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Table 2 Novel non-nucleoside RT inhibitor resistance associated mutations

From: Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance associated mutations

    Site-directed Mutantsa LDA 3Fb
Mutation c N wt d N mut e NVP EFV ETR max( F 1) max( n 11 ) f max n 1 1 n 1 1 + n 0 1 g min( cutoff ) h
V179 M 67699 31 0.8-2.3 0.3-0.4 0.4-0.9 0.327 (EFV) 13 (ETR) 8/(8 + 10) (EFV) 1.35 (ETR)
H221 L 76783 31 4.2-5.0 1.5-1.6 1.1 0.118 (EFV) 2 (EFV) 2/(2 + 1) (EFV) 2.03 (ETR)
V179 Y 67699 17 0.2-0.5 < 0.2-0.2 < 0.1-0.2 0.063 (ETR) 16 (ETR) 16/(16 + 472) (ETR) 1.44 (ETR)
K219H 67913 129 1.3-2.2 1.0-1.8 1.1-1.8 0.047 (ETR) 14 (ETR) 14/(14 + 447) (ETR) 1.45 (ETR)
K219D 67913 161 1.4-3.8 1.3-2.2 0.4-2.0 0.044 (ETR) 24 (ETR) 24/(24 + 894) (ETR) 1.22 (ETR)
V179 N 67699 15 1.2-1.9 0.9-1.2 0.6-0.8 0.039 (ETR) 8 (ETR) 8/(8 + 391) (ETR) 1.50 (ETR)
T376S 15617 7415 2.8-3.4 1.5-2.0 1.6-2.1 0.035 (EFV) 135 (EFV) 135/(135 + 145) (EFV) 1.67 (ETR)
Y181S 72643 3 NA NA NA 0.019 (ETR) 3 (ETR) 3/(3 + 310) (ETR) 1.45 (ETR)
L100 V 77197 8 6.4 (1) 9.0-18.3 (2) 1.1-1.2 (2) 0.017 (ETR) 6 (ETR) 6/(6 + 678) (ETR) 1.63 (ETR)
Y181 F 72643 9 1.1-2.0 0.4-0.8 0.4-0.7 0.016 (ETR) 4 (ETR) 4/(4 + 503) (ETR) 1.33 (ETR)
K102L 72791 12 2.3-2.9 0.5-1.2 0.3-0.4 0.015 (ETR) 4 (ETR) 4/(4 + 505) (ETR) 1.77 (ETR)
K101 N 72175 94 5.0 (1) 2.8 (1) 0.8 (1) 0.015 (ETR) 4 (ETR) 4/(4 + 434) (ETR) 1.66 (ETR)
V106 L 75529 44 0.5-0.6 0.7-1.1 0.2-0.3 0.015 (ETR) 5 (ETR) 5/(5 + 617) (ETR) 1.69 (ETR)
E138 A 75869 1828 2.2-4.9 1.2- 3.6 2.8- 3.5 0.014 (ETR) 14 (ETR) 14/(14 + 157) (ETR) 2.10 (ETR)
M357T 44115 17866 0.9 (1) 1.2 (1) NA 0.013 (ETR) 117 (ETR) 117/(117 + 199) (ETR) 1.88 (ETR)
T139R 76899 243 6.4-7.3 1.5-2.7 1.0-1.2 0.010 (ETR) 2 (ETR) 2/(2 + 137) (ETR) 2.22 (ETR)
E370G 75915 489 NA NA NA 0.007 (ETR) 2 (ETR) 1/(1 + 1) (EFV) 2.38 (ETR)
I135T 45829 18410 NA NA NA 0.006 (ETR) 52 (ETR) 52/(52 + 94) (ETR) 2.16 (ETR)
L234I 79037 98 0.6-1.0 1.6-2.3 0.9-1.1 0.004 (ETR) 1 (ETR) 1/(1 + 353) (ETR) 1.95 (ETR)
S379C 69973 3578 NA NA NA 0.001 (ETR) 1 (ETR) 1/(1 + 1) (ETR) 3.35 (ETR)
R206I 79051 8 1.0-1.7 0.4-0.7 0.5-0.9 NA 0 (ETR) 0/(0 + 102) (ETR) 2.33 (ETR)
S134N 79041 19 1.2-2.1 0.6-0.7 0.8-0.9 NA 0 (ETR) 0/(0 + 69) (ETR) 2.45 (ETR)
H221 C 76783 59 NA NA NA NA 0 (ETR) 0/(0 + 20) (ETR) 2.73 (ETR)
I382T 78025 329 2.4- 6.7 0.9-1.7 0.7-2.4 NA 0 (ETR) 0/(0 + 2) (ETR) 3.30 (ETR)
D237E 78246 423 NA NA NA NA 0 (EFV) 0/(0 + 3) (EFV) 3.67 (ETR)
N348T 74372 170 NA NA NA NA 0 (ETR) 0/(0 + 0) (ETR) 4.05 (ETR)
E399G 66049 670 NA NA NA NA 0 (ETR) 0/(0 + 0) (ETR) 4.10 (ETR)
G190 T 72912 10 > 67.4 7.8-14.9 0.6-0.7 NA 0 (EFV) 0/(0 + 2) (EFV) 4.16 (ETR)
Y188 F 76892 41 1.4-1.9 0.3-0.5 0.2-0.6 NA 0 (NVP) 0/(0 + 0) (NVP) 4.70 (NVP)
L283I 72462 5930 NA NA NA NA 0 (ETR) 0/(0 + 0) (ETR) 5.01 (ETR)
K101 A 72175 50 8.8-13.4 4.1-5.6 1.5-1.8 NA 0 (EFV) 0/(0 + 3) (EFV) 5.04 (NVP)
K101 D 72175 7 13.3-18.9 5.7-6.8 1.0-1.3 NA 0 (EFV) 0/(0 + 3) (EFV) 5.08 (EFV)
T139K 76899 348 4.4-5.8 1.2-2.3 2.4-3.0 NA 0 (ETR) 0/(0 + 0) (ETR) 5.10 (ETR)
T165L 75078 183 NA NA NA NA 0 (ETR) 0/(0 + 0) (ETR) 5.81 (ETR)
T386A 59810 1756 NA 1.6 (1) 0.5 (1) NA 0 (NVP) 0/(0 + 0) (NVP) 6.07 (NVP)
V241M 78771 23 4.7-5.6 1.0-1.8 0.8-1.2 NA 0 (NVP) 0/(0 + 0) (NVP) 6.90 (NVP)
I382L 78025 228 NA NA NA NA 0 (NVP) 0/(0 + 0) (NVP) 7.30 (NVP)
G335S 65035 1877 NA NA NA NA 0 (ETR) 0/(0 + 0) (ETR) 7.55 (ETR)
E399D 66049 10697 NA NA NA NA 0 (ETR) 0/(0 + 0) (ETR) 7.98 (ETR)
R358K 70517 5995 NA NA NA NA 0 (NVP) 0/(0 + 0) (NVP) 8.06 (NVP)
  1. aFold-Change range from 3 measurements, unless otherwise indicated between brackets.
  2. FC > Biological Cut-Off (BCO) in bold, FC ≤ BCO in italic; BCO for NVP is 6.0, BCO for EFV is 3.3 and BCO for ETR is 3.2.
  3. bSummarized for the three non-nucleoside RT inhibitors (NNRTI).
  4. cTop 40 mutations, ranked by max(LDA F1) descending, then by min(LDA cutoff) ascending. Mutations shown are from the list of 124 NNRTI mutations with RWF ≥ 0 and LDA cutoff > 0 for NVP, EFV and ETR. Known NNRTI positions or novel mutations listed in [32, 33] are shown in bold.
  5. dFrequency of wild-type (not within a mixture) in LDA data set.
  6. eFrequency of mutation (not within a mixture) in LDA data set.
  7. fn11 is the number of samples with amino acid mutation having a predicted phenotype above the LDA cutoff.
  8. gn01 is the number of samples with wild type amino acid having a predicted phenotype above the LDA cutoff.
  9. hCutoff in log Fold-Change (taking the wild-type and mutation frequency percentages as prior probabilities in the LDA can result in cutoff values outside of the range of the predicted phenotypes).