Pharmacokinetic interaction: atazanavir exposure in presence of tenofovir disoproxil fumarate plus ritonavir

This entry describes a specific drug-drug interaction (DDI) between atazanavir, tenofovir disoproxil fumarate (TDF), and ritonavir used in HIV-1 therapy. Atazanavir is an HIV-1 protease inhibitor that serves as a substrate for the CYP3A4 enzyme. When co-administered with TDF, atazanavir plasma concentrations (AUC and Cmin) are significantly decreased, potentially compromising antiviral efficacy (Source: FDA Reyataz Prescribing Information). To mitigate this, ritonavir is co-administered as a pharmacokinetic booster to inhibit CYP3A4 and restore atazanavir exposure. This interaction is clinically significant because the combination of atazanavir/ritonavir and TDF has been linked to increased tenofovir concentrations, raising the risk of renal impairment and Fanconi syndrome. Monitoring of renal function and viral load is essential for patients on this regimen to balance efficacy and toxicity. The interaction highlights the complexity of managing antiretroviral therapy where metabolic pathways and transport mechanisms overlap.

Other names

Atazanavir-Tenofovir-Ritonavir interactionATV/r + TDF interactionAtazanavir pharmacokinetic boostingAtazanavir-Tenofovir drug-drug interaction

Ritonavir inhibits the Cytochrome P450 3A4 (CYP3A4) enzyme to increase atazanavir exposure, counteracting the reductive effect of tenofovir disoproxil fumarate on atazanavir plasma levels.