premise that the immune
suppression required for transplantation would adversely affect their already compromised
immune system. Recently, the treatment of HIV infection has improved dramatically,
particularly with the advent of protease inhibitors (PI) and their inclusion in highly
active anti-retroviral therapy (HAART) protocols. Additionally, some immunosuppressant
drugs have actually been shown to limit the replication and spread of HIV in vitro. Thus,
the treatment of HIV associated ESRD with allotransplantation may be feasible.
This protocol is a pilot trial investigating the potential utility of renal transplantation
to treat ESRD in patients infected with HIV. Ten patients with controlled HIV infection
will receive renal allografts under an immunosuppressive regimen designed to complement
HAART protocols. Immune system monitoring will be performed specifically to evaluate the
effect of immunosuppressive drugs on the T cell function and viral burden of allograft
recipients. The allograft will be periodically evaluated to assess the prevalence of
disease recurrence or rejection. Pharmacokinetic evaluation will be performed to define the
interactions between HAART and immunosuppressive drug regimens. Long-term outcome will be
assessed at 1 and 5 years and compared to contemporaneous outcomes for non-infected patients
receiving the standard of care. It is hoped that this protocol will suggest ways of
providing HIV infected patients with renal replacement therapy without jeopardizing their
control over their viral infection.
Patients must have documented HIV infection (by any licensed ELISA and confirmation by
Western Blot), with confirmation of infection by the clinical pathology lab at the Warren
G. Magnuson Clinical Center will be eligible.
Patients with renal failure as defined by a creatinine clearance on 24 hour urine
collection of less than 20.
Patients must be of the ages of 18-60.
Patients must have the willingness and legal ability to give informed consent, or
permission from a legal guardian.
Patients must have the willingness to travel to the Clinical Center for protocol specific
samples to be taken, or in some cases, the ability to send samples via overnight mail.
Patients must have a current CD4+ T-cell count of greater than or equal to 300/mm(3) for 9
months or longer.
Patients must have a CD4 nadir over course of infection not less than 200/mm(3).
Patients must have current HIV-1 RNA of less than or equal to 50 RNA copies/ml for 9
months or longer. (Intermittent elevations of less than or equal to 500 copies/ml, if not
persistent on more than two sequential measures and followed by undetectable levels, are
Patients must be on a stable HAART -regimen for greater than or equal to 3 months prior to
entry. The HAART regimen must consist of at least 3 drugs and include at least 2 classes
of drugs. Individuals with sustained viral suppression on a regimen of abacavir plus 2
other nucleoside reverse transcriptase inhibitors will be eligible at the discretion of
the investigators. The use of hydroxyurea will not be permitted.
Patients must have a willingness to comply with all study medications.
Patients must have a willingness to disclose HIV status to their living donor prior to
transplant if a living donor is the source of their kidney.
Patients must provide adequate medical history documentation to allow for the accurate
determination of the severity of one's prior HIV disease status.
Patients must not have a history of any AIDS defining opportunistic infections within 5
years of enrollment.
Patients must not have a history of any malignant neoplasm except in situ anogenital
carcinoma, adequately treated basal or squamous cell carcinoma of the skin, or solid
tumors treated with curative therapy and disease free for at least 5 years.
Patients must not have infection with a quasi-species of HIV that, based on review of
clinical data, antiretroviral treatment history, and available viral genotypes/phenotypes,
leaves limited options for successful suppression of viral replication should the
patient's current regimen fail.
Patients must have the ability and willingness to comply with immunosuppression protocol,
antiretroviral therapy, and/or HIV monitoring and therapy if indicated.
Patients must not have concomitant conditions that, in the judgement of the investigators,
would preclude transplantation or immunosuppression.
Patients must not have a condition that precludes serial follow-up.
Patients must not have significant coagulopathy or requirement for anticoagulation therapy
that would contraindicate protocol allograft biopsies.
Donors who are EBV positive when the recipient is EBV negative will be excluded.
Donors who are CMV positive when the recipient is CMV negative will be excluded.
Patients must not have a history of or active infection with hepatitis B or hepatitis C
virus for the first 5 patients. After 5 patients without concomitant hepatitis have been
enrolled and followed for 6 months, patients with hepatitis infection without significant
fibrosis on liver biopsy will be considered for enrollment.
Subjects with a positive donor T cell crossmatch (current or historical) will be excluded.
No peak panel reactive antibody greater than 20 percent that is the result of anti-HLA
In addition the above-mentioned criteria, the donor must be HIV, HCV, and HBV negative.
EBV and CMV mismatched donors (positive to negative combinations) will also be excluded.