The nonnucleoside reverse transcriptase inhibitors (NNRTI) have low genetic barriers to resistance. Resistance can sometimes be overcome by increasing drug exposure. We assessed factors associated with 48-week virological response in treatment-experienced individuals receiving NNRTI therapy including resistance testing results and plasma drug exposure. Of 62 individuals assigned a new NNRTI-based regimen following resistance testing therapy consisted of efavirenz in 35 (56%) and nevirapine in 27 (44%) individuals. NNRTI fold change (FC) was determined from resistance test at baseline and plasma drug concentration at week 4. Mean time weighted change from baseline VL was -0.68 log over 48 weeks. Significant associations with change front baseline VL included baseline VL and FC whereas plasma drug concentration was not associated. In this cohort of highly treatment-experienced individuals treated with NNRTI regimens, we did not observe a significant association between NNRTI plasma concentration and virological response.