Clinically Relevant Interpretation of Genotype and Relationship to Plasma Drug Concentrations for Resistance to Saquinavir-Ritonavir in Human Immunodeficiency Virus Type 1 Protease Inhibitor-Experienced Patients

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Abstract
It has been shown that virological protease inhibitor (PI) resistance mutations present at the initiation of saquinavir (SQV) plus ritonavir (RTV) therapy in PI-experienced patients are the strongest predictors of virological response. But most of the current resistance algorithms are adapted for unboosted SQV regimens. We applied a stepwise methodology for the development and validation of a clinically relevant genotypic resistance score for an SQV (800 mg twice per day [b.i.d.]) plus RTV (100 mg b.i.d.)-containing regimen. PI-experienced patients treated by this regimen achieved a human immunodeficiency virus plasma viral load (VL) of 10 and −1.23 log 10 copies/ml of VL reduction, respectively, while it was −0.27 log 10 copies/ml for those with at least two mutations, classifying the isolates as “no evidence of resistance” (0 or 1 mutation) or “resistance ” (≥2 mutations). The minimum concentration in plasma ( C min ) of SQV alone was not associated with the virological response. However, the combination of the SQV C min and the genotypic score, expressed as the genotypic inhibitory quotient, was predictive of the virological response, suggesting that the interpretation of SQV concentrations in plasma should be done only in the context of the resistance index provided by viral genotype for PI-experienced patients.