Most patients fail second-line antiretroviral therapy (ART) owing to poor adherence rather than resistance.
Predictors of protease inhibitor (PI) resistance in patients with second-line virological failure (VF) are needed.
We found random lopinavir (LPV) concentrations to be the strongest predictor of PI resistance.
Other factors associated with PI resistance were male sex and duration on LPV.
Genotype antiretroviral resistance testing could be limited to patients in VF with random LPV concentrations ≥1 µg/mL.