In this nonrandomized prospective trial, 125 liver and 150 kidney HIV-infected transplant recipients were followed for a median of 2.3 [IQR 1.0, 3.7] and 2.7 [IQR 1.9, 4.1] years respectively at 21 U.S. transplantation centers (all cases had at least 1 year of follow up, except 8 liver recipients with 110 to 352 days of follow-up). The research protocol was approved and monitored by the institutional review boards at all participating centers, and each patient provided written informed consent.
Inclusion requirements included; 1. CD4+ T-cell (CD4) counts > 200 cells per cubic millimeter and undetectable plasma HIV-1 RNA levels (<50 copies per milliliter) for kidney transplant recipients; 2) CD4 counts >100 cells per cubic millimeter and undetectable or likely suppressible (in the event of hepatotoxicity to anti-retroviral drugs) HIV RNA plasma levels for liver transplant recipients; and 3) absence or history of treated opportunistic infections with the exception of chronic cryptosporidiosis, multifocal leukoencephalopathy, and visceral Kaposi’s sarcoma.
Kidneys or livers from both deceased and living donors were utilized. Maintenance immunosuppression included corticosteroids, cyclosporine or tacrolimus, and mycophenolate mofetil. In patients with calcineurin inhibitor nephrotoxicity, sirolimus was used. Induction therapy with antibody preparations including interleukin-2-receptor blockers, antithymocyte globulin, or both was permitted at the discretion of the treating physicians for kidney transplant recipients. There were no absolute restrictions in anti-retroviral therapy, and most candidates were maintained on the anti-retroviral therapy that was effective in controlling HIV at the time of referral. Doses of drugs requiring renal clearance were based on the patient’s kidney function. Potential nephrotoxicity of antiretroviral agents as well as antimicrobials used to treat opportunistic infections was considered and these medications were changed as indicated.
Standard post-transplantation prophylaxis for opportunistic infections included lifelong therapy to prevent Pneumocystis jiroveci, fungus (1 month), and cytomegalovirus (CMV) (3 months) infections. Prophylaxis against Mycobactrium avium coplex with macrolide antibiotics was required when the CD4+ T-cell count dropped below 75 cells per cubic millimeter. Liver transplant recipients coinfected with Hepatitis B virus received Hepatitis B immune globulin and antiviral (HBV) therapy following transplantation. Hepatitis C virus infected liver recipients were treated for recurrent disease with interferon and ribavirin when they developed cholestatic hepatitis or evidence of fibrosis on liver biopsy.
Patients were evaluated before transplantation and 13 times during the first year after transplantation. During years 2 and 3 post transplantation patients were evaluated every 3 months, then every 6 months in years 4 and 5. Data collected included demographic characteristics, medical history, immunosuppressant and antiretroviral medications, immunosuppressant levels, HIV-1 RNA levels, CD4+ T-cell counts, Hepatitis C virus infection, MELD score, body mass index (BMI), and donor history. Measured outcomes included patient and graft survival, and surgical complications following transplantation. All analysis was conducted with follow up data as of November 14th, 2010.
For surgical complications with a sample size of 7 or more, proportional hazards models were fit to determine whether each complication as a time-varying covariate was associated with death or graft loss. All surgical complications from the univariate graft loss analysis with P<0.10 were evaluated in a multivariate model adjusted for other potential risk factors for graft loss including pre-transplant CD4 count, viral load at enrollment, Hepatitis C virus infection, dual Liver/Kidney transplant, pre-transplant BMI, donor age, initial calcineurin inhibitor (CNI) use (Tacrolimus vs. Cyclosporin A).
Univariate proportional hazards models were fit to examine the impact of baseline predictors on each surgical complication with sample size of 7 or more. The baseline factors evaluated included: age, sex, race, CD4 pre-transplant nadir/level at study enrollment/most recent pre-transplant (per 50 cells/μL), viral load at enrollment and pre-transplant, HCV infection status, dual liver/kidney transplant, MELD score pre-transplant, BMI at enrollment or pre-transplant, initial thymoglobulin therapy, opportunistic infection history, donor source/age/HCV infection status/marginal status, extended criteria donor (ECD). A search of the PubMed database for keywords HIV infection, kidney transplantation, liver transplantation, and surgical complications yielded relevant journal articles citing rates of surgical complications in non-HIV infected transplant recipients.