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. 2015 May 14;59(6):3441–3449. doi: 10.1128/AAC.00040-15

TABLE 2.

Relative fitness of wild-type and site-directed mutant HIV-1 in growth competition assays

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
a

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.

b

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.

c

P values were determined using a two-tailed Student's t test comparing the competitions to the wild-type-versus-wild-type competition.