Higher Tenofovir Trough Concentrations and Renal Dysfunction
High trough levels of tenofovir, seen in half the patients taking the drug, were associated with renal impairment.
Tenofovir is a common component of current antiretroviral therapy (ART) regimens. It is excreted by the kidney and has been associated with a low risk for clinically significant renal dysfunction during the first years of use. In France, due to concern about the renal effects of tenofovir, concentrations of this drug are often monitored during the first 12 months of use. Now, investigators have retrospectively assessed the association between tenofovir trough concentrations and glomerular filtration rate (GFR) in HIV-infected patients on tenofovir-containing regimens who were seen at one clinic in France between December 2006 and January 2010.
The study involved 163 patients (median age, 47; 30% women; median CD4 count, 382 cells/mm3; 68% with viral load <40 copies/mL) for whom at least one determination of tenofovir trough concentration (measured 17 to 24 hours after dosing) was available for analysis. Median durations of ART and tenofovir use at the time of testing were 8.7 and 21.1 months, respectively. GFR was assessed at the start of tenofovir-based ART, at tenofovir trough determination, and at 12 months in patients still on the same ART regimen.
Overall, tenofovir trough concentrations were below the level of detection (<40 ng/mL) in 12% of participants, within the expected range (40–90 ng/mL) in 37%, and high (>90 ng/mL) in 52%; the median trough concentration in the high-level group was 130 ng/mL. A significant decrease in GFR between baseline and trough determination (–8.5 mL/min) was seen only in the high-level trough group and was most pronounced in women. Multivariate analysis stratified by sex showed that older age and a higher baseline GFR level were associated with decreased GFR in both sexes, and that high-level tenofovir trough concentration was associated with decreased GFR in women; diabetes, hypertension, hepatitis C virus coinfection, and protease inhibitor use showed no association. At 12 months, high-level tenofovir trough concentration was significantly associated with decreased GFR in both men and women.
CITATION(S):
Poizot-Martin I et al. Renal impairment in patients receiving a tenofovir-cART regimen: Impact of tenofovir trough concentration. J Acquir Immune Defic Syndr 2013 Apr; 62:375.
