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| Figure 2: Progress of resistance selection and and emergence of resistance mutations selected in vitro in the presence of GS-9224. The EC50 and CC50 values of GS- 9224 in MT-2 cells are indicated by the red and blue lines respectively. Each closed black circle represents one passage of the infected cell culture. Viral passages 3, 4, 5, 6 and 7 are denoted as P3, P4, P5, P6 and P7 and represent a transfer of cell-free virus supernatant to fresh uninfected cell culture with a doubling of the drug concentration. The culture supernatant from the last infected cell culture before the increase of inhibitor concentration (red circle) was used for population sequencing and the mutations identified in the integrase region are indicated. In addition, P4 and P6 viral pools were used for clonal sequencing to determine the percentage of clones containing each identified mutation. P4 virus: L74M (62%), G140S (62%); P6 virus: L74M (100%), G140S (100%), Q148K (93.3%). |
