Development of resistance to 5P12-RANTES (5P12).
A. Weekly increases in p24 capsid antigen during four successive rounds of selection: 5P12 1 (blue, weeks 1–15); 5P12 2 (green, weeks 13–25); 5P12 3 (purple, weeks 24–33); and 5P12 4 (brown, weeks 30–44). Control cultures with no inhibitor are shown in black filled circles. B. Increasing concentrations of 5P12 expressed as multiples of the 90% inhibitory concentration (IC90 = 0.12 nM) for each of the four rounds of selection, with colors matching panel A. C. Replication of viruses from indicated weeks of selection on activated CD4+ T cells from a CCR5Δ32 homozygous donor. Values are mean p24 capsid antigen levels (± SE of triplicate cultures) after 7 days of culture. D. Viruses from the indicated weeks of 5P12-RANTES round 4 of selection (5P12 4) or control cultures with no inhibitors were used to infect activated CD4+ T cells from normal donors in the presence of the CXCR4 blocking agent AMD3100 (AMD). The percent inhibition by AMD3100 of p24 capsid antigen levels after 7 days of culture is plotted versus the week of virus isolation.