ritonavir and AIDS-Associated-Nephropathy

Ritonavir is an extremely strong inhibitor of P450 cytochrome 3A, which is the main metabolizing enzyme of tacrolimus. Subsequently, the pharmacokinetics of tacrolimus are affected to a large extend by the coadministration of ritonavir in HIV-infected transplant recipients. Therefore, to prevent overexposure directly posttransplantation in HIV-infected patients on ritonavir-containing cART, the predictive value of a pretransplantation pharmacokinetic curve of tacrolimus was explored.. A pretransplantation pharmacokinetic model of tacrolimus in these patients was developed, and a posttransplantation dosing advice was established for each individual patient. The pharmacokinetic population parameters were compared with HIV-negative patients, and predictive value of the pretransplantation curves was assessed in patients after the transplantation procedure.. No significant difference was found between the model-predicted and actual posttransplantation 24 h-tacrolimus levels (14.6 vs. 17.8 ng/mL, P=0.19). As the simulated pharmacokinetic curves lacked an absorption peak every 12 h, the mean 12 h-AUC was approximately 40 % lower compared with AUC's reported in HIV-negative recipients, when similar trough levels were targeted.. In conclusion, pretransplantation curves of tacrolimus seem a promising tool to prevent overexposure directly posttransplantation in patients on ritonavir-containing cART and raising trough levels to achieve an exposure equivalent to HIV-negative recipients is suggested.

Topics: Adult; AIDS-Associated Nephropathy; Area Under Curve; Biotransformation; Computer Simulation; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Drug Monitoring; Enzyme Inhibitors; HIV Infections; HIV Protease Inhibitors; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Models, Biological; Pilot Projects; Ritonavir; Tacrolimus

An HIV-infected asymptomatic woman developed acute kidney injury six weeks after initiation of combination antiretroviral therapy (cART). A renal biopsy revealed both renal-limited sarcoidosis and HIV nephropathy. The acute renal injury reversed with glucocorticoid therapy.

Topics: Acute Kidney Injury; Adenine; Adult; AIDS-Associated Nephropathy; Anti-Retroviral Agents; Atazanavir Sulfate; Female; HIV Infections; Humans; Oligopeptides; Organophosphonates; Prednisone; Pyridines; Ritonavir; Sarcoidosis; Tenofovir; Young Adult

To examine long-term effects of antiretroviral therapy (ART) on kidney function, we evaluated the incidence and risk factors for chronic kidney disease (CKD) among ART-naive, HIV-infected adults and compared changes in estimated glomerular filtration rates (eGFR) before and after starting ART.. Multicenter observational cohort study of patients with at least one serum creatinine measurement before and after initiating ART. Cox proportional hazard models, and marginal structure models examined CKD risk factors; mixed-effects linear models examined eGFR slopes.. Three thousand, three hundred and twenty-nine patients met entry criteria, contributing 10 099 person-years of observation on ART. ART was associated with a significantly slower rate of eGFR decline (from -2.18 to -1.37 ml/min per 1.73 m per year; P = 0.02). The incidence of CKD defined by eGFR thresholds of 60, 45 and 30 ml/min per 1.73 m was 10.5, 3.4 and 1.6 per 1000 person-years, respectively. In adjusted analyses black race, hepatitis C coinfection, lower time-varying CD4 cell count and higher time-varying viral load on ART were associated with higher CKD risk, and the magnitude of these risks increased with more severe CKD. Tenofovir and a ritonavir-boosted protease inhibitor (rPI) was also associated with higher CKD risk [hazard odds ratio for an eGFR threshold <60 ml/min per 1.73 m: 3.35 (95% confidence interval (CI) = 1.40-8.02)], which developed in 5.7% of patients after 4 years of exposure to this regimen-type.. ART was associated with reduced CKD risk in association with CD4 cell restoration and plasma viral load suppression, despite an increased CKD risk that was associated with initial regimens that included tenofovir and rPI.

Topics: Adenine; Adult; AIDS-Associated Nephropathy; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Creatinine; Female; Glomerular Filtration Rate; Hepatitis C; HIV Seropositivity; HIV-1; Humans; Incidence; Male; Middle Aged; Organophosphonates; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Ritonavir; Tenofovir; United States; Viral Load

Topics: AIDS-Associated Nephropathy; HIV Protease Inhibitors; HIV-1; Humans; Male; Middle Aged; Renal Dialysis; Ritonavir; Saquinavir