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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).