Table 1. Virological parameters of 12 HIV-infected individuals participating in the GS-US-183-0105 study of elvitegravir.
Major Mutations in INTa | EC50 FC INSTI | EC50 FC PI | EC50 FC NNRTI | EC50 FC NRTI | |||||||||||||||||||||||||||
Patient | HIV-1 RNAb | E92 | N155 | Q148 | PI (1) | PI (2) | #TAMs | #NAMs | NNRTI (1) | EVG | RAL | APV | TPV | RTV | IDV | NFV | DRV | SQV | LPV | ATV | EFV | NVP | ETR | DLV | AZT | ABC | 3TC | FTC | d4T | TFV | ddI |
08–175 | 4.75 | 5 | 5 | 5 | 7 | 2 | 17 | 0.9 | 17 | 0.8 | MAX | 7.6 | 34 | 6.0 | 67 | 32 | 44 | MAX | 133 | 6.5 | 210 | 4.2 | 12 | MAX | MAX | 4.0 | 1.5 | 2.2 | |||
08–172 | 4.77 | E92E/Q | 6 | 4 | 5 | 7 | 3 | 3.0 | 0.7 | 37 | 3.2 | MAX | 19 | 369 | 7.4 | MAX | MAX | 239 | MAX | MAX | 22 | 6.5 | 88 | 12 | 211 | MAX | 23 | 9.1 | 5.5 | ||
08–198 | 5.58 | E92E/Q | 0 | 3 | 1 | 2 | 0 | 1.2 | 1.4 | 0.9 | 0.7 | 3.4 | 0.6 | 2.1 | 0.8 | 2.7 | 2.9 | 2.0 | 2.8 | 3.1 | 0.7 | 3.1 | 6.2 | 1.8 | 5.1 | 15 | 2.9 | 2.2 | 0.7 | ||
08–183 | 5.24 | E92Q | 3 | 4 | 5 | 6 | 0 | 7.8 | 2.3 | 3.2 | 1.8 | 7.8 | 3.3 | 54 | 1.6 | 30 | 21 | 45 | 8.6 | 5.8 | 0.9 | 1.0 | 9.3 | 7.5 | 267 | MAX | 3.4 | 5.5 | 4.6 | ||
08–180 | 5.43 | E92Q | 8 | 6 | 4 | 6 | 0 | 37 | 1.9 | MAX | 1.8 | MAX | 4.5 | MAX | MAX | 66 | MAX | MAX | 6.5 | 4.8 | 0.7 | 1.5 | 40 | 4.9 | MAX | MAX | 5.0 | 5.5 | 3.8 | ||
08–177 | 5.03 | N155N/H | 7 | 5 | 4 | 6 | 2 | 29 | 2.2 | 45 | 1.3 | MAX | 16 | 126 | 19 | 19 | MAX | 65 | 44 | MAX | 475 | 29 | 19 | 5.7 | 166 | 317 | 14 | 7.1 | 2.9 | ||
08–194 | 5.66 | N155H | 3 | 5 | 2 | 4 | 1 | 49 | 2.6 | 35 | 2.5 | 129 | 4.2 | 25 | 2.7 | 8.8 | 15 | 7.8 | 9.2 | 5.8 | 1.5 | 0.5 | 5.6 | 5.5 | MAX | MAX | 2.9 | 1.4 | 3.4 | ||
08–201 | 5.75 | N155H | 3 | 2 | 0 | 1 | 0 | 128 | 3.2 | 2.9 | 0.9 | 7.6 | 2.0 | 14 | 1.0 | 0.9 | 4.9 | 1.0 | 2.6 | 1.6 | 1.3 | 0.5 | 1.0 | 3.4 | MAX | MAX | 1.6 | 0.8 | 1.4 | ||
08–202 | 5.33 | E92E/Q | N155N/H | 4 | 2 | 2 | 2 | 1 | 4.2 | 1.2 | 0.8 | 0.5 | 5.1 | 1.5 | 13 | 0.7 | 1.8 | 0.2 | 1.3 | MAX | MAX | 0.3 | 19 | 13 | 2.0 | 0.6 | 0.9 | 3.6 | 4.9 | 1.1 | |
08–230 | 4.55 | E92Q | N155H | 4 | 10 | 5 | 7 | 1 | 492 | 18 | 18 | 2.7 | MAX | MAX | MAX | 3.3 | MAX | MAX | MAX | 65 | 30 | 0.5 | 47 | 18 | 9.0 | MAX | MAX | 3.8 | 4.4 | 2.4 | |
08–189 | 5.76 | Q148R | 2 | 2 | 3 | 4 | 0 | 35 | 2.3 | 5.8 | 1.4 | 13 | 17 | 38 | 1.2 | 1.0 | 7.5 | 13 | 1.6 | 4.5 | 0.5 | 0.6 | 18 | 7.6 | 244 | 161 | 19 | 10 | 3.2 | ||
08–182 | 5.50 | Q148R | 3 | 0 | 0 | 3 | 2 | 179 | 5.4 | 66 | 0.6 | 8.8 | 1.1 | 7.7 | 7.8 | 3.8 | 7.8 | 9.2 | MAX | MAX | 293 | 133 | 1.9 | 13 | MAX | MAX | 7.2 | 2.9 | 8.4 |
Plasma viral load (log10 copies/ml). INSTI-R, mutations associated with resistance to INSTI; PI (1), number of primary mutations associated with resistance to PI; PI (2), number of secondary mutations associated with resistance to PI; #TAMs, number of thymidine analogue-associated mutations; #NAMs, number of nucleoside analogue-associated mutations; NNRTI (1), number of primary mutations associated with resistance to NNRTI. EC50 FC, based on VIRALARTS [49] three independent EC50 replicates for each drug were used to calculate the fold changes (FC) of the query viruses relative to the HIV-1NL4-3 control and the mean EC50 FC is indicated. MAX, complete virus inhibition was not achieved using the maximum drug concentration, i.e., virus was completely resistant to the respective antiretroviral drug. Virus 08-175 contained the INSTI-resistance mutations T66A and S147G.