Therapeutic drug monitoring (TDM) constitutes a compelling approach for the optimization of antiretroviral therapy in treatment-experienced HIV-1 patients. While various inhibitory indices have been proposed to predict virologic outcome, there is a lack of consensus on the clinical value of TDM. Here, we report the comparative results of TDM in 14 HIV-1-infected patients who had previously received at least two different PI-based regimens and who initiated darunavir (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters were calculated for each subject. Seventy-nine percent of subjects had a viral load <50 copies/mL at 48 weeks. The only subject with two consecutive viral loads >50 copies/mL at the end of the study period was the patient with the lowest instantaneous inhibitory potential (IIP). The sample size was insufficient to show an association between any of the PK/PD parameters and virologic response. Based on our observations, we suggest that the utility of IIP for antiretroviral combinations for the prediction of virologic outcome in HIV-1 drug-experienced patients should be studied further.