Fig. 5: LEN resistance and infectivity of M66I-carrying variants.

a LEN dose–response analysis of cloned mutant viruses carrying either Q67N or M66I + Q67N. Infectivity of VSV-G-pseudotyped viruses in MT-4 cells was measured across increasing concentrations of lenacapavir and normalized to the maximum infectivity of each virus. One representative result from two independent experiments is shown. b Effects of low-level LEN DRMs on M66I infectivity. Relative infectivity of variants carrying M66I along with different LEN DRMs was assessed by infecting TZM-bl cells. Luciferase activity was normalized to viral input, as determined by levels of virion-associated RT. Infections were performed in triplicate and repeated twice, with six data points shown (n = 6). Data are represented as the mean with error bars representing the standard error of the mean (SEM). Statistical analysis was conducted using one-way ANOVA followed by Dunnett’s multiple comparisons test to calculate adjusted p values comparing M66I to the other mutants. ****p < 0.0001; **p < 0.01; *p < 0.05. c LEN dose–response analysis of the M66I single mutant and double mutants carrying M66I in combination with Q67H, Q67N, or A105T, performed as described in (a). Shown are the average values with error bars denoting SEM from multiple experiments: n = 4 for M66I and M66I + Q67H, and n = 3 for M66I + Q67N. For M66I + A105T (n = 2), data are shown without error bars and no statistical comparisons were performed. Comparison of dose–response curves using the extra sum-of-squares F test revealed a statistically significant difference among the three datasets (M66I, M66I + Q67H, and M66I + Q67N). Source data are provided as a Source data file.