Association between tenofovir plasma trough concentrations in the early stage of administration and discontinuation of up to five years tenofovir disoproxil fumarate due to renal function-related adverse events in Japanese HIV-1 infected patients

Hiroki Yagura; Dai Watanabe; Takao Nakauchi; Hiroyuki Kushida; Kazuyuki Hirota; Yasuharu Nishida; Munehiro Yoshino; Tomoko Uehira; Takuma Shirasaka

doi:10.1186/s40780-024-00343-z

Association between tenofovir plasma trough concentrations in the early stage of administration and discontinuation of up to five years tenofovir disoproxil fumarate due to renal function-related adverse events in Japanese HIV-1 infected patients

J Pharm Health Care Sci. 2024 May 10;10(1):20. doi: 10.1186/s40780-024-00343-z.

Authors

Hiroki Yagura¹, Dai Watanabe², Takao Nakauchi³, Hiroyuki Kushida⁴, Kazuyuki Hirota⁵, Yasuharu Nishida⁵, Munehiro Yoshino⁴, Tomoko Uehira⁵, Takuma Shirasaka⁵

Affiliations

¹ Department of Advanced Medicine for HIV Infection, Institute for Clinical Research, NHO Osaka National Hospital, 2-1-14, Hoenzakaa, Chou-Ku, Osaka, 540-0006, Japan. yagura.hiroki.mu@mail.hosp.go.jp.
² Department of Advanced Medicine for HIV Infection, Institute for Clinical Research, NHO Osaka National Hospital, 2-1-14, Hoenzakaa, Chou-Ku, Osaka, 540-0006, Japan.
³ Department of Pharmacy, NHO Kyoto Medical Center, Kyoto, Japan.
⁴ Department of Pharmacy, NHO Osaka National Hospital, Osaka, Japan.
⁵ AIDS Medical Center, NHO Osaka National Hospital, Osaka, Japan.

Abstract

Background: The relationship between plasma tenofovir (TFV) concentration at the beginning of tenofovir disoproxil fumarate (TDF) administration and the development of renal dysfunction during long-term administration of TDF has not been demonstrated yet. The objective of the present study was to determine whether plasma TFV trough concentrations during early TDF administration could serve as an indicator of renal dysfunction when TDF is administered for long periods.

Methods: We included 149 HIV-1 infected Japanese patients who were prescribed TDF. We investigated the relationship between plasma TFV trough concentrations and the rate of discontinuation due to the development of renal dysfunction for up to five years after the start of TDF administration. We also examined how the decrease in renal function over time due to TDF administration was related to factors associated with high TFV levels and plasma TFV trough concentrations.

Results: The median TFV trough concentration in the TDF discontinuation group was 88 ng/mL, which was significantly higher (p = 0.0041), than that in the continuation group (72 ng/mL). Further, using an ROC curve, the cut-off value for TFV trough concentration at which TDF discontinuation was significantly high was found to be 98 ng/mL. Logistic multivariate analysis of factors associated with discontinuation of TDF due to renal function-related adverse events showed that being ≥ 50 years old (OR = 2.96; 95% CI, 1.01-8.64), having eGFR < 80 mL/min/1.73m² at the start of TDF administration (OR = 5.51; 95% CI, 1.83-17.5), and TFV trough concentration ≥ 98 ng/mL (OR = 2.96; 95% CI, 1.16-7.60) were independent factors.

Conclusions: The results suggested that the importance of measuring TFV concentrations to evaluate the risk of developing renal function-related adverse events during long-term TDF administration.

Keywords: Plasma trough concentration; Renal dysfunction; Tenofovir.

Grants and funding

JP23fk0410050/the Japan Agency for Medical Research and Development