TABLE 2.
Competition condition and genotype of competing viruses | RF (1 + s) valuea | P valuec | Fitness interpretation |
---|---|---|---|
Without drug | |||
WT vs WTb | 1.02 ± 0.04 | WT = WT | |
WT vs RT-M184V | 0.90 ± 0.02 | <0.001 | WT > RT-M184V |
WT vs IN-E92Q | 0.86 ± 0.04 | <0.001 | WT > IN-E92Q |
WT vs RT-M184V + IN-E92Q | 0.79 ± 0.02 | <0.001 | WT > RT-M184V + IN-E92Q |
WT vs RT-K65R | 0.70 ± 0.04 | <0.001 | WT > RT-K65R |
WT vs RT-K65R/M184V | 0.67 ± 0.08 | <0.001 | WT > RT-K65R/M184V |
WT vs RT-K65R/M184V + IN-E92Q | <0.56 ± 0.02 | <0.001 | WT > RT-K65R/M184V + IN-E92Q |
IN-E92Q vs RT-M184V | 1.13 ± 0.09 | 0.046 | IN-E92Q < RT-M184V |
RT-M184V vs RT-M184V + IN-E92Q | 0.83 ± 0.07 | 0.002 | RT-M184V > RT-M184V + IN-E92Q |
IN-E92Q vs RT-M184V + IN-E92Q | 0.90 ± 0.02 | 0.004 | IN-E92Q > RT-M184V + IN-E92Q |
IN-E92Q vs RT-K65R/M184V + IN-E92Q | 0.64 ± 0.02 | <0.001 | IN-E92Q > RT-K65R/M184V + IN-E92Q |
RT-M184V vs RT-K65R | 0.78 ± 0.02 | <0.001 | RT-M184V > RT-K65R |
RT-K65R/M184V vs RT-K65R | 1.32 ± 0.2 | 0.014 | RT-K65R/M184V < RT-K65R |
With drug | |||
WT vs IN-E92Q (0.25 nM EVG) | 0.87 ± 0.07 | 0.008 | WT > IN-E92Q |
WT vs IN-E92Q (0.5 nM EVG) | 0.96 ± 0.02 | 0.082 | WT ≈ IN-E92Q |
WT vs IN-E92Q (1 nM EVG) | 1.08 ± 0.6 | 0.170 | WT ≤ IN-E92Q |
WT vs RT-M184V (1 nM FTC) | 0.90 ± 0.02 | 0.003 | WT > RT-M184V |
WT vs RT-M184V (10 nM FTC) | 0.98 ± 0.02 | 0.172 | WT ≈ RT-M184V |
WT vs RT-M184V (100 nM FTC) | 1.25 ± 0.11 | 0.004 | WT < RT-M184V |
IN-E92Q vs RT-M184V + IN-E92Q (1 nM EVG) | 0.86 ± 0.08 | 0.009 | IN-E92Q > RT-M184V + IN-E92Q |
IN-E92Q vs RT-M184V + IN-E92Q (100 nM EVG) | 0.88 ± 0.1 | 0.048 | IN-E92Q > RT-M184V + IN-E92Q |
IN-E92Q vs RT-K65R/M184V + IN-E92Q (1 nM EVG) | 0.67 ± 0.005 | <0.001 | IN-E92Q > RT-K65R/M184V + IN-E92Q |
IN-E92Q vs RT-K65R/M184V + IN-E92Q (100 nM EVG) | 0.74 ± 0.2 | 0.007 | IN-E92Q > RT-K65R/M184V + IN-E92Q |
IN-E92Q vs RT-M184V + IN-E92Q (1 nM EVG, 1 nM FTC) | 0.92 ± 0.08 | 0.050 | IN-E92Q ≥ RT-M184V + IN-E92Q |
IN-E92Q vs RT-M184V + IN-E92Q (100 nM EVG, 100 nM FTC) | 1.19 ± 0.04 | 0.002 | IN-E92Q < RT-M184V + IN-E92Q |
IN-E92Q vs RT-K65R/M184V + IN-E92Q (1 nM EVG, 1 nM FTC) | 0.78 ± 0.18 | 0.024 | IN-E92Q > RT-K65R/M184V + IN-E92Q |
IN-E92Q vs RT-K65R/M184V + IN-E92Q (100 nM EVG, 100 nM FTC) | 1.21 ± 0.19 | 0.076 | IN-E92Q ≤ RT-K65R/M184V + IN-E92Q |
RT-M184V vs RT-M184V + IN-E92Q (0.25 nM EVG, 1 nM FTC) | 0.94 ± 0.06 | 0.066 | RT-M184V ≥ RT-M184V + IN-E92Q |
RT-M184V vs RT-M184V + IN-E92Q (5 nM EVG, 100 nM FTC) | 1.54 ± 0.13 | <0.001 | RT-M184V < RT-M184V + IN-E92Q |
RT-M184V vs RT-K65R/M184V + IN-E92Q (0.25 nM EVG, 1 nM FTC) | 0.74 ± 0.09 | 0.001 | RT-M184V > RT-K65R/M184V + IN-E92Q |
RT-M184V vs RT-K65R/M184V + IN-E92Q (5 nM EVG, 100 nM FTC) | 1.23 ± 0.2 | 0.054 | RT-M184V ≤ RT-K65R/M184V + IN-E92Q |
The relative fitness (RF) value of the mutant in competition with wild-type HIV-1 was calculated as follows: (1 + s) = exp{(1/t) × ln[(Mt/Wt) × (Wt0/Mt0)]}, where s is the selection coefficient; t is time (in days); Mt and Mt0 are the fractions of mutant virus initially and at the time of measurement, respectively; and Wt and Wt0 are the fractions of wild-type virus initially and at the time of measurement, respectively (29). Mutant-versus-mutant competitions were analyzed using the same equation. A 1 + s value of 1.00 represents equivalent levels of viral fitness between the competitors; a value of <1.00 represents growth less efficient than that of the competitor. The data shown represent the means and standard deviations from at least 3 independent experiments.
A control experiment was performed to verify that isogenic HIV-1 recombinants differing only in their sequence tags would grow with equivalent fitness. WT, wild type.
P values were determined using a two-tailed Student's t test comparing the competitions to the wild-type-versus-wild-type competition.