Coadministration with lopinavir/ritonavir is contraindicated. Darunavir/cobicistat should not be used in combination with another antiretroviral that requires pharmacoenhancement since dosing recommendations for such combination have not been established. Darunavir/cobicistat should not be used concurrently with products containing ritonavir or regimens containing ritonavir.

Darunavir/cobicistat is not recommended in combination with other antiretroviral drugs that require pharmacokinetic boosting (i.e., another protease inhibitor) because dosing recommendations for such combinations have not been established and co-administration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance.

According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended.