CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

A. Albertazzi¹, S. Cocchi², S. De amicis¹, G. Ghiandai¹, F. Damiano¹, V. Albertazzi¹, E. Rubbiani¹, M. Giovannoni¹, B. Baisi³, G. Guaraldi², G. Cappelli^1
1Nephrology Dialysis And Renal Trasplantation Unit, University Hospital of Modena, Modena/ITALY, ²Clinic Of Infectious Diseses, University Hospital of Modena, Modena/ITALY, ³Department Of Urology, University Hospital of Modena, Modena/ITALY

Body: Introduction. Highly active antiretroviral therapy (HAART) improves HIV-related mortality and morbidity rates, resulting in a better long-term survival and in a reassessment of kidney transplantation (KTx) for HIV-infected patients with end-stage renal disease. However, it involves some risks connected to acute rejection (AR), interactions between antiretrovirals (ARVs), particularly protease inhibitors, and immunosuppressive drugs (IS), viral and opportunistic infections. Since safety should come first in a not-life-saving transplant, we designed a soft immunosuppression schedule. We aimed to evaluate outcomes and pharmacokinetic interactions (PKI) between a "bridge" antiretroviral therapy (BART) based on enfuvirtide (T20) and/or raltegravir (RAL) in the immediate post-operative (po) period and IS - everolimus (Ev) and low-dose Cyclosporine (CyA) - among HIV-infected individuals undergoing KTx. Methods. After basiliximab and steroid induction, CyA was introduced at 2-2.5 mg/kg bid when serum creatinine was <2.5 mg% with peak at 2h (C2) targeted around 1000 ng/mL, then it was halved and combined with Ev 0.75 mg bid from 21^st po day (pod) (target through level concentration (TLC): 8-10 ng/mL and C2: 400-500 ng/mL) with a rapid steroid tapering to 4 mg/day within 45 days. Maintenance was made by Ev (TLC: 6-8 ng/mL) and CyA (C2: 250-350 ng/mL). The protocol was amended after the fifth transplant and mycophenolic acid (MPA) was then added till pod 30. BART consisting of T20 in combination with 2 nucleos(t)ide analogues or 1 nucleos(t)ide analogue and RAL was introduced on the immediate po period (1^st-2^nd pod). Results. From March 2008 to December 2009, 6 patients (4 males, 2 females; median age 47.5 years; range 38-59) underwent KTx. Patient and graft survivals were 100% and 83%, respectively. Case 5 experienced an early rhabdomyolysis which postponed introduction of CyA and led to a steroid-resistant biopsy-proven AR and to transplantectomy on 31 pod. No CMV reactivations neither opportunistic infections were documented. Once achieved IS steady state BART was modified: T20 was replaced with atazanavir (ATV) in cases 1, 3 and 4, with fosamprenavir (fAPV) in patient 6, while in case 2 RAL was used because a pre-transplant intolerance to ATV. In patient 3 it was necessary to switch ATV to fAPV for bradycardia. ART regimens were effective from the immuno-virological point of view in all patients except case 2 who, for transient detectable HIV viremia, had ART effectively enhanced. After a median follow up of 11.5 months (range 2-22), ART consisted of lamivudine (3TC)+RAL+ATV in cases 1 and 4, 3TC+RAL+fAPV in patients 3 and 6, 3TC+abacavir (ABC)+RAL+darunavir+ritonavir (RTV) in case 2 and 3TC+tenofovir+ABC+ATV+RTV in patient 6. At present, steroid is off in 3 out of 5 patients and IS concentrations are stable with a median value of MDRD of 55.5 ml/min (range 19.5-76). Conclusions. This is the first report of ARVs and Ev association. In our series Ev was safe and effective with optimal patient survival rates. Short-term MPA offers a stronger protection against the risk of AR during delayed graft function. RAL and T20 did not alter appreciably Ev and CyA concentrations, confirming the low potential for PKI with IS.

Disclosure: All authors have declared no conflicts of interest.