The effect of lopinavir/r on the renal clearance of tenofovir

The findings of this study add weight to an underlying concern of an association between tenofovir-induced nephrotoxicity and concomitant boosted protease inhibitor treatment.

After adjusting for renal function, tenofovir renal clearance was 17.5% slower in HIV+ patients taking lopinavir/ritonavir versus those not taking a protease inhibitor; this is consistent with a renal interaction between the drugs. Additional studies are required to determine the exact mechanism of the interaction with the most obvious focus being on renal transporters.

Here the authors have shown that tenofovir renal clearance was 15% lower in ABCC4 3463G variants compared with wild type and this decreased renal clearance translates into a 32% increased AUC in the subjects with the variant ABCC4. However the authors clearly point out that this was a small cohort of patients and the evaluation of the relationship between genotype and phenotype was retrospective.

A prospective study will be necessary to fully evaluate the contribution of genetics to tenofovir disposition. Also, since the basis of nephrotoxicity is likely to be multifactorial the drug interaction described may just be one factor and prospective studies are clearly needed to identify patients at risk.

Kiser JJ, Carten ML, Aquilante CL, et al. The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther, 2007, (e-pub ahead of print).