Resistance Mutations in the Protease of drug-naive and drug-treated individuals.

250 samples from 234 drug-naive patients and 115 samples from 78 treated A/AE patients were genotyped. 31 patients were sampled both prior to treatment and after treatment failure. PI mutations found in all A/AE naive patients were compared to those found in A/AE drug-treated ones and to samples from 254 drug naive and 60 drug treated B individuals diagnosed since 2001. The first available sample from each drug-naive individual was used for analysis. For mutation-frequency analysis of drug-treated patients each mutation was counted once. Only mutations showing statistically significant differences between drug-naive and drug-treated patients and/or between A/AE and B frequencies are included.Mutations in the Protease: The PI mutations L23I, L24I, D30N, V32I, M46I/L, I47A, G48V, I50L/V, I54V, V82A/S, I84V/A/C, N88S/T and L90M were considered major mutations. Secondary PI mutations included L10V/I/F/M, K20R, L33F, M36I, F53L, A71V/I and G73S/T/C/A.N – NRTIs; NN – NNRTIs; NNRTIs – Non-nucleosides reverse transcriptase inhibitors; NS – Not significant; NRTIs – Nucleosides reverse transcriptase inhibitors; PI – Protease inhibitors;aSubtyping was performed using the Stanford Database Rapid Subtyping Tool [23]–[24]. According to that classification 192 patients had virus containing protease of subtype A and RT most similar to CRF01_AE; for 70 both the protease and the RT were CRF01_AE; 52 were of subtype A; and four had protease classified as CRF01_AE and RT classified as A. Other subtyping tools such as Geno2Pheno (http://www.geno2pheno.org/) or the Rega Subtyping Tool (http://jose.med.kuleuven.be/subtypetool/html/) [57] vary to some extent in the classification of variants.