Higher Rates of Rejection in HIV-infected Kidney Transplant Recipients on Ritonavir-Boosted Protease Inhibitors-Three-Year Follow Up

Abstract

Background One-year rejection rates in HIV-infected kidney transplant recipients range from 15-40%, compared to overall rejection rates of 10% in HIV-negative patients. Protocols for immunosuppression and highly active antiretroviral therapy (HAART) vary substantially and there is potential for significant drug-drug interactions, specifically between ritonavir-boosted protease inhibitors (rtv+ PI) and calcineurin inhibitors. Methods This is an IRB-approved, single center, retrospective study of adult HIV-infected patients who underwent a kidney transplantation between 5/2009 to 12/2014 with a three-year follow up for each patient. Results Forty-two patients were identified with a median age of 52 (47, 57) years. Of these, 81% were male and 50% were African American, 29% were Hispanic, and 17% were Caucasian. The most common cause of renal failure was hypertensive nephrosclerosis (50%) followed by HIV-associated nephropathy (14%), and the median duration of pre-transplant dialysis was 5.8 (2.8, 8.7) years. All patients were induced with IL-2 receptor antagonist (IL-2 RA): 83% with basiliximab and 17% with daclizumab induction. Calcineurin inhibitor therapy included tacrolimus (76%), cyclosporine (17%), or transitions between these two (7%). 40% of patients received a rtv+ PI-based HAART regimen. At 30 days, patient and graft survival were 100%. Patient and graft survival were consistent at 93% and 90%, respectively, at years one, two, and three. Overall treated biopsy-proven rejection rates at one, two, and three years were 38%, 38%, and 41%, respectively, and 92% of these episodes were acute rejection. At one, two, and three years, rejection rates were significantly higher for recipients on rtv+PI compared to those on other HAART regimens as 59% vs 24% (p=0.029), 59% vs 24% (p=0.029), and 68% vs 24% (p=0.01), respectively. Conclusion HIV-infected kidney transplant recipients maintain excellent outcomes despite higher rates of acute rejection relative to HIV negative recipients. Given the significantly higher rates of rejection at one, two, and three years in the rtv + PI group, alternative HAART regimens should be considered prior to transplant when possible.