FIG. 2.

Effect of CN mutations from treatment-experienced patients' RTs on NNRTI resistance. (A to D) IC₅₀ determinations for the viruses containing CN mutations from treatment-experienced patients' RTs in the context of their own pol to NVP (A), DLV (B), EFV (C), ETR (D). White bars represent the average IC₅₀ for the wild-type RT control; gray bars represent RTs containing pol domains originated from the patients' virus; black bars represent both pol and CN originated from the patients' virus. Numbers in front of black bars represent fold changes, and asterisks within the black bars indicate a statistically significant difference in IC₅₀ within each pair of RTs connected by a bracket (t test, P < 0.05). Numbers within bars represent the maximum drug concentration used for the testing that was not sufficient to inhibit viral replication. (E and F) IC₅₀ determinations for the viruses containing specific CN mutation(s) from treatment-experienced patients' RTs to NVP (E) and EFV (F). Numbers in front of gray bars represent fold changes, and asterisks within the gray bars indicate a statistically significant difference in IC₅₀ versus the black bar for each group connected by a bracket (t test, P < 0.05). Direction of arrow located near the number indicates a decrease or increase in resistance caused by mutation. An additional asterisk within the bar indicates a statistically significant change in resistance for the double mutant versus the single mutant within the group (t test, P < 0.05). Schematics of the corresponding RT structures are depicted on the left-hand side of panels A, B, C, D (top part), and E and F (bottom part). Groups of constructs are connected by a bracket. White boxes in schematics represent the wild-type sequences, and gray boxes represent the patients' RT sequences; white strips within the gray box indicate the reversion of the mutant amino acid to the wild type; gray strips within the white box indicate a replacement of the wild-type amino acid to the mutant amino acid. Specific mutations are shown near each construct where applicable, designating either the reversion of this mutation to the wild-type amino acid (e.g., ×360I) or the reversion of the wild-type amino-acid to the mutant amino acid (e.g., +348I). Linear regression analysis of resistance changes to AZT versus NVP (G), and to AZT versus EFV (H) caused by CN mutations from treatment-experienced patients. Resistance data for NVP and EFV are collected from Fig. 1A and panels A, C, E, and F of this figure and, for AZT, from reports by Delviks-Frankenberry et al. (12) and Nikolenko et al. (34). The correlation coefficients (R) were determined using SigmaPlot 8.0 software. Fold resistance was calculated as a ratio between IC₅₀s for virus containing specific mutation(s) and correspondent control virus without this mutation(s).