Interpretation du genotype

September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: NUCLEOSIDE AND NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
• T215Y/F
• T215A/C/D/E/G/H/I/L/N/S/V [1, 2, 3, 4]
• At least 3 mutations among: M41L, D67N, K70R, L210W,
T215A/C/D/E/G/H/I/L/N/S/V, K219Q/E [1, 2, 3, 4]
• Q151M
• Insertion at codon 69
• M184V/I
K65R [11, 12, 16]
Insertion at codon 69
• Q151M
• At least a score of + 2 among: M41L + T69D + 215Y/F + K219Q/E – K70R
• K65R [11, 12]
– M184 V/I [5, 14, 15, 17, 18]
• L74V/I [19]
• Q151M
• Insertion at codon 69
• V75A/M/S/T
• T215A/C/D/E/G/H/I/L/N/S/V [4, 7]
• T215Y/F [6]
• At least 3 mutations among: M41L, D67N, K70R, L210W,
T215A/C/D/E/G/H/I/L/N/S/V, K219Q/E [4, 7, 14, 15]
• K65R [30, 31, 32]
• Q151M
• Insertion at codon 69
• At least 4 mutations among: M41L, D67N, M184V/I, L210W, T215Y/F [8,
• 3 mutations among: M41L, D67N, M184V/I, L210W,
T215Y/F [8, 19, 29]
K65R [9, 11, 12]
• L74V/I [24, 25, 26, 27, 28, 29]
• Y115F
• Q151M
• Insertion at codon 69
• At least 6 mutations among: M41L, E44D, D67N, T69D/N/S, L74V/I,
• 3, 4 or 5 mutations among: M41L, E44D, D67N,
L210W, T215Y/F [13, 20, 33]
T69D/N/S, L74V/I, L210W, T215Y/F [13, 33]
K65R/E [9, 10, 11, 12, 34]
• Insertion at codon 69
• K70E [21, 22, 23]
ZDV: zidovudine, 3TC: lamivudine, FTC: emtricitabine, ddI: didanosine, d4T: stavudine, ABC: abacavir, TDF: tenofovir
September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
• L100I
• K101E
• K103H/N/S/T [1]
• V106M [2]
• E138K [12, 13]
• Y181C/I
• Y188C/L
• G190A/C/E/Q/S/T/V
• P225H
• M230L
• A98S (for HIV-1 subtype C only) [3]
E138K [13]
• L100I
• K101E
• K103H/N/S/T [1]
• V106A/M [2]
• Y181C/I
• Y188C/H/L
• G190A/C/E/Q/S/T/V
• M230L
•
At least 4 among: V90I, A98G, L100I, K101E/H/I/P/R,
3 mutations among: V90I, A98G, L100I, K101E/H/I/P/R, V106I,
V106I, V179D/F/I/L/M/T, Y181C/I, G190A/S, M230L [4, 7, 8,
V179D/F/I/L/M/T, Y181C/I, G190A/S, M230L [4, 7, 8, 9, 10, 11]
9, 10, 11]
E138K [12, 13]
E138A/G/Q/R [5, 6, 7, 8]
Y181V [5, 6]
Y181C+H221Y [7]
K101E/P [9, 13]
E138A/G/K/Q/R/S [12, 13, 14]
V179L [9]
Y181C/I/V [13]
Y188L [9]
H221Y [13]
M230I/L/V [9]
L100I + K103N/S [9, 15]
L100I + K103R + V179D [15]
EFV: efavirenz, NVP: nevirapine, ETR: etravirine, RPV : rilpivirine
September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: PROTEASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
• M46I/L
V82A/F/M/S/T [11]
• I84A/V [8]
• L90M and at least 2 among: K20M/R, L24I, V32I, M36I, I54V/L/M/T,
A71V/T, G73S/A, V77I
• At least 4 mutations among: L10F/I/M/R/V, I15A/V, K20I/M/R/T, L24I,
• 3 mutations among: L10F/I/M/R/V, I15A/V, K20I/M/R/T, L24I, I62V,
1000/100 mg BID
I62V, G73S/T, V82A/F/S/T, I84V, L90M [9]
G73S/T, V82A/F/S/T, I84V, L90M [9]
V82A/F/S/T and at least 2 among: L10I, M36I, M46I/L, I54V/L/M/T,
I84A/V [8]
A71V/T, V77I [1]
• L90M
• I50V
• V32I and I47A/V [2, 13, 14]
• At least 4 mutations among: L10F/I/V, L33F, M36I,
700/100 mg BID
I54A/L/M/S/T/V, I62V, V82A/C/F/G, I84V, L90M [2, 20]
• At least 6 mutations among: L10F/I/R/V, K20M/R, L24I, L33F, M46I/L,
• 4 or 5 mutations among: L10F/I/R/V, K20M/R, L24I, L33F, M46I/L,
I50V, F53L, I54M/L/T/V, L63P, A71I/L/V/T, V82A/F/S/T, I84V, L90M [3, 4,
I50V, F53L, I54M/L/T/V, L63P, A71I/L/V/T, V82A/F/S/T, I84V, L90M
[3, 4, 5, 21]
I47A [15, 16]
L76V [18, 19]
300/100 mg QD
N88S [28,29,30]
At least 3 mutations among: L10F/I/V, G16E, L33F/I/V, M46I/L, D60E,
I84V, I85V, L90M [7, 12, 22]
• At least a score of + 3*: 36I/L/V – 53L/W/Y + 58E + 69I/K/N/Q/R/Y +
• A score of + 2*: 36I/L/V – 53L/W/Y + 58E + 69I/K/N/Q/R/Y +
89I/M/R/T/V [10, 23]
89I/M/R/T/V [10, 23]
500/200 mg BID
At least 4 mutations among: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, •
3 mutations among: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P,
L76V, I84V, L89V [17, 24, 25, 26]
L76V, I84V, L89V [17, 24, 25, 26]
600/100 mg BID
IDV: indinavir, SQV: saquinavir, NFV: nelfinavir, RTV: ritonavir, FPV: fosamprenavir, LPV: lopinavir, ATV:atazanavir, TPV: tipranavir, DRV : darunavir

* Insufficient data for HIV-1 subtype non-B
September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: FUSION INHIBITOR
Mutations associated with resistance
• G36A/D/E/S/V [1, 2, 3, 4, 5, 6, 7]
• V38A/E/K/M
• Q40H/K/P/T
• N42D/T
• N43D/H/K/S
• L45Q/M
ENF (T20): enfuvirtide
September 2013- Version n°23
ANRS - AC 11 : RESISTANCE GROUP
GENOTYPE INTERPRETATION: INTEGRASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
• T66K [10]
• E92Q [1, 2]
• G118R [10]
• F121Y [10]
• G140A/S [7]
• Y143A/C/G/H/R/S [1, 3, 4, 5, 8, 14]
• Q148E/G/H/K/R [1, 2]
• V151L [9]
• N155H/S/T [1, 2, 9]
• E157Q [2]
• T66I/A/K [6]
• E92Q [6]
• F121Y [9]
• E138K
• G140C/S
• Y143A/C/G/H/R/S [14]
• P145S [9]
• S147G
• Q148H/R/K [6]
• V151L [9]
• N155H/S/T [6,9]
• E157Q [11]
• G118R [12,13]
• T66K [9]
• V151L [9]
• S153F
• S153Y
• Q148H/K/R + 1 mutation among: L74I or E138A/K/T or
• T66K + L74M
G140A/C/S [15]
• E92Q + N155H
• Q148H/K/R + at least 2 mutations among: L74I
or E138A/K/T or G140A/C/S [15]
• Q148R + N155H
• R263K [16]
RAL: raltegravir, EVG: elvitegravir, DTG: dolutegravir
September 2013- Version n°23
ANRS - AC 11 : RESISTANCE GROUP
GENOTYPE INTERPRETATION FOR HIV-2
NUCLEOSIDE AND NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS

• K65R : resistance to ddI, TDF, ABC [1]
• Q151M : all NRTI except 3TC and FTC [1]
• M184V : resistance to 3TC/FTC [1]
• S215A/C/F/L/P/Y : resistance to AZT and d4T [1]
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

• Naturally resistant to all NNRTI [2, 3]

PROTEASE INHIBITORS

• Naturally resistant to APV and fosAPV [2, 3]
Contradictory data for ATV , TPV [2, 4]

FUSION INHIBITOR

• Naturally resistant to T20 [2, 3]
INTEGRASE INHIBITORS

• Y143C/H/R : resistance to raltegravir [7]
• Q148K/R : resistance to raltegravir [5]
• N155H : resistance to raltegravir [6]
September 2013- Version n°23
REFERENCES
Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
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Source: http://www.hivfrenchresistance.org/2013/Algo-sep-2013.pdf