A comparison of tenofovir-associated renal function changes in HIV-infected African Americans vs Caucasians.
ABSTRACT The effects of tenofovir on renal function have been measured in multiple studies. Although African Americans are at a higher risk of developing chronic kidney disease, there are limited data examining the influence of race on tenofovir-related nephrotoxicity.
This was a retrospective study of human immunodeficiency virus (HIV)-infected patients at a university-affiliated HIV clinic who were prescribed tenofovir between July 1, 2001, and January 31, 2009. The primary outcome was mean change in creatinine clearance. Secondary endpoints assessed the odds of tenofovir discontinuation secondary to nephrotoxicity, and prevalence of grade 2 to 4 serum creatinine elevation and hypophosphatemia during treatment.
A total of 65 African American and 186 Caucasian patients were included. There were no statistically significant differences in mean change in creatinine clearance, as estimated by the Cockcroft-Gault (-14.2 mL/min vs -15.9 mL/min [P = .525]) and modification of diet in renal disease formulas (-17.2 mL/min/1.73 m2 vs -15.6 mL/min/1.73 m2 [P = .585]) between African Americans and Caucasians. Rates of tenofovir discontinuation secondary to nephrotoxicity were 6.2% and 1.6%, respectively (P = .076). Elevated baseline serum creatinine and female gender may be potential predictors for tenofovir discontinuation.
There were no statistically significant differences in tenofovir-related renal function changes by race as observed in our HIV patient population.
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ABSTRACT: Kidney transplantation in HIV-infected patients is associated with a higher rate of graft rejection as well as an increased toxicity of the immunosuppressive therapy. Specifically, the use of the calcineurin inhibitor tacrolimus is problematic because of a narrow therapeutic range, a high interindividual variability of trough levels, and multiple interactions with combination antiretroviral therapy (cART). Our objective was to establish the optimal individual immunosuppressive dose for the time after kidney transplantation. We administered a temporary course of immunosuppressive therapy in three HIV-infected patients with end-stage renal disease (ESRD) after wait-listing and prior to transplantation for deceased donor kidney transplantation. Starting with a tacrolimus dose of 1 mg twice daily, the dose was titrated to reach a tacrolimus trough level of 8-12 ng/ml. HIV had been diagnosed 7-14 years prior. All patients had no detectable HIV-1 RNA while on cART. All three patients had been on chronic dialysis for 4, 7, and 10 years. In two patients, the intended tacrolimus trough levels of 8-12 ng/ml were achieved within a month. The required tacrolimus dose ranged from 0.5 mg thrice weekly to 10 mg daily. In one case, ventricular tachycardia occurred, so the immunosuppressive therapy was switched to cyclosporine A. So far, two patients have been transplanted successfully. In summary, dose-finding of immunosuppressive therapy with tacrolimus in patients on cART before renal transplantation is feasible and appears useful to minimize immunosuppressive therapy-related complications in the post-transplantation period.Transplant International 12/2012; 26(3). DOI:10.1111/tri.12020 · 3.16 Impact Factor
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ABSTRACT: The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field. Several individual antiretroviral agents (ARVs) including tenofovir and several protease inhibitors have, in diverse study settings, been associated with renal impairment. Traditional renal risk factors are common among those experiencing adverse renal impairment to ARVs, but do not fully explain why only some develop these effects. Discontinuation of nephrotoxic ARVs is common with declining renal function, but has unknown long-term consequences. Immune suppression is a strong independent risk factor for renal impairment, and ongoing investigations will clarify whether initiating ARVs with nephrotoxic properties at higher CD4 cell counts will have net beneficial effects on renal function. With improvements in survival, multiple risk factors have emerged for renal impairment in HIV-positive persons. Although certain ARVs may cause moderate renal impairment, effects on more severe renal impairment remain unresolved. Regular renal function monitoring allow for switching away from nephrotoxic ARVs in case of decreasing function. If such actions prove beneficial higher prevalence of ARV-associated severe renal impairment may emerge in populations without access to regular monitoring.Current opinion in HIV and AIDS 11/2013; DOI:10.1097/COH.0000000000000023 · 4.39 Impact Factor