Abstract

BackgroundPlasma tenofovir (TFV) trough concentrations may be relevant for tenofovir disoproxil fumarate (TDF)-induced renal dysfunction. The purpose of this study was to determine the association between plasma TFV trough concentrations and TDF-induced renal dysfunction in Japanese patients with human immunodeficiency virus (HIV) infection.MethodsA 48-week, retrospective cohort study was performed with Japanese patients with HIV infection who started a TDF-containing combination antiretroviral therapy regimen. Plasma TFV trough concentrations were obtained at steady state. The following variables were included in the analysis: sex, age, body weight, body mass index (BMI), serum creatinine, CD4+ cell count, HIV-RNA, concomitant medications, comorbidities, plasma TFV trough concentrations, and estimated glomerular filtration rate (eGFR). For comparisons of variables, we used Mann-Whitney U tests or Fisher’s exact tests. Then, variables associated with renal dysfunction in the univariate analysis were entered into correlation analysis.ResultsThe analysis included 11 patients. The rate of decrease in eGFR was significantly correlated with body weight (Spearman correlation = −0.645, p = 0.041), BMI (Spearman correlation = −0.682, p = 0.031), and plasma TFV trough concentrations (Spearman correlation = 0.709, p = 0.025).ConclusionsDespite the small sample size, our findings suggest that higher plasma TFV trough concentrations may cause TDF-induced renal dysfunction. To prevent TDF-induced renal dysfunction, we propose that individual monitoring of plasma TFV trough concentrations should be performed in Japanese patients with HIV infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s40780-016-0056-5) contains supplementary material, which is available to authorized users.

Highlights

  • Plasma tenofovir (TFV) trough concentrations may be relevant for tenofovir disoproxil fumarate (TDF)-induced renal dysfunction

  • Hepatitis C, n (%) Plasma TFV concentration a BMI body mass index, BSA body surface area, eGFR estimated glomerular filtration rate, CKD chronic kidney disease, NNRTIs non-nucleoside reversetranscriptase inhibitors, INSTIs integrase strand transfer inhibitors, TFV tenofovir aValues are reported as median defined as the maximum rate of decrease in eGFR from baseline during the study period

  • When measurement of plasma TFV trough concentrations for individual monitoring purposes in Japanese patients is not possible, we suggest that low body weight or low BMI could serve as a reasonable alternative predictor of TDF-induced renal dysfunction

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Summary

Introduction

Plasma tenofovir (TFV) trough concentrations may be relevant for tenofovir disoproxil fumarate (TDF)-induced renal dysfunction. The purpose of this study was to determine the association between plasma TFV trough concentrations and TDF-induced renal dysfunction in Japanese patients with human immunodeficiency virus (HIV) infection. TDF is rapidly converted to tenofovir (TFV) following absorption, and plasma TFV trough concentrations may be relevant for TDF-induced renal dysfunction. Several studies conducted in Japan reported that low body weight and genetic polymorphisms of drug transporter genes are significantly associated with TDF-induced renal dysfunction [4, 6]. Reports of the association between plasma TFV trough concentrations and TDF-induced renal dysfunction in Japanese patients with human immunodeficiency virus (HIV) infection are lacking. For safe use of TDF in Japan, the risk factors for TDFinduced renal dysfunction in Japanese patients need to be understood

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