Sierra version 2.2.5-1 (last updated 2018-04-23)
HIVdb version 8.5 (last updated 2018-04-16)

INSTI Resistance Comments

(PI · NRTI · NNRTI)
ConditionComment/
Mutation Type
Comment
51YAccessoryH51Y is a rare non-polymorphic accessory mutation selected in patients receiving RAL and EVG and in vitro by DTG. H51Y minimally reduces EVG susceptibility (~2 to 3-fold). It does not reduce RAL or DTG susceptibility.
66AMajorT66A is a non-polymorphic mutation selected in patients receiving EVG and RAL, usually in combination with other INSTI-resistance mutations. It causes a moderatereduction in EVG susceptibility (~5-fold). It does not appear to reduce RAL or DTG susceptibility.
66IMajorT66I is a non-polymorphic mutation selected in patients receiving EVG and RAL. It reduces EVG susceptibility by about 10-fold but does not reduce RAL, DTG, or BIC susceptibility.
66KMajorT66K 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. Its effect on BIC is not known.
74MIOtherL74M/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 susceptibility. However, they contribute reduced susceptibility to each of the INSTIs when they occur with major INSTI-resistance mutations.
92GMajorE92G is a rare non-polymorphic mutation that has been selected in patients receiving EVG. It moderately reduces EVG susceptibility but does not reduce RAL or DTG susceptibility.
92QMajorE92Q is a common non-polymorphic mutation selected in patients receiving RAL and EVG. It causes intermediate and high-level reductions in RAL and EVG susceptibility, respectively. It is selected in vitro by DTG and reduces DTG susceptibility <=1.5-fold. Its effect on BIC is uncertain.
92VMajorE92V is a rare non-polymorphic mutation selected in vitro by an investigational INSTI. It causes intermediate and high-level reductionss in EVG and RAL susceptibility, respectively.
95KAccessoryQ95K 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.
97AAccessoryT97A is a polymorphic accessory mutation that, depending on subtype, occurs in 1% to 5% of viruses from untreated persons. It is selected primarily by RAL and EVG. Alone, it has minimal effects on INSTI susceptibility but in combination with other major resistance mutations, it synergistically reduces susceptibility to EVG, RAL, DTG, and possibly BIC.
118RMajorG118R is an extremely rare non-polymorphic mutation selected in patients receiving RAL and 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. Data are not available for BIC.
121YMajorF121Y 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.
128TAccessoryA128T is a non-polymorphic mutation selected in vitro by EVG. It does not appear to reduce INSTI susceptibility.
138DOtherE138D 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.
138KATMajorE138K/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, when they occur in combination with Q148 mutations, they are associated with high-level resistance to RAL and EVG and intermediate reductions in DTG and BIC susceptibility. E138T is an uncommon nonpolymorphic INSTI-selected mutation that appears to have an effect similar to E138K/A.
140SACMajorG140S/A/C are non-polymorphic mutations that usually occur with Q148 mutations in patients receiving RAL or EVG. Alone, they minimally reduce susceptibility to RAL and EVG. However, in combination with Q148 mutations they are associated with high-level resistance to RAL and EVG and intermediate reductions in DTG and BIC susceptibility.
143CRMajorY143C/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 intermediate to high-level reductions in EVG susceptibility (~10-fold) when they occur in combination with one or more accessory INSTI-resistance mutations. Y143 mutations do not reduce DTG or BIC susceptibility.
143HMajorY143C/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 the wildtype Y by two nucleotides).
143KGSAMajorY143K/G/S/A are rare mutations that cause intermediate reductions in RAL susceptibility. When they occur in combination with other accessory mutations, they may also cause low-level reductions in EVG susceptibility.
145SMajorP145S 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.
146PMajorQ146P is a rare non-polymorphic mutation selected in vitro by EVG. It causes intermediate to high-level reductions in EVG susceptibility (~5 to 10-fold).
147GMajorS147G is a non-polymorphic mutation selected in patients receiving EVG. It moderately reduces EVG susceptibility (5-10-fold). It does not reduce RAL or DTGsusceptibility.
148HKRMajorQ148H/K/R are non-polymorphic mutations selected by RAL, EVG, and rarely DTG. Alone, Q148H moderately reduces RAL and EVG susceptibility ~5 to 10-fold. Alone, Q148R/K reduce RAL and EVG susceptibility ~30 to 100-fold. However, Q148H/K/R usually occur In combination with G140S/A or E138K/A/T, in which case they reduce RAL and EVG susceptibility >100-fold. Alone, Q148H/K/R have minimal effects on DTG and BIC susceptibility. In combination with G140S/A/C and/or E138K/A/T, they cause moderate to high level reductions in DTG and BIC susceptibility.
148NMajorQ148H/K/R are non-polymorphic mutations selected by RAL, EVG, and rarely DTG. Alone, Q148H moderately reduces RAL and EVG susceptibility ~5 to 10-fold. Alone, Q148R/K reduce RAL and EVG susceptibility ~30 to 100-fold. However, Q148H/K/R usually occur In combination with G140S/A or E138K/A/T, in which case they reduce RAL and EVG susceptibility >100-fold. Alone, Q148H/K/R have minimal effects on DTG and BIC susceptibility. In combination with G140S/A/C and/or E138K/A/T, they cause moderate to high level reductions in DTG and BIC susceptibility. Q148N is a rare INSTI-selected mutation that causes ~3-fold reduced EVG susceptibility and may represent a reversion from Q148H or Q148K.
151AAccessoryV151A is an extremely rare non-polymorphic mutation selected in vitro by an investigational INSTI. It is associated with minimally reduced susceptibility to RAL and EVG.
151IOtherV151I 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.
151LMajorV151L is an extemely rare non-polymorphic mutation selected in vitro by early investigational INSTIs but not in patients receiving current INSTIs. It confers intermediate / high-level reduced susceptibility to RAL and EVG and low-level reduced susceptibility to DTG.
153YFAccessoryS153Y/F are extremely rare non-polymorphic mutations selected in vitro by EVG and DTG. S153Y/F reduce RAL, DTG, and possibly BIC susceptibility about 2-fold and EVG susceptibility about 4-fold.
155HMajorN155H is a non-polymorphic mutation selected in patients receiving RAL, EVG, and rarely DTG. It reduces RAL and EVG susceptibility >15-fold. It causes minimal if any clinically significant reduction in DTG susceptibility.
155STMajorN155H is a non-polymorphic mutation selected in patients receiving RAL, EVG, and rarely DTG. It reduces RAL and EVG susceptibility >15-fold. It causes minimal if any clinically significant reduction in DTG susceptibility. N155S/T are extremely rare non-polymorphic mutations selected in vitro by investigational INSTIs. They reduce RAL and EVG susceptibility somewhat less than does N155H.
157QAccessoryE157Q is a polymorphic mutation selected in patients receiving RAL and EVG. It appears to have little, if any, effect on INSTI susceptibility.
163RKAccessoryG163R/K are polymorphic in subtype F viruses from ARV-naive patients but are otherwise non-polymorphic. They are commonly selected in patients receiving RAL and possibly EVG. Alone, they have little, if any, effect on INSTI susceptibility.
230NOtherS230N is a polymorphism that is not associated with reduced INSTI susceptibility.
230RAccessoryS230R is a non-polymorphic accessory mutation selected by RAL, EVG, and rarely DTG. It appears to have minimal, if any, effect on INSTI susceptibility.
263KAccessoryR263K is an uncommon mutation selected in patients receiving RAL and DTG and in vitro by EVG, DTG, and BIC. It reduces EVG susceptibility by about 4-fold, and RAL, DTG, and BIC susceptibility by about 2-fold.
Level 5 DTGDosageThere is evidence for high-level DTG resistance. If DTG is used, it should be administered twice daily.
Level 4 DTGDosageThere is evidence for intermediate DTG resistance. If DTG is used, it should be administered twice daily.
Level 3 DTGDosageThere is evidence for low-level DTG resistance. If DTG is used, it should be administered twice daily.