Plasma tenofovir trough concentrations are associated with renal dysfunction in Japanese patients with HIV infection: a retrospective cohort study.
BACKGROUND
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.


METHODS
A 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.


RESULTS
The 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).


CONCLUSIONS
Despite 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.
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Yusuke
Y
Kunimoto
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Hiroshi
H
Ikeda
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Satoshi
S
Fujii
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Manabu
M
Kitagawa
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Kieko
K
Yamazaki
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Hiromasa
H
Nakata
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Norimasa
N
Noda
Department of Hematology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo, 150-8935 Japan.
Tadao
T
Ishida
Department of Hospital Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543 Japan.
Atsushi
A
Miyamoto
Combination antiretroviral therapy; HIV; Plasma tenofovir trough concentration; Renal dysfunction; Tenofovir disoproxil fumarate; Therapeutic drug monitoring
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