FIG 3.

Sensitivity to CCR5 antagonists. Comparison of maraviroc (MVC) (A and D) and TAK-779 (B and E) sensitivity of Env-pseudotyped viruses derived from historical patients (HP; n = 10), intermediate patients (IP; n = 15), and contemporary patients (CP; n = 13) in TZM-bl cells. Scatter dot plots show the distributions of MVC and TAK-779 IC₅₀s (A and B) and maximal percent inhibition (MPI) values (D and E) for pseudotypes of each period. (C) Correlation between MVC and TAK-779 IC₅₀s. (F) Correlation between MVC and TAK-779 MPIs. (G) Comparison of TAK-779 MPIs in Affinofile cells in the presence of 6 μM or 12 μM of TAK-779. A panel of 15 pseudotyped viruses (5 HP, 5 IP, and 5 CP) that presented a range of sensitivities to this inhibitor was used to confirm that the concentration of TAK-779 was saturating. There was no difference in inhibition of infection between 6 μM and 12 μM, indicating that 6 μM was saturating in Affinofile cells expressing a high level of CCR5 (P = 0.50 by paired t test). (H) Comparison of TAK-779 sensitivity of Env-pseudotyped viruses derived from HP, IP, and CP in Affinofile cells. Scatter dot plots show the distributions of TAK-779 MPI values for pseudotypes of each period. Differences between viruses over calendar time were evaluated using a Jonckheere-Terpstra test. (I) Correlation between enfuvirtide IC₅₀s and TAK-779 MPIs. Comparison of infectivity of Env pseudotypes from HP, IP, and CP in Affinofile cells expressing low levels (J) or high levels (K) of CCR5, after normalization for Env content (1 ng).