Tenofovir disoproxil fumarate co-administered with lopinavir/ritonavir is strongly associated with tubular damage and chronic kidney disease

Backgroud: With expanding antiretroviral therapy (ART) in a resource-limited setting, the use of second line ART with ritonavir boosted lopinavir (LPV/r) is increasing. However, little is known regarding the renal safety of tenofovir (TDF) co-administered with LPV/r. Methods: In total 1382 HIV-infected patients were enrolled and data were recorded twice ( October 2014 and 2015) in Vietnam. Tubular dysfunction (TD) was defined as urinary beta 2 microglobulin (beta 2MG) > 1000 mu g/L at both timepoints or increase in beta 2MG by > 2000 mu g/L. Chronic kidney disease (CKD) was defined as creatinine clearance <= 60 ml/min or urinary protein/creatinine ratio >= 0.15 g/gCre at both timepoints. Results: The patients'mean weight and age were 55.9 kg and 38.4 years, respectively, and 41.5% were female. Additionally, 98.2% were on ART, 76.3% were on TDF (mean exposure duration was 35.4 months), and 22.4% had never TDF exposure. TD and CKD were diagnosed in 13% and 8.3% of all patients, respectively. In multivariate analyses, age (OR = 1.057; 95%CI, 1.034-1.081), being female (OR = 0.377; 95%CI, 0.221-0.645), HBsAg positive (OR = 1.812; 95%CI, 1.134-2.894), HCVAb positive (OR = 1.703; 95%CI, 1.100-2.635), TDF exposure (OR = 9.226; 95%CI, 2.847-29.901) and LPV/r exposure (OR = 5.548; 95%CI, 3.313-9.293) were significantly associated with TD. Moreover, age (OR = 1.093; 95%CI, 1.0681.119), being female (OR =0.510; 95%CI, 0.295-0.880), weight (OR = 0.909; 95%CI,0.8790.939), hypertension (OR= 3.027; 95%CI, 1.714-5.347), TDF exposure (OR = 1.963; 95%CI, 1.027-3.7 53) and LPV/r exposure (OR = 3.122; 95%CI, 1.710-5.699) were significantly associated with CKD. Conclusions: TDF and LPV/r exposure were strongly associated with TD and CKD, in addition to their known risks. Therefore, attention to renal safety for patients on second line ART is necessary. (c) 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.