Resistance primer

Open the interactive resistance explorer →

How genotypes are scored here

Each mutation adds a penalty score for each drug; some combinations add more. The total maps to a level, modelled on the Stanford HIVdb approach:

1Susceptible score < 10
2Potential low-level resistance 10–14
3Low-level resistance 15–29
4Intermediate resistance 30–59
5High-level resistance ≥ 60

A drug's contribution to the genotypic susceptibility score (GSS) is 1 (levels 1–2), 0.75 (3), 0.5 (4) or 0 (5). After virological failure, aim for at least two fully active drugs, or a fully active high-barrier anchor (dolutegravir or boosted darunavir).

The table is abridged and approximate, for teaching. Use the laboratory report or Stanford HIVdb clinically.

Signature mutations

M184VSelected by lamivudine/emtricitabine; reduces viral fitness and increases tenofovir and zidovudine susceptibility.
M184IUsually precedes M184V; same phenotype.
K65RSelected by tenofovir (and abacavir); reduces tenofovir/abacavir/3TC activity but increases zidovudine susceptibility.
K103NThe classic efavirenz/nevirapine mutation; rilpivirine, doravirine and etravirine stay active.
E138KRilpivirine signature mutation, often with M184I.
Y181CBroad first-generation NNRTI resistance; reduces rilpivirine and etravirine.
Y188LHigh-level resistance to doravirine, efavirenz and rilpivirine.
Q148HIntegrase pathway; with G140S it reduces dolutegravir/bictegravir and abolishes raltegravir.
N155HRaltegravir/elvitegravir pathway; second-generation INSTIs largely retained alone.
R263KSelected by dolutegravir in INSTI-naive patients; low-to-intermediate dolutegravir resistance.
G118RRare dolutegravir-selected mutation with broad INSTI resistance.
I50LAtazanavir signature mutation; increases susceptibility to other PIs.
I84VBroad PI mutation; contributes to darunavir resistance with others.
L76VDarunavir resistance-associated mutation.

Reverse transcriptase (RT)

MutationAbacavirZidovudineEmtricitabineLamivudineTenofovir disoproxilDoravirineEfavirenzEtravirineRilpivirine
M41L 5 15 5
K65R 45 -10 30 30 50
K65N 30 15 15 30
D67N 5 15 5
T69ins 60 60 30 30 60
K70R 5 30 5
K70E 15 10 10 30
L74V 30
L74I 30
Y115F 30 10
Q151M 60 60 10 10 15
M184V 15 -10 60 60 -10
M184I 15 -10 60 60 -10
L210W 5 30 5
T215Y 10 60 10
T215F 10 60 10
K219Q 5 15
K219E 5 15
A98G 10 15 10 15
L100I 15 60 30 60
K101E 15 30 30 45
K101P 15 60 60 60
K103N 60
K103S 45
V106A 45 30
V106M 30 60
V108I 10 10
E138A 10 15
E138G 10 15
E138K 10 10 15 45
E138Q 10 15
V179D 10 10 10 10
Y181C 10 30 30 45
Y181I 15 30 60 60
Y181V 15 30 60 60
Y188L 60 60 10 60
Y188H 15 30 15
G190A 10 45 10 15
G190S 15 60 10 15
G190E 60 60 45 60
H221Y 10 15
P225H 10 45
F227C 60 15 30 30
F227L 15
M230L 30 45 30 60
Y318F 30

Combination penalties

  • M41L + T215Y/T215F → ABC +5, AZT +15, TDF +5
  • M41L + L210W + T215Y/T215F → ABC +10, AZT +10, TDF +10
  • D67N + K70R + K219Q/K219E → ABC +5, AZT +10, TDF +5

Integrase (IN)

MutationBictegravirCabotegravirDolutegravirRaltegravir
T66I 10 15
T66K 15 15 15 30
E92Q 10 10 10 30
T97A 10 5 10
G118R 30 45 30 60
E138A 10 10 10 15
E138K 10 10 10 15
E138T 10 10 10 15
G140A 10 10 10 15
G140C 10 10 10 15
G140S 10 10 10 15
Y143C 10 45
Y143H 10 45
Y143R 10 60
Q148H 15 30 15 60
Q148K 30 45 30 60
Q148R 25 45 25 60
N155H 10 15 10 60
R263K 30 30 30 15

Combination penalties

  • G140S/G140A/G140C + Q148H/Q148K/Q148R → BIC +30, CAB +40, DTG +30
  • E138K/E138A/E138T + Q148H/Q148K/Q148R → BIC +25, CAB +35, DTG +25
  • N155H + Q148H/Q148K/Q148R → BIC +20, CAB +20, DTG +20

Protease (PR)

MutationAtazanavirDarunavir
V32I 15 15
L33F 5 5
M46I 10
M46L 10
I47V 10 15
G48V 30
I50L 60
I50V 20
I54L 15 20
I54M 15 20
L76V 20
V82A 15
V82F 10 10
I84V 60 15
N88S 60
L90M 20