Cumulative exposure of TDF is associated with kidney tubulopathy whether it is currently used or discontinued.

OBJECTIVE

Tenofovir disoproxil fumarate (TDF) increases the risk of kidney tubular dysfunction (KTD). This study was conducted to elucidate whether KTD persists after discontinuation of TDF.

DESIGN

A prospective cross-sectional study which enrolled 941 HIV-1-infected patients.

METHODS

KTD was predefined as the presence of at least two abnormalities among the five tubular markers (fractional excretion of phosphate, fractional excretion of uric acid, β2 microglobulinuria, N-acetyl-β-D-glucosaminidase, nondiabetic glycosuria). Logistic regression model was used to examine the association between KTD and cumulative TDF use, as well as current status of TDF use.

RESULTS

In total, 94% of study patients were men (median age 45, estimated glomerular filtration rate 75 ml/min per 1.73 m, CD4 575 cells/μl. About 98% were on antiretroviral therapy. In total, 64% of the patients ever used TDF and 39% currently used TDF. Twenty-nine percent used TDF for more than 5 years. KTD was diagnosed in 116 (12%) patients. In multivariate model, more than 5 years of TDF exposure and current TDF use [odds ratio (OR) 4.2, 95% confidence interval (CI) 2.37-7.56], more than 5 years and past TDF use (OR 2.4, 95% CI 1.09-5.33), less than 5 years and current TDF (OR 2.4, 95% CI 1.24-4.85), and less than 5 years and past TDF (OR 2.4, 95% CI 1.22-4.64) were all significantly associated with KTD, with never TDF use as reference. The results were the same using 4 and 3 years of exposure as the cutoff. However, with 2 years exposure, both less than 2 years and current TDF (OR 2.3, 95% CI 0.84-6.20) and less than 2 years and past TDF (OR 1.9, 95% CI 0.73-4.93) were not associated with KTD, whereas both more than 2 years and current TDF and more than 2 years and past TDF were associated.

CONCLUSION

The association between cumulative TDF use and KTD was strong and robust. The results of the study suggested that TDF-related KTD might persist after discontinuation of TDF if patients used TDF for more than 2 years.