HIVdb version 8.1.1 (last updated 2016-09-23)

INSTI Resistance Mutation Comments

(PI · NRTI · NNRTI)
MutationTypeComment
H51YAccessoryH51Y is a rare non-polymorphic accessory mutation selected in patients receiving RAL and EVG and in vitro by DTG. H51Y reduces EVG susceptibility 2 to 3-fold. It does not reduce RAL or DTG susceptibility.
T66AMajorT66A is a non-polymorphic mutation selected in patients receiving EVG and RAL, usually in combination with other INSTI-resistance mutations. It reduces EVG susceptibility ~5-fold. It does not appear to reduce RAL or DTG susceptibility.
T66IMajorT66I is a non-polymorphic mutation selected in patients receiving EVG and RAL. It reduces EVG susceptibility ~10-fold but does not appear to reduce RAL or DTG susceptibility.
T66KMajorT66K is a non-polymorphic mutation selected in patients receiving EVG. It is associated with high-level EVG resistance, intermediate/high-level RAL resistance, and low-level DTG resistance.
L74MIOtherL74M/I are highly polymorphic accessory mutations commonly selected by each of the INSTIs. In ARV-naive patients, L74M occurs in 0.5% to 10% of patients and L74I occurs in 3% to 20% of patients depending on subtype. Alone, L74M/I have minimal, if any, effect on INSTI susceptible. However, they appear to contribute reduced susceptibility to each of the INSTIs when they occur with primary INSTI-resistance mutations.
E92GMajorE92G is a rare non-polymorphic mutationt that has been selected in patients receiving EVG. It reduces EVG susceptibility ~10-fold. It does not reduce RAL or DTG susceptibility.
E92QMajorE92Q is a common non-polymorphic mutation selected in patients receiving RAL and EVG. It reduces RAL susceptibility 5 to 10-fold and EVG susceptibility ~30-fold. It is selected in vitro by DTG and reduces DTG susceptibility ~1.5-fold.
E92VMajorE92V is a rare non-polymorphic mutation selected in vitro by an investigational INSTI. It reduces RAL and EVG susceptibility by 10-fold and 40-fold, respectively.
Q95KAccessoryQ95K is a non-polymorphic accessory mutation selected in patients receiving RAL and in vitro by EVG. Alone, it has little if any effect on INSTI susceptibility.
T97AAccessoryT97A is a polymorphic accessory mutation that, depending on subtype, occurs in 1% to 5% of viruses from untreated persons. It is selected by RAL and EVG. Alone, it has minimal effects on INSTI susceptibility but in combination with other primary resistance mutations, particularly Y143C/R, it synergistically reduces susceptibility to EVG and RAL.
G118RMajorG118R is an extremely rare non-polymorphic mutation selected in one patient receiving RAL and two patients receiving DTG It has also been selected in vitro by DTG. Its reported effect on in vitro susceptibility has been highly variable ranging from having no effect to causing >5-fold reduced susceptibility to each of the INSTIs.
F121YMajorF121Y is a non-polymorphic mutation selected in vitro by RAL and EVG. It has been reported rarely in patients receiving RAL. It reduces susceptibility to RAL by ~10-fold and to EVG by ~30-fold. It may also reduce DTG susceptibility.
A128TAccessoryA128T is a non-polymorphic mutation selected in vitro by EVG. It does not appear to reduce INSTI susceptibility.
E138DOtherE138D is a polymorphism that occurs in 1% to 2% of viruses from INSTI-naive patients. It does not appear to be selected by INSTIs or to reduce INSTI susceptibility.
E138KATMajorE138K/A are non-polymorphic mutations selected in patients receiving RAL, EVG, and DTG. They usually occur in combination with Q148 mutations. Alone they do not reduce INSTI susceptibility. However, they are associated with >100-fold reduced RAL and EVG susceptibility and up to 10-fold reduced DTG susceptibility when they occur in combination with Q148 mutations. E138T is a rare nonpolymorphic INSTI-selected mutation that appears to have an effect similar to E138K/A.
G140SACMajorG140S/A/C are non-polymorphic mutations that usually occur with Q148 mutations in patients receiving RAL or EVG. Alone, they do not reduce INSTI susceptibility. However, in combination with Q148 mutations they are associated with a >100-fold reduction in RAL and EVG susceptibility and an up to 10-fold reduction in DTG susceptibility.
Y143CRMajorY143C/R are non-polymorphic mutations selected by RAL. Alone, Y143C and Y143R reduce RAL susceptibility ~5 and 20-fold, respectively. In combination with T97A and other accessory mutations they reduce RAL susceptibility >100-fold. Alone, Y143C/R have minimal effects on EVG susceptibility. However, they are associated with ~10-fold reduced EVG susceptibility when they occur in combination with one or more INSTI-resistance mutations. Y143 mutations do not reduce DTG susceptibility.
Y143HMajorY143C/R are non-polymorphic mutations selected by RAL. Alone, Y143C and Y143R reduce RAL susceptibility ~5 and 20-fold, respectively. In combination with T97A and other accessory mutations they reduce RAL susceptibility >100-fold. Y143H is a less-common mutation at this position that is likely a transitional mutation between the wildtype Y amino acid and the mutant R which differs from Y by two bases.
Y143KGSAMajorY143K/G/S/A are extremely rare mutations that reduce RAL susceptibility ~5 to 10-fold.
P145SMajorP145S is a rare non-polymorphic mutation selected in vitro by EVG and rarely in patients receiving EVG. It causes high-level resistance to EVG but not to RAL or DTG.
Q146PMajorQ146P is a rare non-polymorphic mutation selected in vitro by EVG. It reduces EVG susceptibility ~10-fold.
S147GMajorS147G is a non-polymorphic mutation selected in patients receiving EVG. It reduces EVG susceptibility 5 to 10-fold. It does not reduce RAL or DTG susceptibility.
Q148HKRMajorQ148H/K/R are non-polymorphic mutations selected by RAL and EVG. Alone, Q148H reduces RAL and EVG susceptibility ~5 to 10-fold. Alone, Q148R/K reduce RAL and EVG susceptibility ~30 to 100-fold. In combination with G140S/A or E138K/A, they reduce RAL and EVG susceptibility >100-fold. Alone, Q148H/K/R have minimal effects on DTG susceptibility. In combination with G140S/A/C and/or E138K/A, they reduce DTG susceptibility up to 10-fold.
Q148NMajorQ148H/K/R are non-polymorphic mutations selected by RAL and EVG. In combination with G140S/A or E138K/A, they reduce RAL and EVG susceptibility >100-fold. In combination with G140S/A/C and/or E138K/A, they reduce DTG susceptibility >10-fold. Q148N is a rare INSTI-selected mutation that causes ~3-fold reduced EVG susceptibility and may represent a reversion from Q148H or Q148K.
V151AAccessoryV151A is an extremely rare non-polymorphic mutation selected in vitro by an investigational INSTI. It is associated with ~4-fold and 12-fold reduced susceptibility to RAL and EVG, respectively.
V151IOtherV151I occurs in 5% of subtype B viruses from ARV-naive patients but is nonpolymorphic in most other subtypes. It is selected in patients receiving RAL and in vitro by EVG. It appears to have little or no effect on INSTI susceptibility.
V151LMajorV151L is an extremely rare non-polymorphic mutation selected in vitro by early investigational INSTIs but not in patients receiving current INSTIs. It reduces susceptibility to RAL, EVG, and DTG by ~10-fold, 40-fold, and 3-fold, respectively.
S153YFAccessoryS153Y/F are extremely rare non-polymorphic mutations selected in vitro by EVG and DTG. S153Y/F reduce RAL and DTG susceptibility ~2-fold and EVG susceptibility ~4-fold.
N155HMajorN155H is a non-polymorphic mutation selected in patients receiving RAL and EVG. Alone, it reduces RAL and EVG susceptibility ~15-fold and 30-fold, respectively. N155H has been selected by DTG in RAL-experienced patients but alone does not reduce DTG susceptibility.
N155STMajorN155H is a non-polymorphic mutation selected in patients receiving RAL and EVG. Alone, it reduces RAL and EVG susceptibility ~15-fold and 30-fold, respectively. N155H has been selected by DTG in RAL-experienced patients but alone does not reduce DTG susceptibility. N155S/T are rare non-polymorphic mutations selected in vitro by investigational INSTIs. They reduce RAL and EVG susceptibility somewhat less than does N155H.
E157QAccessoryE157Q is a polymorphic mutation selected in patients receiving RAL and in vitro by EVG. It has also been reported in a patient with virological failure on a DTG-containing regimen. It appears to reduce RAL and EVG susceptibility by 2- to 3-fold and to increase DTG susceptibility.
G163RKAccessoryG163R/K occur in 5% to 10% of subtype F viruses from ARV-naive patients but are otherwise non-polymorphic. They are commonly selected in patients receiving RAL. Their effect on INSTI susceptibility has not been well studied.
S230NOtherS230N is a polymorphism that is not associated with reduced INSTI susceptibility.
S230RAccessoryS230R is a non-polymorphic accessory mutation selected by RAL and EVG. It appears to have minimal, if any, effect on INSTI susceptibility.
R263KAccessoryR263K is a rare non-polymorphic mutation selected in patients receiving RAL and DTG and in vitro by EVG and DTG. It reduces RAL, DTG, and EVG susceptibility by ~2-fold, 2-fold, and 4-fold, respectively.