Drug (ID: DG00269) and It's Reported Resistant Information
Name
Rilpivirine
Synonyms
500287-72-9; TMC278; Edurant; TMC 278; UNII-FI96A8X663; R278474; TMC-278; 4-{[4-({4-[(E)-2-Cyanoethenyl]-2,6-Dimethylphenyl}amino)pyrimidin-2-Yl]amino}benzonitrile; CHEBI:68606; FI96A8X663; R 278474; 4-{[4-({4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile; (E)-4-((4-((4-(2-cyanovinyl)-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile; (E)-4-(4-(4-(2-cyanovinyl)-2,6-dimethylphenylamino)pyrimidin-2-ylamino)benzonitrile; W-202888; RPV; Mu O-conotoxin
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Indication
In total 2 Indication(s)
Human immunodeficiency virus disease [ICD-11: 1C60-1C62]
Approved
[1]
Pain [ICD-11: MG30]
Investigative
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
HIV infection [ICD-11: 1C62]
[2]
Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
HIV infection [ICD-11: 1C62]
[1]
Target Human immunodeficiency virus Reverse transcriptase (HIV RT) POL_HV1B1 [1]
Voltage-gated sodium channel alpha Nav1.8 (SCN10A) SCNAA_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C22H18N6
IsoSMILES
CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)/C=C/C#N
InChI
1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+
InChIKey
YIBOMRUWOWDFLG-ONEGZZNKSA-N
PubChem CID
6451164
ChEBI ID
CHEBI:68606
TTD Drug ID
D0T6WN
DrugBank ID
DB08864
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-01: Infectious/parasitic diseases
Click to Show/Hide the Resistance Disease of This Class
HIV infection [ICD-11: 1C62]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.S48T+p.V90VI+p.K101E+p.Y115YF+p.Y181YC+p.M184I+p.R211N+p.K219KE+p.V245N+p.L283I+p.V292I+p.I293V
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.992
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.67
TM score: 0.96321
Amino acid change:
S48T+V90I+K101E+Y115F+Y181C+M184I+R211N+K219E+V245N+L283I+V292I+I293V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.L74V+p.L100I+p.K103N+p.M184V+p.Q207A+p.R211K+p.P225H+p.I293V
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.928
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.86
TM score: 0.95495
Amino acid change:
V35I+L74V+L100I+K103N+M184V+Q207A+R211K+P225H+I293V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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260
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L
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270
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280
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310
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L
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V
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G
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Y
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320
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330
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340
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350
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K
K
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A
A
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360
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A
A
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H
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N
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L
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370
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E
E
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A
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T
T
T
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380
|
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V
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K
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K
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390
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K
K
L
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I
Q
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K
K
E
E
T
T
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400
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T
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W
W
W
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T
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E
Y
Y
W
W
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A
A
T
T
410
|
W
W
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I
P
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E
W
W
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V
N
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420
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P
P
P
P
L
L
V
V
K
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L
L
W
W
Y
Y
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L
L
430
|
E
E
K
K
E
E
P
P
I
I
V
V
G
G
A
A
E
E
T
T
440
|
F
F
Y
Y
V
V
D
D
G
G
A
A
A
A
N
N
R
R
E
E
450
|
T
T
K
K
L
L
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
460
|
N
N
R
R
G
G
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
470
|
T
T
D
D
T
T
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
480
|
Q
Q
A
A
I
I
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
490
|
G
G
L
L
E
E
V
V
N
N
I
I
V
V
T
T
D
D
S
S
500
|
Q
Q
Y
Y
A
A
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
510
|
P
P
D
D
Q
Q
S
S
E
E
S
S
E
E
L
L
V
V
N
N
520
|
Q
Q
I
I
I
I
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
530
|
K
K
V
V
Y
Y
L
L
A
A
W
W
V
V
P
P
A
A
H
H
540
|
K
K
G
G
I
I
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
550
|
K
K
L
L
V
V
S
S
A
A
G
G
I
I
R
R
K
K
V
V
560
|
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V60I+p.K103N+p.D123E+p.I142V+p.Y181C+p.G196E+p.T200A+p.R211K+p.K219E+p.I293IM
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.998
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.96512
Amino acid change:
K20R+V60I+K103N+D123E+I142V+Y181C+G196E+T200A+R211K+K219E+I293M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
S
S
P
P
I
I
E
E
T
T
V
V
P
P
10
|
V
V
K
K
L
L
K
K
P
P
G
G
M
M
D
D
G
G
P
P
20
|
K
R
V
V
K
K
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
30
|
K
K
I
I
K
K
A
A
L
L
V
V
E
E
I
I
C
C
T
T
40
|
E
E
M
M
E
E
K
K
E
E
G
G
K
K
I
I
S
S
K
K
50
|
I
I
G
G
P
P
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
60
|
V
I
F
F
A
A
I
I
K
K
K
K
K
K
D
D
S
S
T
T
70
|
K
K
W
W
R
R
K
K
L
L
V
V
D
D
F
F
R
R
E
E
80
|
L
L
N
N
K
K
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
90
|
V
V
Q
Q
L
L
G
G
I
I
P
P
H
H
P
P
A
A
G
G
100
|
L
L
K
K
K
K
K
N
K
K
S
S
V
V
T
T
V
V
L
L
110
|
D
D
V
V
G
G
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
120
|
L
L
D
D
E
E
D
E
F
F
R
R
K
K
Y
Y
T
T
A
A
130
|
F
F
T
T
I
I
P
P
S
S
I
I
N
N
N
N
E
E
T
T
140
|
P
P
G
G
I
V
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
150
|
P
P
Q
Q
G
G
W
W
K
K
G
G
S
S
P
P
A
A
I
I
160
|
F
F
Q
Q
S
S
S
S
M
M
T
T
K
K
I
I
L
L
E
E
170
|
P
P
F
F
R
R
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
180
|
I
I
Y
C
Q
Q
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
190
|
G
G
S
S
D
D
L
L
E
E
I
I
G
E
Q
Q
H
H
R
R
200
|
T
A
K
K
I
I
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
210
|
L
L
R
K
W
W
G
G
L
L
T
T
T
T
P
P
D
D
K
E
220
|
K
K
H
H
Q
Q
K
K
E
E
P
P
P
P
F
F
L
L
W
W
230
|
M
M
G
G
Y
Y
E
E
L
L
H
H
P
P
D
D
K
K
W
W
240
|
T
T
V
V
Q
Q
P
P
I
I
V
V
L
L
P
P
E
E
K
K
250
|
D
D
S
S
W
W
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
260
|
L
L
V
V
G
G
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
270
|
I
I
Y
Y
P
P
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
280
|
C
C
K
K
L
L
L
L
R
R
G
G
T
T
K
K
A
A
L
L
290
|
T
T
E
E
V
V
I
M
P
P
L
L
T
T
E
E
E
E
A
A
300
|
E
E
L
L
E
E
L
L
A
A
E
E
N
N
R
R
E
E
I
I
310
|
L
L
K
K
E
E
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
320
|
D
D
P
P
S
S
K
K
D
D
L
L
I
I
A
A
E
E
I
I
330
|
Q
Q
K
K
Q
Q
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
340
|
Q
Q
I
I
Y
Y
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
350
|
K
K
T
T
G
G
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
360
|
A
A
H
H
T
T
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
370
|
E
E
A
A
V
V
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
380
|
I
I
V
V
I
I
W
W
G
G
K
K
T
T
P
P
K
K
F
F
390
|
K
K
L
L
P
P
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
400
|
T
T
W
W
W
W
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
410
|
W
W
I
I
P
P
E
E
W
W
E
E
F
F
V
V
N
N
T
T
420
|
P
P
P
P
L
L
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
430
|
E
E
K
K
E
E
P
P
I
I
V
V
G
G
A
A
E
E
T
T
440
|
F
F
Y
Y
V
V
D
D
G
G
A
A
A
A
N
N
R
R
E
E
450
|
T
T
K
K
L
L
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
460
|
N
N
R
R
G
G
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
470
|
T
T
D
D
T
T
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
480
|
Q
Q
A
A
I
I
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
490
|
G
G
L
L
E
E
V
V
N
N
I
I
V
V
T
T
D
D
S
S
500
|
Q
Q
Y
Y
A
A
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
510
|
P
P
D
D
Q
Q
S
S
E
E
S
S
E
E
L
L
V
V
N
N
520
|
Q
Q
I
I
I
I
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
530
|
K
K
V
V
Y
Y
L
L
A
A
W
W
V
V
P
P
A
A
H
H
540
|
K
K
G
G
I
I
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
550
|
K
K
L
L
V
V
S
S
A
A
G
G
I
I
R
R
K
K
V
V
560
|
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M16MV+p.T69TN+p.V90I+p.L100I+p.K103N+p.D123E+p.I135V+p.G196E+p.P243S+p.V245E+p.E248DV+p.I293V+p.E297R
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.682
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2
TM score: 0.94789
Amino acid change:
M16V+T69N+V90I+L100I+K103N+D123E+I135V+G196E+P243S+V245E+E248DV+I293V+E297R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
S
S
P
P
I
I
E
E
T
T
V
V
P
P
10
|
V
V
K
K
L
L
K
K
P
P
G
G
M
V
D
D
G
G
P
P
20
|
K
K
V
V
K
K
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
30
|
K
K
I
I
K
K
A
A
L
L
V
V
E
E
I
I
C
C
T
T
40
|
E
E
M
M
E
E
K
K
E
E
G
G
K
K
I
I
S
S
K
K
50
|
I
I
G
G
P
P
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
60
|
V
V
F
F
A
A
I
I
K
K
K
K
K
K
D
D
S
S
T
N
70
|
K
K
W
W
R
R
K
K
L
L
V
V
D
D
F
F
R
R
E
E
80
|
L
L
N
N
K
K
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
90
|
V
I
Q
Q
L
L
G
G
I
I
P
P
H
H
P
P
A
A
G
G
100
|
L
I
K
K
K
K
K
N
K
K
S
S
V
V
T
T
V
V
L
L
110
|
D
D
V
V
G
G
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
120
|
L
L
D
D
E
E
D
E
F
F
R
R
K
K
Y
Y
T
T
A
A
130
|
F
F
T
T
I
I
P
P
S
S
I
V
N
N
N
N
E
E
T
T
140
|
P
P
G
G
I
I
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
150
|
P
P
Q
Q
G
G
W
W
K
K
G
G
S
S
P
P
A
A
I
I
160
|
F
F
Q
Q
S
S
S
S
M
M
T
T
K
K
I
I
L
L
E
E
170
|
P
P
F
F
R
R
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
180
|
I
I
Y
Y
Q
Q
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
190
|
G
G
S
S
D
D
L
L
E
E
I
I
G
E
Q
Q
H
H
R
R
200
|
T
T
K
K
I
I
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
210
|
L
L
R
R
W
W
G
G
L
L
T
T
T
T
P
P
D
D
K
K
220
|
K
K
H
H
Q
Q
K
K
E
E
P
P
P
P
F
F
L
L
W
W
230
|
M
M
G
G
Y
Y
E
E
L
L
H
H
P
P
D
D
K
K
W
W
240
|
T
T
V
V
Q
Q
P
S
I
I
V
E
L
L
P
P
E
D
K
K
250
|
D
D
S
S
W
W
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
260
|
L
L
V
V
G
G
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
270
|
I
I
Y
Y
P
P
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
280
|
C
C
K
K
L
L
L
L
R
R
G
G
T
T
K
K
A
A
L
L
290
|
T
T
E
E
V
V
I
V
P
P
L
L
T
T
E
R
E
E
A
A
300
|
E
E
L
L
E
E
L
L
A
A
E
E
N
N
R
R
E
E
I
I
310
|
L
L
K
K
E
E
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
320
|
D
D
P
P
S
S
K
K
D
D
L
L
I
I
A
A
E
E
I
I
330
|
Q
Q
K
K
Q
Q
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
340
|
Q
Q
I
I
Y
Y
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
350
|
K
K
T
T
G
G
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
360
|
A
A
H
H
T
T
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
370
|
E
E
A
A
V
V
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
380
|
I
I
V
V
I
I
W
W
G
G
K
K
T
T
P
P
K
K
F
F
390
|
K
K
L
L
P
P
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
400
|
T
T
W
W
W
W
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
410
|
W
W
I
I
P
P
E
E
W
W
E
E
F
F
V
V
N
N
T
T
420
|
P
P
P
P
L
L
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
430
|
E
E
K
K
E
E
P
P
I
I
V
V
G
G
A
A
E
E
T
T
440
|
F
F
Y
Y
V
V
D
D
G
G
A
A
A
A
N
N
R
R
E
E
450
|
T
T
K
K
L
L
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
460
|
N
N
R
R
G
G
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
470
|
T
T
D
D
T
T
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
480
|
Q
Q
A
A
I
I
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
490
|
G
G
L
L
E
E
V
V
N
N
I
I
V
V
T
T
D
D
S
S
500
|
Q
Q
Y
Y
A
A
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
510
|
P
P
D
D
Q
Q
S
S
E
E
S
S
E
E
L
L
V
V
N
N
520
|
Q
Q
I
I
I
I
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
530
|
K
K
V
V
Y
Y
L
L
A
A
W
W
V
V
P
P
A
A
H
H
540
|
K
K
G
G
I
I
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
550
|
K
K
L
L
V
V
S
S
A
A
G
G
I
I
R
R
K
K
V
V
560
|
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V60I+p.K64Y+p.D67N+p.K70R+p.V90VI+p.K101P+p.T139M+p.M184V+p.G190A+p.K219Q+p.E224D+p.L228H+p.V245E
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.895
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.15
TM score: 0.94128
Amino acid change:
V60I+K64Y+D67N+K70R+V90I+K101P+T139M+M184V+G190A+K219Q+E224D+L228H+V245E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
I
F
F
A
A
650
|
I
I
K
Y
K
K
K
K
D
N
S
S
T
T
K
R
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
I
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
P
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
M
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
A
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
R
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
Q
K
K
H
H
Q
Q
810
|
K
K
E
D
P
P
P
P
F
F
L
H
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
E
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.L74V+p.I142V+p.T165L+p.E169D+p.Y181I+p.M184V+p.R211K+p.T215Y
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.827
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.71
TM score: 0.96194
Amino acid change:
M41L+L74V+I142V+T165L+E169D+Y181I+M184V+R211K+T215Y
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
L
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
V
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
V
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
L
K
K
I
I
L
L
E
D
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
I
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
K
W
W
800
|
G
G
L
L
T
Y
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.E44D+p.D67N+p.T69D+p.K70KR+p.A98S+p.Y181I+p.L210W+p.R211K+p.T215Y+p.D218DE
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.394
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.65
TM score: 0.96426
Amino acid change:
M41L+E44D+D67N+T69D+K70R+A98S+Y181I+L210W+R211K+T215Y+D218E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
L
E
E
630
|
K
K
E
D
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
N
S
S
T
D
K
R
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
S
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
I
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
W
R
K
W
W
800
|
G
G
L
L
T
Y
T
T
P
P
D
E
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.K32KQ+p.M41L+p.E53ED+p.P59PS+p.L74V+p.I135T+p.Q145QR+p.Y181V+p.R211K+p.T215Y+p.K249R
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.709
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.7
TM score: 0.96273
Amino acid change:
K20R+K32Q+M41L+E53D+P59S+L74V+I135T+Q145R+Y181V+R211K+T215Y+K249R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
R
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
Q
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
L
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
D
N
N
P
P
Y
Y
N
N
T
T
P
S
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
V
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
T
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
R
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
V
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
K
W
W
800
|
G
G
L
L
T
Y
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
R
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20R, K32KQ, M41L, E53ED, P59PS, L74V, I135T, Q145QR, Y181V, R211K, T215Y, K249R.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [5]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V60VI+p.D67G+p.S68G+p.T69N+p.K70R+p.K101P+p.K102Q+p.K103S+p.I142IV+p.D177E+p.I178L+p.M184V+p.T200A+p.T215V+p.K219E+p.I293V+p.E297K
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.065
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.78
TM score: 0.95851
Amino acid change:
V60I+D67G+S68G+T69N+K70R+K101P+K102Q+K103S+I142V+D177E+I178L+M184V+T200A+T215V+K219E+I293V+E297K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
I
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
G
S
G
T
N
K
R
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
P
K
Q
690
|
K
S
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
V
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
E
I
L
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
A
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
R
W
W
800
|
G
G
L
L
T
V
T
T
P
P
D
D
K
E
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
V
P
P
L
L
T
T
E
K
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V60VI, D67G, S68G, T69N, K70R, K101P, K102Q, K103S, I142IV, D177E, I178L, M184V, T200A, T215V, K219E, I293V, E297K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D67N+p.T69N+p.K70R+p.V90I+p.K103N+p.V118I+p.I135M
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.147
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.27
TM score: 0.97825
Amino acid change:
D67N+T69N+K70R+V90I+K103N+V118I+I135M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
N
S
S
T
N
K
R
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
I
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
N
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
I
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
M
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
R
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D67N, T69N, K70R, V90I, K103N, V118I, I135M.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101E+p.K102Q+p.S162C+p.K277R+p.I293V
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description The k101E substitution conferred large reductions in susceptibility to NVP and DLV, while more modest reductions in susceptibility to EFV, ETR, or RPV were observed. In contrast, the E138k substitution did not confer large reductions in susceptibility to any of the NNRTIs and only small reductions in susceptibility to ETR and RPV. That is because that the k101E substitution compensates for the impaired viral replication capacity of HIV-1 containing M184I.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.E138K+p.S162C+p.K277R+p.I293V
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description The k101E substitution conferred large reductions in susceptibility to NVP and DLV, while more modest reductions in susceptibility to EFV, ETR, or RPV were observed. In contrast, the E138k substitution did not confer large reductions in susceptibility to any of the NNRTIs and only small reductions in susceptibility to ETR and RPV. That is because that the k101E substitution compensates for the impaired viral replication capacity of HIV-1 containing M184I.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101E+p.K102Q+p.E138K+p.S162C+p.M184I+p.K277R+p.I293V
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description The k101E substitution conferred large reductions in susceptibility to NVP and DLV, while more modest reductions in susceptibility to EFV, ETR, or RPV were observed. In contrast, the E138k substitution did not confer large reductions in susceptibility to any of the NNRTIs and only small reductions in susceptibility to ETR and RPV. That is because that the k101E substitution compensates for the impaired viral replication capacity of HIV-1 containing M184I.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.E138K+p.S162C+p.M184I+p.K277R+p.I293V
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description The k101E substitution conferred large reductions in susceptibility to NVP and DLV, while more modest reductions in susceptibility to EFV, ETR, or RPV were observed. In contrast, the E138k substitution did not confer large reductions in susceptibility to any of the NNRTIs and only small reductions in susceptibility to ETR and RPV. That is because that the k101E substitution compensates for the impaired viral replication capacity of HIV-1 containing M184I.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101E+p.K102Q+p.E138K+p.S162C+p.K277R+p.I293V
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description The k101E substitution conferred large reductions in susceptibility to NVP and DLV, while more modest reductions in susceptibility to EFV, ETR, or RPV were observed. In contrast, the E138k substitution did not confer large reductions in susceptibility to any of the NNRTIs and only small reductions in susceptibility to ETR and RPV. That is because that the k101E substitution compensates for the impaired viral replication capacity of HIV-1 containing M184I.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35I+p.K101KE+p.V106VI+p.D123E+p.I135T+p.K173T+p.Q174K+p.D177E+p.Y181I+p.M184V+p.G196E+p.T200K+p.Q207A+p.P243T+p.V245K+p.D256E+p.A272P+p.E291D+p.V292I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35E+p.T39A+p.E138K+p.D177E+p.V179VI+p.Y181I+p.M184V+p.E194EK+p.G196EK+p.Q207E+p.R211K+p.V245K+p.I257L+p.K277R+p.T286A+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20KR+p.A62AV+p.K65KN+p.V108VI+p.F171Y+p.D177E+p.I178IMV+p.M184MIV+p.T200A+p.Q207T+p.R211K+p.F227FC+p.L228LR+p.M230MI+p.L234LI+p.V245E+p.A272P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35IM+p.G45X+p.V90I+p.K101KE+p.K122E+p.D123N+p.I135L+p.S162C+p.Q174K+p.V179I+p.Y181I+p.M184V+p.G196E+p.A272P+p.A288T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.V90I+p.K122E+p.D123N+p.I135L+p.S162C+p.Q174K+p.V179I+p.Y181I+p.M184V+p.G196E+p.A272P+p.A288T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K11T+p.V35I+p.E40K+p.K65R+p.T69T_X+p.I135L+p.D177E+p.I178M+p.V179VI+p.Y181C+p.Y188H+p.V189VI+p.G196E+p.K219KE+p.E291D+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V8I+p.K20R+p.A98AG+p.K101KE+p.K122KE+p.D123X+p.E138EK+p.I178IM+p.Y181YC+p.M184I+p.R211K+p.H221HY+p.V245I+p.E248ED+p.A272P+p.K277KR+p.I293V+p.P294S+p.E297R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.D67G+p.A98S+p.K101E+p.K122E+p.D123G+p.Y181C+p.M184I+p.T200A+p.K219E+p.M230L+p.V245E+p.K277R+p.I293V+p.P294A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35L+p.T39A+p.K122E+p.D123DN+p.I135R+p.K173E+p.Q174QR+p.D177E+p.V179I+p.Y181C+p.M184V+p.G196E+p.T200I+p.I202IV+p.R211K+p.K249KR+p.A288S+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4S+p.D67DN+p.T69N+p.K70KR+p.V90I+p.L100LI+p.K122E+p.D123N+p.I135IL+p.S162C+p.D177E+p.V179I+p.M184I+p.Y188L+p.T200A+p.R211K+p.K219E+p.M230MIL+p.L234LI+p.A272P+p.K277R+p.T286A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4T+p.E6D+p.K20R+p.A33G+p.V60I+p.D67N+p.T69N+p.K70R+p.L74I+p.K101E+p.K103S+p.V118I+p.D123E+p.I135T+p.E138A+p.M184V+p.G190A+p.D192N+p.I195KR+p.G196E+p.E203K+p.R211A+p.F214L+p.K219Q+p.H221Y+p.I257L+p.A272P+p.K281R+p.E291D+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35M+p.T69D+p.K102Q+p.K103N+p.K122E+p.E138G+p.S162SC+p.I178L+p.Q207E+p.A272P+p.K277R+p.L283I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35L+p.M41L+p.K43E+p.D67N+p.T69N+p.K70R+p.K102Q+p.K103N+p.K122E+p.D123E+p.D177N+p.M184V+p.Y188L+p.G196E+p.I202V+p.R211T+p.T215F+p.D218E+p.K219Q+p.A272P+p.K277R+p.L283I+p.A288T+p.I293V+p.E297K+p.A304E
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35T+p.M41L+p.K43KN+p.V60I+p.K122E+p.K173KQ+p.D177EG+p.V179VI+p.Y188L+p.G196E+p.R211RK+p.T215D+p.V245E+p.I257L+p.K277R+p.I293V+p.E297R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35T+p.M41L+p.L80I+p.K122E+p.D177E+p.Y188L+p.H198E+p.T215D+p.V245VE+p.I257IL+p.K277R+p.A288AT+p.I293V+p.E297R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T39AE+p.M41L+p.K43KR+p.E44D+p.L74LI+p.A98AG+p.K102KR+p.K103N+p.K122E+p.D123S+p.I135T+p.I142V+p.M184V+p.Y188L+p.H208Y+p.L210W+p.R211K+p.T215Y+p.L228H+p.R284K+p.T286A+p.P294T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T69TN+p.K101P+p.K103N+p.I135V+p.I142V+p.Q145V+p.M184V+p.T200A+p.V245N+p.E248D+p.A272P+p.K275R+p.I293IV
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K22R+p.V35M+p.S162C+p.I178L+p.V179I+p.Y181C+p.M184V+p.Y188L+p.T200A+p.Q207E+p.V245E+p.A272P+p.K277R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.S3C+p.E28R+p.K32E+p.V35M+p.M41L+p.L74I+p.R83K+p.A98G+p.K101E+p.K103N+p.V108I+p.S162A+p.I167IV+p.E169D+p.D177E+p.I178L+p.M184V+p.G196E+p.T200A+p.E203D+p.Q207E+p.L210W+p.R211K+p.T215Y+p.L228H+p.L260V+p.A272P+p.K281R+p.T286A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E28K+p.K32E+p.T39K+p.M41L+p.K43E+p.E44A+p.V60I+p.D67N+p.V75M+p.R83K+p.K102KR+p.K103S+p.V118I+p.K122E+p.I135T+p.V179T+p.Y181V+p.M184V+p.T200A+p.E203V+p.Q207E+p.H208Y+p.L210W+p.R211K+p.T215Y+p.D218E+p.K219E+p.L228H+p.Q242H+p.V245E+p.D256E+p.A272P+p.T286TI+p.A288T+p.I293V+p.E297T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.I5IV+p.E6K+p.K20KR+p.E44ED+p.D67N+p.T69D+p.V90VI+p.K102Q+p.K103N+p.K104KR+p.V118I+p.K122E+p.I142IV+p.V179I+p.Y181C+p.Y188L+p.T200A+p.Q207N+p.R211K+p.F214L+p.H221Y+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35VI+p.T39TA+p.V90VI+p.L100I+p.Y115F+p.K122E+p.A158S+p.E169D+p.V179VI+p.M184V+p.Y188L+p.G196D+p.T200TA+p.Q207K+p.R211RK+p.T215F+p.K219E+p.L228H+p.V245E
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.K43Q+p.V60I+p.D67N+p.T69D+p.L74LV+p.V75VIM+p.L100I+p.K103N+p.K122KE+p.I135L+p.E138G+p.I142V+p.I178L+p.M184V+p.G196E+p.Q207E+p.T215Y+p.V245E+p.A272P+p.V276VI+p.K277KR+p.T286A+p.E291A+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4S+p.V35VA+p.S48E+p.K101KE+p.K103KN+p.E169A+p.K173E+p.I178IM+p.I180IL+p.T200TA+p.V245VI+p.A272P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35L+p.D67N+p.K70R+p.K101R+p.K103R+p.D177E+p.I178M+p.G190E+p.G196E+p.T200A+p.E204N+p.R211K+p.T215F+p.K219E+p.L228H+p.V245E+p.A272P+p.T286A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D67N+p.K70R+p.L74IV+p.L100I+p.K103N+p.D123E+p.I135T+p.K166R+p.G196E+p.T200A+p.I202V+p.T215I+p.K219E+p.L228LR+p.K277R+p.L283I+p.A288T+p.I293V+p.P294I+p.E297P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D67G+p.S68G+p.K70R+p.K101Q+p.K122E+p.V179I+p.Y181I+p.I195T+p.Q207E+p.R211K+p.F214L+p.K219Q+p.H221Y+p.L228H+p.V245E+p.A272P+p.K277R+p.T286A+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E6D+p.K103N+p.L109LS+p.D123E+p.I135T+p.S162A+p.M184IV+p.T200I+p.E204Q+p.Q207E+p.F214L+p.M230L+p.I244V+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K11KRT+p.V60VI+p.W88C+p.D121H+p.K122E+p.I135T+p.D177E+p.Y181C+p.R211K+p.H221Y+p.V245E+p.V254VI+p.A272P+p.A288G+p.E291D+p.I293IV+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E6D+p.K122E+p.E138A+p.I142T+p.D177E+p.I178M+p.I195L+p.I202V+p.R211K+p.V245I+p.A272P+p.L283I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.D67N+p.K70R+p.K122E+p.I135V+p.E138A+p.S162C+p.M184MV+p.G190E+p.T200A+p.F214M+p.T215F+p.K219Q+p.L228H+p.V245E
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.L74LV+p.Y115F+p.K122E+p.Y181C+p.M184V+p.R211K+p.F214L+p.H221Y+p.V241VM+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K11K*+p.K20R+p.K64R+p.D67G+p.K70R+p.K101P+p.K103N+p.D123E+p.R172K+p.M184V+p.Q207E+p.R211K+p.F214L+p.K219E+p.T253TS
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T39TA+p.D67N+p.K70R+p.V90I+p.K101E+p.S162N+p.M184V+p.G190A+p.E203D+p.R211K+p.F214FL+p.K219H+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.E44D+p.D67N+p.V118VI+p.I135T+p.S162C+p.R172K+p.Y188L+p.V189I+p.T200A+p.L210W+p.T215Y+p.D218E+p.K219R+p.V245E+p.A272P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K70KR+p.K122E+p.A158S+p.E169D+p.M184V+p.Y188L+p.G196D+p.Q207K+p.T215F+p.V245E
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V60I+p.T69N+p.K70R+p.I142V+p.V179D+p.Y188L+p.R211K+p.V245I+p.K277R+p.A288S+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M16MV+p.M41L+p.L74V+p.L100I+p.K103N+p.K122E+p.I135T+p.T139TA+p.K173KR+p.I178L+p.R211K+p.T215Y+p.A272P+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T7A+p.M41L+p.K43E+p.D67N+p.K101Q+p.V106I+p.D123E+p.I135L+p.Y181I+p.M184V+p.Q197L+p.L210W+p.R211K+p.T215Y+p.A272P+p.I293V+p.L303P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V60I+p.D67G+p.S68G+p.K70KR+p.L74V+p.I135V+p.E138A+p.K173E+p.I178M+p.G190E+p.R211A+p.K219N+p.V245E+p.E248D+p.D250E+p.A272P+p.T286A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35K+p.M41L+p.V60I+p.D67N+p.T69D+p.K70R+p.L74V+p.K101E+p.K104N+p.V118I+p.K122E+p.I135T+p.S162D+p.Y181C+p.M184V+p.G190S+p.F214L+p.T215F+p.K219Q+p.A272P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20KR+p.T165TI+p.T200AV+p.E204EG+p.F214FL+p.K277R+p.T286A+p.A288S
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20KR, T165TI, T200AV, E204EG, F214FL, K277R, T286A, A288S.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [7]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K122E+p.M184I+p.F214L+p.A272P+p.K277R+p.A376T+p.A400T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K122E, M184I, F214L, A272P, K277R, A376T, A400T.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [7]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K122E+p.F214L+p.A272P+p.K277R+p.A376T+p.A400T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K122E, F214L, A272P, K277R, A376T, A400T.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.R83K+p.K103N+p.I135T+p.E138G+p.K166KR+p.T200TA+p.H208HY+p.R211K+p.I244V+p.D250E+p.A272P+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35I, R83K, K103N, I135T, E138G, K166KR, T200TA, H208HY, R211K, I244V, D250E, A272P, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35IM+p.T39TA+p.R83K+p.K102KQ+p.K103N+p.D123E+p.S162C+p.D177E+p.I178R+p.V179F+p.R211RK+p.V245EQ+p.D250E+p.K277R+p.T286A+p.I293V+p.M357AS+p.E370ED+p.T377TMI
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35IM, T39TA, R83K, K102KQ, K103N, D123E, S162C, D177E, I178R, V179F, R211RK, V245EQ, D250E, K277R, T286A, I293V, M357AS, E370ED, T377TMI.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20KR+p.K22R+p.V106I+p.I178L+p.R211K+p.F214FL+p.D250E+p.S251SN+p.K277R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20KR, K22R, V106I, I178L, R211K, F214FL, D250E, S251SN, K277R.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20KR+p.V35I+p.K101H+p.I135V+p.S162C+p.D177E+p.I178IV+p.G190A+p.T200E+p.E203ED+p.R211K+p.I244IV+p.V245M+p.A272P+p.T286A+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20KR, V35I, K101H, I135V, S162C, D177E, I178IV, G190A, T200E, E203ED, R211K, I244IV, V245M, A272P, T286A, I293V, E297A.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35M+p.T69D+p.K102Q+p.K122KE+p.E138EAG+p.S162C+p.I178L+p.M184MV+p.Q207E+p.A272P+p.K277R+p.L283I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20R, V35M, T69D, K102Q, K122KE, E138EAG, S162C, I178L, M184MV, Q207E, A272P, K277R, L283I, I293V, E297A.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [7]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K122E+p.E138K+p.M184V+p.F214L+p.A272P+p.K277R+p.A376T+p.A400T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K122E, E138K, M184V, F214L, A272P, K277R, A376T, A400T.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D67G+p.K70E+p.V90I+p.K122E+p.I135IT+p.S162F+p.I178IM+p.Y181C+p.T200E+p.R211HQ+p.V245E+p.A272P+p.K277R+p.T286A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D67G, K70E, V90I, K122E, I135IT, S162F, I178IM, Y181C, T200E, R211HQ, V245E, A272P, K277R, T286A, E297K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D67G+p.K70E+p.V90I+p.K102Q+p.I135T+p.S162F+p.I178IM+p.Y181C+p.T200E+p.R211QH+p.V245E+p.K277R+p.T286A+p.I293V+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D67G, K70E, V90I, K102Q, I135T, S162F, I178IM, Y181C, T200E, R211QH, V245E, K277R, T286A, I293V, E297K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [7]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K122E+p.E138K+p.F214L+p.A272P+p.K277R+p.A376T+p.A400T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K122E, E138K, F214L, A272P, K277R, A376T, A400T.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [7]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K122E+p.E138K+p.M184I+p.F214L+p.A272P+p.K277R+p.A376T+p.A400T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K122E, E138K, M184I, F214L, A272P, K277R, A376T, A400T.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.A62V+p.D67N+p.T69D+p.V75I+p.R83K+p.K103N+p.V108I+p.F116Y+p.D123E+p.Q151M+p.K166R+p.D177E+p.I202V+p.L210W+p.T215Y+p.M230L+p.A272P+p.I293V+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M41L, A62V, D67N, T69D, V75I, R83K, K103N, V108I, F116Y, D123E, Q151M, K166R, D177E, I202V, L210W, T215Y, M230L, A272P, I293V, E297K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D123E+p.E138EK+p.S162C+p.I178L+p.Q207E+p.R211K+p.A272P+p.K277R+p.T286A+p.A288T+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D123E, E138EK, S162C, I178L, Q207E, R211K, A272P, K277R, T286A, A288T, E297K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35M+p.K70E+p.K102Q+p.K103N+p.D123E+p.S162C+p.K173E+p.Q174R+p.I178L+p.M184V+p.T200A+p.R211K+p.L228HR+p.M230L+p.L234I+p.V245KQ+p.K277R+p.L283I+p.V292I+p.I293V+p.Q334QR+p.G335X+p.T369TA+p.V381VI
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35M, K70E, K102Q, K103N, D123E, S162C, K173E, Q174R, I178L, M184V, T200A, R211K, L228HR, M230L, L234I, V245KQ, K277R, L283I, V292I, I293V, Q334QR, G335X, T369TA, V381VI.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.A98G+p.K101E+p.K122E+p.I135T+p.E138K+p.S162Y+p.Y181C+p.T200A+p.L210F+p.T215D+p.P243T+p.V245E+p.D250E+p.A272P+p.I274V+p.Q278H+p.K281R+p.T286A+p.A288S+p.K311R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M41L, A98G, K101E, K122E, I135T, E138K, S162Y, Y181C, T200A, L210F, T215D, P243T, V245E, D250E, A272P, I274V, Q278H, K281R, T286A, A288S, K311R.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.A98S+p.K101P+p.K102Q+p.K103N+p.D123E+p.K166R+p.D177E+p.D192N+p.R211K+p.T215Y+p.V245K+p.K277R+p.R284K+p.T286A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M41L, A98S, K101P, K102Q, K103N, D123E, K166R, D177E, D192N, R211K, T215Y, V245K, K277R, R284K, T286A, E297K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.K64KR+p.L74V+p.K103N+p.V108I+p.Y181C+p.M184V+p.T200A+p.R211K+p.H221Y+p.L228H+p.V245L+p.A272P+p.K277R+p.T286A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20R, K64KR, L74V, K103N, V108I, Y181C, M184V, T200A, R211K, H221Y, L228H, V245L, A272P, K277R, T286A.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.K122E+p.E138G+p.D177E+p.I178L+p.L210W+p.R211K+p.T215Y+p.H221Y+p.F227L+p.M230L+p.V245M+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M41L, K122E, E138G, D177E, I178L, L210W, R211K, T215Y, H221Y, F227L, M230L, V245M, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35L+p.T39A+p.K101P+p.K103KR+p.K122E+p.I135R+p.D177E+p.I178M+p.T200TA+p.R211K+p.A272P+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20R, V35L, T39A, K101P, K103KR, K122E, I135R, D177E, I178M, T200TA, R211K, A272P, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.M41L+p.D67G+p.L74I+p.L100I+p.K103R+p.K122E+p.V179D+p.M184V+p.I202V+p.R211K+p.T215Y+p.M230L+p.T240K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35I, M41L, D67G, L74I, L100I, K103R, K122E, V179D, M184V, I202V, R211K, T215Y, M230L, T240K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35I+p.K65KR+p.L74LV+p.K103N+p.K122E+p.Y181C+p.T200A+p.R211K+p.F227C+p.M230L+p.V245Q+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K20R, V35I, K65KR, L74LV, K103N, K122E, Y181C, T200A, R211K, F227C, M230L, V245Q, I293V, E297A.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.K43Q+p.A62AV+p.T69S_ST+p.K101P+p.K103N+p.V118I+p.K122E+p.S162D+p.K166R+p.D177N+p.V179I+p.M184V+p.T200A+p.Q207E+p.L210F+p.R211K+p.T215Y+p.V245E+p.A272P+p.K277R+p.E291D+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M41L, K43Q, A62AV, T69S_ST, K101P, K103N, V118I, K122E, S162D, K166R, D177N, V179I, M184V, T200A, Q207E, L210F, R211K, T215Y, V245E, A272P, K277R, E291D, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T39TP+p.D67N+p.K70R+p.V90I+p.K101P+p.K102R+p.K103N+p.K122E+p.I135V+p.Q151M+p.G196E+p.Q207K+p.R211A+p.K219Q+p.L228LH+p.E248D+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T39TP, D67N, K70R, V90I, K101P, K102R, K103N, K122E, I135V, Q151M, G196E, Q207K, R211A, K219Q, L228LH, E248D, I293V, E297A.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.L100I+p.K102Q+p.K103R+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L100I, K102Q, K103R, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.K103R+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, K103R, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.K43N+p.D67G+p.T69N+p.K70R+p.L74I+p.K103N+p.I142V+p.Y181C+p.M184V+p.G196E+p.I202V+p.T215F+p.K219Q+p.V245K+p.K277R+p.A288S+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M41L, K43N, D67G, T69N, K70R, L74I, K103N, I142V, Y181C, M184V, G196E, I202V, T215F, K219Q, V245K, K277R, A288S, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.K103S+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, K103S, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35R+p.M41L+p.K49R+p.V60I+p.K64H+p.D67N+p.T69N+p.K70R+p.V108I+p.K122Q+p.I135T+p.S162D+p.D177E+p.Y181C+p.M184V+p.V189I+p.T200A+p.T215F+p.D218E+p.K219Q+p.L228R+p.V245E
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35R, M41L, K49R, V60I, K64H, D67N, T69N, K70R, V108I, K122Q, I135T, S162D, D177E, Y181C, M184V, V189I, T200A, T215F, D218E, K219Q, L228R, V245E.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.E138A+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, E138A, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.S162C+p.Y181C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, S162C, Y181C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.E138G+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, E138G, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K64H+p.D67N+p.T69N+p.K70R+p.V90I+p.K103N+p.V118I+p.I135M+p.T215E+p.K219Q+p.A272P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K64H, D67N, T69N, K70R, V90I, K103N, V118I, I135M, T215E, K219Q, A272P.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101Q+p.K102Q+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K101Q, K102Q, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.E138R+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, E138R, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101E+p.K102Q+p.S162C+p.M184V+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K101E, K102Q, S162C, M184V, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35T+p.K43R+p.K64Y+p.D67N+p.K70R+p.L74I+p.K103S+p.V106A+p.D123E+p.D177E+p.M184V+p.G196E+p.T200A+p.R211S+p.T215F+p.K219Q+p.L228H+p.Q242H+p.K277R+p.R284K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35T, K43R, K64Y, D67N, K70R, L74I, K103S, V106A, D123E, D177E, M184V, G196E, T200A, R211S, T215F, K219Q, L228H, Q242H, K277R, R284K.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101E+p.K102Q+p.S162C+p.M184I+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K101E, K102Q, S162C, M184I, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101E+p.K102Q+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K101E, K102Q, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35R+p.M41L+p.K49R+p.V60I+p.D67N+p.T69N+p.K70R+p.V108I+p.K122Q+p.I135T+p.S162D+p.D177E+p.Y181C+p.M184V+p.V189I+p.T200A+p.T215F+p.D218E+p.K219Q+p.L228R+p.V245E+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V35R, M41L, K49R, V60I, D67N, T69N, K70R, V108I, K122Q, I135T, S162D, D177E, Y181C, M184V, V189I, T200A, T215F, D218E, K219Q, L228R, V245E, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.K103R+p.S162C+p.V179D+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, K103R, S162C, V179D, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.E138Q+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, E138Q, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [11]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.Y188L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Y188L.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.L100I+p.K102Q+p.K103R+p.S162C+p.V179D+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L100I, K102Q, K103R, S162C, V179D, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K102Q+p.S162C+p.Y181I+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K102Q, S162C, Y181I, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K101P+p.K102Q+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K101P, K102Q, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.L100I+p.K102Q+p.K103N+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L100I, K102Q, K103N, S162C, K277R, I293V.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.L100I+p.K102Q+p.K103S+p.S162C+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance
PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L100I, K102Q, K103S, S162C, K277R, I293V.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.S48T+p.R211N+p.V245N+p.L283I+p.V292I+p.I293V
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.034
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.28
TM score: 0.97786
Amino acid change:
S48T+R211N+V245N+L283I+V292I+I293V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
T
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
N
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
N
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
I
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
I
880
|
I
V
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K11KR+p.V35I+p.R83K+p.T200TA+p.Q207A+p.R211K+p.I293V
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.008
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.34
TM score: 0.97606
Amino acid change:
K11R+V35I+R83K+T200A+Q207A+R211K+I293V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
R
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
I
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
K
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
A
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
A
H
H
L
L
L
L
R
K
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
V
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.R83K+p.D177E+p.G196E+p.H208HY+p.L210LF+p.R211K+p.E291D+p.E297K
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.859
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.74
TM score: 0.96058
Amino acid change:
V35I+R83K+D177E+G196E+H208Y+L210F+R211K+E291D+E297K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
I
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
K
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
E
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
E
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
Y
L
L
L
F
R
K
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
D
V
V
880
|
I
I
P
P
L
L
T
T
E
K
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.R83K+p.S162A+p.I178IM+p.Q207E+p.I293V+p.E297A+p.L301M
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.996
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.3
TM score: 0.97747
Amino acid change:
V35I+R83K+S162A+I178M+Q207E+I293V+E297A+L301M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
I
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
K
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
A
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
M
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
E
H
H
L
L
L
L
R
R
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
V
P
P
L
L
T
T
E
A
E
E
A
A
E
E
L
M
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E6D+p.M41L+p.E44D+p.K49R+p.V60I+p.D67N+p.K70R+p.K103N+p.V108VI+p.D123E+p.I135T+p.M184V+p.T200I+p.I202V+p.T215V+p.K219E+p.P225PH+p.L228H+p.V245T+p.E248K+p.K249KR+p.I293V+p.E297A
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.004
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.95
TM score: 0.94902
Amino acid change:
E6D+M41L+E44D+K49R+V60I+D67N+K70R+K103N+V108I+D123E+I135T+M184V+T200I+I202V+T215V+K219E+P225H+L228H+V245T+E248K+K249R+I293V+E297A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
D
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
L
E
E
630
|
K
K
E
D
G
G
K
K
I
I
S
S
K
R
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
I
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
N
S
S
T
T
K
R
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
N
K
K
S
S
V
V
T
T
V
I
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
E
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
T
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
I
K
K
I
V
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
R
W
W
800
|
G
G
L
L
T
V
T
T
P
P
D
D
K
E
K
K
H
H
Q
Q
810
|
K
K
E
E
P
H
P
P
F
F
L
H
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
T
L
L
P
P
E
K
K
R
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
V
P
P
L
L
T
T
E
A
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V90I+p.D123E+p.I202V+p.E204Q+p.Q207D+p.R211K+p.V245T+p.I293V+p.E297A
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.863
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.31
TM score: 0.97688
Amino acid change:
V90I+D123E+I202V+E204Q+Q207D+R211K+V245T+I293V+E297A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
I
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
E
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
M
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
V
790
|
E
E
E
Q
L
L
R
R
Q
D
H
H
L
L
L
L
R
K
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
T
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
V
P
P
L
L
T
T
E
A
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4PH+p.K20R+p.T39A+p.L74LI+p.R83K+p.V106VI+p.V179VI+p.M184V+p.E224D+p.V245E+p.T286A+p.P294PS+p.E297A
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.637
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.96475
Amino acid change:
P4H+K20R+T39A+L74I+R83K+V106I+V179I+M184V+E224D+V245E+T286A+P294S+E297A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
H
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
R
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
A
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
S
T
T
K
K
W
W
R
R
660
|
K
K
L
I
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
K
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
I
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
I
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
I
I
I
Y
Y
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
L
R
R
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
D
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
E
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
A
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
S
L
L
T
T
E
A
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.D67N+p.K70R+p.I135T+p.S162C+p.Q174QE+p.Y181C+p.M184V+p.Q207KR+p.R211Q+p.K219Q+p.H221Y+p.I293V
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 86.816
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.87
TM score: 0.95354
Amino acid change:
D67N+K70R+I135T+S162C+Q174E+Y181C+M184V+Q207KR+R211Q+K219Q+H221Y+I293V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
E
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
N
S
S
T
T
K
R
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
A
G
G
L
L
K
K
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
D
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
T
N
N
N
N
E
E
T
T
P
P
G
G
I
I
730
|
R
R
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
C
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
E
N
N
P
P
D
D
I
I
V
V
I
I
Y
C
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
K
H
H
L
L
L
L
R
Q
W
W
800
|
G
G
L
L
T
T
T
T
P
P
D
D
K
Q
K
K
H
Y
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
T
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
V
P
P
L
L
T
T
E
E
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E28K+p.S68G+p.A98S+p.K101E+p.D123E+p.I135V+p.I142IT+p.R143RG+p.M184V+p.L210LW+p.R211K+p.T215Y+p.T286TA+p.E297A
Wild Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 3QIP
Mutant Type Structure Method: AlphaFold  Average pLDDT: 87.235
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.83
TM score: 0.95514
Amino acid change:
E28K+S68G+A98S+K101E+D123E+I135V+I142T+R143G+M184V+L210W+R211K+T215Y+T286A+E297A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
P
P
I
I
590
|
S
S
P
P
I
I
E
E
T
T
V
V
P
P
V
V
K
K
L
L
600
|
K
K
P
P
G
G
M
M
D
D
G
G
P
P
K
K
V
V
K
K
610
|
Q
Q
W
W
P
P
L
L
T
T
E
K
E
E
K
K
I
I
K
K
620
|
A
A
L
L
V
V
E
E
I
I
C
C
T
T
E
E
M
M
E
E
630
|
K
K
E
E
G
G
K
K
I
I
S
S
K
K
I
I
G
G
P
P
640
|
E
E
N
N
P
P
Y
Y
N
N
T
T
P
P
V
V
F
F
A
A
650
|
I
I
K
K
K
K
K
K
D
D
S
G
T
T
K
K
W
W
R
R
660
|
K
K
L
L
V
V
D
D
F
F
R
R
E
E
L
L
N
N
K
K
670
|
R
R
T
T
Q
Q
D
D
F
F
W
W
E
E
V
V
Q
Q
L
L
680
|
G
G
I
I
P
P
H
H
P
P
A
S
G
G
L
L
K
E
K
K
690
|
K
K
K
K
S
S
V
V
T
T
V
V
L
L
D
D
V
V
G
G
700
|
D
D
A
A
Y
Y
F
F
S
S
V
V
P
P
L
L
D
D
E
E
710
|
D
E
F
F
R
R
K
K
Y
Y
T
T
A
A
F
F
T
T
I
I
720
|
P
P
S
S
I
V
N
N
N
N
E
E
T
T
P
P
G
G
I
T
730
|
R
G
Y
Y
Q
Q
Y
Y
N
N
V
V
L
L
P
P
Q
Q
G
G
740
|
W
W
K
K
G
G
S
S
P
P
A
A
I
I
F
F
Q
Q
S
S
750
|
S
S
M
M
T
T
K
K
I
I
L
L
E
E
P
P
F
F
R
R
760
|
K
K
Q
Q
N
N
P
P
D
D
I
I
V
V
I
I
Y
Y
Q
Q
770
|
Y
Y
M
V
D
D
D
D
L
L
Y
Y
V
V
G
G
S
S
D
D
780
|
L
L
E
E
I
I
G
G
Q
Q
H
H
R
R
T
T
K
K
I
I
790
|
E
E
E
E
L
L
R
R
Q
Q
H
H
L
L
L
W
R
K
W
W
800
|
G
G
L
L
T
Y
T
T
P
P
D
D
K
K
K
K
H
H
Q
Q
810
|
K
K
E
E
P
P
P
P
F
F
L
L
W
W
M
M
G
G
Y
Y
820
|
E
E
L
L
H
H
P
P
D
D
K
K
W
W
T
T
V
V
Q
Q
830
|
P
P
I
I
V
V
L
L
P
P
E
E
K
K
D
D
S
S
W
W
840
|
T
T
V
V
N
N
D
D
I
I
Q
Q
K
K
L
L
V
V
G
G
850
|
K
K
L
L
N
N
W
W
A
A
S
S
Q
Q
I
I
Y
Y
P
P
860
|
G
G
I
I
K
K
V
V
R
R
Q
Q
L
L
C
C
K
K
L
L
870
|
L
L
R
R
G
G
T
A
K
K
A
A
L
L
T
T
E
E
V
V
880
|
I
I
P
P
L
L
T
T
E
A
E
E
A
A
E
E
L
L
E
E
890
|
L
L
A
A
E
E
N
N
R
R
E
E
I
I
L
L
K
K
E
E
900
|
P
P
V
V
H
H
G
G
V
V
Y
Y
Y
Y
D
D
P
P
S
S
910
|
K
K
D
D
L
L
I
I
A
A
E
E
I
I
Q
Q
K
K
Q
Q
920
|
G
G
Q
Q
G
G
Q
Q
W
W
T
T
Y
Y
Q
Q
I
I
Y
Y
930
|
Q
Q
E
E
P
P
F
F
K
K
N
N
L
L
K
K
T
T
G
G
940
|
K
K
Y
Y
A
A
R
R
M
M
R
R
G
G
A
A
H
H
T
T
950
|
N
N
D
D
V
V
K
K
Q
Q
L
L
T
T
E
E
A
A
V
V
960
|
Q
Q
K
K
I
I
T
T
T
T
E
E
S
S
I
I
V
V
I
I
970
|
W
W
G
G
K
K
T
T
P
P
K
K
F
F
K
K
L
L
P
P
980
|
I
I
Q
Q
K
K
E
E
T
T
W
W
E
E
T
T
W
W
W
W
990
|
T
T
E
E
Y
Y
W
W
Q
Q
A
A
T
T
W
W
I
I
P
P
1000
|
E
E
W
W
E
E
F
F
V
V
N
N
T
T
P
P
P
P
L
L
1010
|
V
V
K
K
L
L
W
W
Y
Y
Q
Q
L
L
E
E
K
K
E
E
1020
|
P
P
I
I
V
V
G
G
A
A
E
E
T
T
F
F
Y
Y
V
V
1030
|
D
D
G
G
A
A
A
A
N
N
R
R
E
E
T
T
K
K
L
L
1040
|
G
G
K
K
A
A
G
G
Y
Y
V
V
T
T
N
N
R
R
G
G
1050
|
R
R
Q
Q
K
K
V
V
V
V
T
T
L
L
T
T
D
D
T
T
1060
|
T
T
N
N
Q
Q
K
K
T
T
E
E
L
L
Q
Q
A
A
I
I
1070
|
Y
Y
L
L
A
A
L
L
Q
Q
D
D
S
S
G
G
L
L
E
E
1080
|
V
V
N
N
I
I
V
V
T
T
D
D
S
S
Q
Q
Y
Y
A
A
1090
|
L
L
G
G
I
I
I
I
Q
Q
A
A
Q
Q
P
P
D
D
Q
Q
1100
|
S
S
E
E
S
S
E
E
L
L
V
V
N
N
Q
Q
I
I
I
I
1110
|
E
E
Q
Q
L
L
I
I
K
K
K
K
E
E
K
K
V
V
Y
Y
1120
|
L
L
A
A
W
W
V
V
P
P
A
A
H
H
K
K
G
G
I
I
1130
|
G
G
G
G
N
N
E
E
Q
Q
V
V
D
D
K
K
L
L
V
V
1140
|
S
S
A
A
G
G
I
I
R
R
K
K
V
V
L
L
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V8VI+p.K20KR+p.V35I+p.D123E+p.I135T+p.K173T+p.Q174K+p.D177E+p.V179VD+p.G196E+p.T200K+p.Q207A+p.P243T+p.V245K+p.D256E+p.A272AP+p.T286TA+p.E291D+p.V292I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T39S+p.S48T+p.V60I+p.S68G+p.K102Q+p.K122KE+p.D123X+p.A158S+p.I178L+p.V179DE+p.I195IL+p.T200TA+p.R211K+p.I244V+p.V245E+p.A272P+p.K277KR+p.R284K+p.A288S+p.V292I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35E+p.T39A+p.D177E+p.G196E+p.Q207E+p.R211K+p.V245K+p.I257L+p.K277R+p.T286A+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35T+p.E40ED+p.V60I+p.K122KE+p.I135V+p.S162A+p.K173T+p.Q174EK+p.P176PS+p.D177E+p.I178M+p.T200A+p.E204EK+p.Q207E+p.R211K+p.V245Q+p.A272P+p.K277R+p.K281R+p.T286A+p.I293V+p.P294T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35M+p.K49KR+p.V60I+p.R83K+p.K122E+p.I135T+p.S162H+p.E248D+p.A272P+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.A98S+p.K122E+p.A158AS+p.I159IV+p.S162SA+p.D177E+p.G196E+p.R211S+p.A272S+p.T286A+p.P294T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.F171Y+p.D177E+p.I178IMV+p.T200A+p.Q207T+p.R211K+p.V245E+p.A272P+p.K277KR
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.K122E+p.D123N+p.I135L+p.S162C+p.K173N+p.Q174K+p.V179I+p.G196E+p.A272P+p.A288T
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E6ED+p.V8VI+p.V35I+p.D86DE+p.K122P+p.D123E+p.I135L+p.T139I+p.D177E+p.Q207QK+p.R211RK+p.A272P+p.T286A+p.A288AG+p.I293IV
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20KR+p.V60I+p.S68G+p.I178ILM+p.G196E+p.T200TA+p.E248D+p.A272P+p.G273R+p.K275R+p.K281KR+p.V292I+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V8I+p.K20R+p.T69TA+p.K122KE+p.D123X+p.I178IM+p.R211K+p.V245VI+p.E248ED+p.A272P+p.K277R+p.I293V+p.P294S+p.E297R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.T39TA+p.T69TA+p.K82KR+p.R83RK+p.S162SN+p.P170PL+p.K173Q+p.I178M+p.T200A+p.Q207E+p.R211K+p.P225PL+p.L228LF+p.A272P+p.K277KR+p.L282LF+p.I293V+p.T296S+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.L80LF+p.A98S+p.K122E+p.T128TA+p.K166KR+p.I178IL+p.R211K+p.V245E+p.K277R+p.I293V+p.P294A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [3]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35L+p.T39A+p.R83RK+p.K122E+p.I135R+p.K173E+p.D177E+p.V179I+p.G196E+p.T200I+p.I202V+p.R211K+p.V245VE+p.A288S+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
GeneSeq assay; PhenoSense GT assay
Experiment for
Drug Resistance
Viral load assay
Mechanism Description Amino acid changes in IN may contribute to drug resistance or sensitivity.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E6D+p.V106I+p.V118I+p.I135V+p.T165I+p.T200A+p.F214L+p.V245R+p.D250E+p.A272P
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.M41L+p.K43Q+p.E44D+p.V60I+p.D67N+p.G93GR+p.K101H+p.V118I+p.K122P+p.D123E+p.I135T+p.I142V+p.D177E+p.I178IM+p.M184V+p.G190A+p.G196E+p.E203K+p.Q207E+p.L210W+p.R211K+p.T215Y+p.A272P+p.K277R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K64KR+p.K102KR+p.D123E+p.K173X+p.P176PAT+p.D177DE+p.I178L+p.M184MV+p.Q197QEK+p.Q207E+p.R211K+p.V245VI+p.E248D+p.A272P+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.S48T+p.K101KR+p.K103N+p.V106VI+p.T139TA+p.P157PS+p.T200I+p.E203D+p.Q207E+p.R211RK+p.D250E+p.A272P+p.K275R+p.K277R+p.T286TA+p.I293IV
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4T+p.E6K+p.K20R+p.T39TK+p.M41L+p.K43E+p.E44AD+p.D67N+p.L74I+p.K101E+p.V118I+p.K122E+p.S162A+p.V179F+p.Y181C+p.M184V+p.G190A+p.I195K+p.L210W+p.R211K+p.T215Y+p.K219N+p.V245K+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.K122E+p.R211K+p.V245M+p.G262GE+p.A272P+p.V292VI+p.I293IV+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4S+p.E6D+p.K122E+p.D123N+p.I142V+p.S162C+p.D177E+p.I178L+p.R211K+p.A272P+p.I293V+p.E297R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.E6K+p.V35I+p.T39TI+p.K102KQ+p.V106VI+p.K122E+p.I135IMV+p.I142M+p.S162C+p.R211K+p.K277R+p.A288S+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.I50IV+p.R83K+p.K166KR+p.K173X+p.Q174K+p.D177DE+p.I178L+p.V189VI+p.Q197QK+p.H198GE+p.Q207E+p.R211K+p.V245EQ+p.D250E+p.A272P+p.K277R
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35T+p.T39TR+p.K122KE+p.D177E+p.K281R+p.T286A+p.I293IV+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.R83K+p.K101KE+p.K122E+p.D123DE+p.S162A+p.Q174G+p.G196E+p.T200A+p.Q207E+p.V245E+p.A272P+p.K277R+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35T+p.T39E+p.K46T+p.E53D+p.V60I+p.K64KR+p.K101Q+p.K104KR+p.K122E+p.D123S+p.I135K+p.K166R+p.K173A+p.D177E+p.T200A+p.Q207E+p.R211K+p.V245E+p.D250E+p.V254I+p.A272P+p.K277R+p.T286A+p.E291D+p.V292I+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.I135V+p.P176S+p.D177E+p.A272P+p.G285A+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K13KR+p.K122E+p.I135T+p.S162C+p.M184V+p.G196E+p.K277R+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V35M+p.T69D+p.K102Q+p.K122KE+p.E138EAG+p.S162C+p.I178L+p.M184MV+p.Q207E+p.A272P+p.K277R+p.L283I+p.I293V+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20R+p.V60I+p.V90I+p.K101Q+p.K103N+p.V108I+p.I135V+p.I142V+p.D177E+p.M184I+p.T200I+p.R211K+p.T215D+p.A272P+p.V276I+p.L283I+p.I293V+p.E302EG
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.P4S+p.K122KE+p.D123E+p.E169D+p.I178L+p.T200A+p.I202IV+p.R211K+p.L246LP+p.E248D+p.A272P+p.T286TA+p.V292VI+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35VIL+p.K103N+p.K122E+p.K173Q+p.I178M+p.M184MV+p.T200TA+p.V245M+p.E248D+p.D250DE+p.T286A+p.A288S
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V60I+p.I135V+p.D177E+p.R211K+p.I244V+p.V245I+p.D250E+p.A272P+p.K277KR+p.E297V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.V35I+p.R83RK+p.T165TI+p.F171Y+p.T200A+p.I202V+p.V245M+p.A272P+p.K277R+p.T286A+p.P294Q+p.E297A
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.I135V+p.Y181C+p.M184V+p.G196E+p.T200A+p.Q207E+p.R211K+p.T215Y+p.V245K+p.K277R+p.E291D+p.E297K
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [2]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration Missense mutation
p.K20KR+p.T27TS+p.V60I+p.R83K+p.K122KE+p.Q174L+p.I178IL+p.T200X+p.R211RK+p.V245E+p.L283LI+p.T286TA+p.I293V
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Site-directed mutagenesis; Sanger sequencing assay
Experiment for
Drug Resistance
PhenoSense assay
Mechanism Description Sixteen mutations at eight positions had a mean regression coefficient >=1.0 log10 (a contribution to decreased susceptibility of 10-fold or greater) for nevirapine, efavirenz, etravirine and/or rilpivirine: L100I, k101P, k103N/S, V106A/M, Y181C/I/V, Y188C/L, G190A/E/Q/S and F227C. With the exception of L100I and F227C, each mutation had a mean regression coefficient >=1.0 log10 for nevirapine. With the exception of k103S, V106A, Y181C/I/V and F227C, each had a mean regression coefficient >=1.0 log10 for efavirenz. Five mutations, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >=1.0 log10 for etravirine. Six mutations, L100I, k101P, Y181I/V, G190E and F227C, had a mean regression coefficient >= 1.0 log10 for rilpivirine.
References
Ref 1 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2013 Nov;57(11):5649-57. doi: 10.1128/AAC.01536-13. Epub 2013 Sep 3.
Ref 2 Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother. 2014 Jan;69(1):12-20. doi: 10.1093/jac/dkt316. Epub 2013 Aug 9.
Ref 3 Characterization of HIV-1 drug resistance development through week 48 in antiretroviral naive subjects on rilpivirine/emtricitabine/tenofovir DF or efavirenz/emtricitabine/tenofovir DF in the STaR study (GS-US-264-0110). J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):318-26. doi: 10.1097/QAI.0000000000000017.
Ref 4 Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibilityAntimicrob Agents Chemother. 2012 May;56(5):2305-13. doi: 10.1128/AAC.05487-11. Epub 2012 Feb 13.
Ref 5 Genotypic predictors of human immunodeficiency virus type 1 drug resistanceProc Natl Acad Sci U S A. 2006 Nov 14;103(46):17355-60. doi: 10.1073/pnas.0607274103. Epub 2006 Oct 25.
Ref 6 Phenotypic evidence for NRTI resistance in HIV-1 isolates with the RT mutation K64H.
Ref 7 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitnessJ Acquir Immune Defic Syndr. 2012 Jan 1;59(1):47-54. doi: 10.1097/QAI.0b013e31823aca74.
Ref 8 Panel of prototypical recombinant infectious molecular clones resistant to nevirapine, efavirenz, etravirine, and rilpivirineAntimicrob Agents Chemother. 2012 Aug;56(8):4522-4. doi: 10.1128/AAC.00648-12. Epub 2012 Jun 4.
Ref 9 Combinations of HIV-1 reverse transcriptase mutations L100I+K103N/S and L100I+K103R+V179D reduce susceptibility to rilpivirine.
Ref 10 Comparison of the Antivirogram and PhenoSense assays to determine phenotypic susceptibility to rilpivirine in patient samples from the Phase III ECHO and THRIVE trials.
Ref 11 Mutation Y188L of HIV-1 reverse transcriptase is strongly associated with reduced susceptibility to rilpivirine

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