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

Tenofovir disoproxil fumarate co-administered with lopinavir/ritonavir is strongly associated with tubular damage and chronic kidney disease.
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Mizushima D, Nguyen DTH, Nguyen DT, Matsumoto S, Tanuma J, Gatanaga H, Trung NV, van Kinh N, Oka S,


Mizushima D, Nguyen DTH, Nguyen DT, Matsumoto S, Tanuma J, Gatanaga H, Trung NV, van Kinh N, Oka S, (click to view)

Mizushima D, Nguyen DTH, Nguyen DT, Matsumoto S, Tanuma J, Gatanaga H, Trung NV, van Kinh N, Oka S,

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Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2018 03 27() pii 10.1016/j.jiac.2018.03.002

Abstract
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 (β2MG) > 1000 μg/L at both timepoints or increase in β2MG by > 2000 μg/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, 1.068-1.119), being female (OR = 0.510; 95%CI, 0.295-0.880), weight (OR = 0.909; 95%CI, 0.879-0.939), 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.

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