HIVdb version 9.0 (last updated on 2021-02-22)

INSTI Resistance Comments

(PI · NRTI · NNRTI · INSTI)
ConditionComment/
Mutation Type
Comment
49GAccessoryA49G is a rare nonpolymorphic IN mutation that has been reported in combination with one or more INSTI-resistance mutations in two persons receiving DTG.
50IOtherM50I is a polymorphic mutation selected in vitro by DTG and BIC in combination with R263K. It appears to contribute to reduced DTG susceptibility in combination with R263K.
51YAccessoryH51Y is a rare non-polymorphic accessory mutation selected in patients receiving RAL and EVG and in vitro by DTG. H51Y minimally reduces EVG and possibly CAB 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 moderate reduction in EVG susceptibility but does not appear to reduce susceptibility to other INSTIs.
66IMajorT66I is a non-polymorphic mutation selected in patients receiving EVG, RAL, and DTG. It reduces EVG susceptibility about 10-fold but does not reduce susceptibility to other INSTIs.
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 and CAB resistance. Its effect on BIC is not known.
74MIFOtherL74M is a polymorphic accessory mutations commonly selected by each of the INSTIs. In ARV-naive patients, L74M occurs in 0.5% to 5% of patients depending on subtype. L74I occurs in 4% to 40% of patients depending on subtype. L74I is the consensus amino acid for subtype A6 and does not appear to be selected by INSTI therapy. Alone, L74M/I have minimal, if any, effect on INSTI susceptibility. However, L74M and possibly L74I reduce susceptibility to each of the INSTIs when they occur with major INSTI-resistance mutations. L74F is a rare nonpolymorphic mutation which also contributes reduced susceptibility when it occurs with other 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 susceptibility to RAL, DTG, or BIC.
92QMajorE92Q 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. It does not appear to reduce BIC susceptibility.
92VMajorE92V is a rare non-polymorphic mutation selected in vitro by an investigational INSTI. It causes high-level resistance to EVG and intermediate resistance to RAL.
95KAccessoryQ95K is a non-polymorphic INSTI-selected mutation. Alone, it has little if any effect on INSTI susceptibility.
97AAccessoryT97A is a polymorphic INSTI-selected mutation that, depending on subtype, occurs in 1% to 5% of viruses from untreated persons. Alone, it has minimal effects on INSTI susceptibility but in combination with other major resistance mutations, it synergistically reduces susceptibility to each of the INSTIs.
118RMajorG118R is a rare non-polymorphic mutation selected in patients receiving RAL and DTG and in vitro by DTG. Depending on the mutational context it causes 3 to 30-fold reduced susceptibility to each of the INSTIs.
119ROtherS119R is a polymorphic mutation that is weakly selected by INSTIs usually in combination with several major INSTI-associated DRMs. Alone, it has little, if any effect, on INSTI susceptibility .
121COtherF121C is a rare mutation; preliminary data suggests it confers high level phenotypic resistance to RAL, EVG, and CAB.
121YMajorF121Y is a non-polymorphic mutation selected in vitro by RAL and EVG. It has been reported rarely in patients receiving RAL. It causes intermediate to high-level reductions in RAL and EVG susceptibility but does not appear to reduce DTG or BIC susceptibility. F121C is an exceedingly rare mutation that has been reported to cause high-level resistance to RAL, EVG, and CAB but low-level reduced susceptibility to DRG and BIC.
128TAccessoryA128T is a relatively nonpolymorphic possible INSTI-selected mutation, which 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.
140RMajorG140R is a nonpolymorphic mutation reported in n macaques receiving CAB pre-exposure prophylaxis and in a person receiving simplification therapy with RPV/CAB. It reduces CAB susceptibility by 7-fold.
140SACMajorG140S/A/C are non-polymorphic mutations that usually occur with Q148 mutations. Alone, they have minimal effects on INSTI susceptibility. 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. Their appearance may suggest that a Q148 mutation may have once been present.
142TAccessoryP142T is a rare nonpolymorphic mutation selected in vitro and in vivo by RAL. It usually occurs in combination with other INSTI-resistance mutations. Its effect on susceptibility has not been studied.
143CRHMajorY143C/R/H are non-polymorphic mutations associated with high-level RAL resistance. Alone, they have minimal effects on EVG susceptibility. However, they are associated with intermediate reductions in EVG susceptibility when they occur in combination with one or more accessory INSTI-resistance mutations. Y143 mutations do not reduce susceptibility to DTG, BIC, or CAB.
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 any other INSTI.
146PMajorQ146P is a rare non-polymorphic mutation selected in vitro by EVG which causes low-to-intermediate reductions in EVG and CAB susceptibility.
147GMajorS147G is a non-polymorphic mutation selected primarily in patients receiving EVG and less commonly in patients receiving RAL and DTG. It moderately reduces EVG susceptibility. It does not reduce RAL, DTG, or BIC susceptibility.
148HKRMajorQ148H/K/R are non-polymorphic mutations selected by RAL, EVG, and rarely DTG. They nearly always occur in combination with G140A/S or E138K. In this setting they are associated with near complete resistance to RAL and EVG, high-levels of reduction in CAB susceptibility, and intermediate reductions in DTG and BIC susceptibility. The presence of Q148H/K/R plus two INSTI DRMs is usually associated with high-level reductions in susceptibility to all INSTIs.
148NMajorQ148H/K/R are non-polymorphic mutations selected by RAL, EVG, and rarely DTG. They nearly always occur in combination with G140A/S or E138K. In this setting they are associated with near complete resistance to RAL and EVG, high-levels of reduction in CAB susceptibility, and intermediate reductions in DTG and BIC susceptibility. The presence of Q148H/K/R plus two INSTI DRMs is usually associated with high-level reductions in susceptibility to all INSTIs. Q148N is a rare INSTI-selected mutation that causes ~3-fold reduced EVG susceptibility and may represent a reversion from Q148H or Q148K.
149AAccessoryG149A selected in vivo by DTG in RAL experienced patients. It appears to have no effect by itself but in combination with mutations at positions 140 and 148, it reduces DTG susceptibility.
151AAccessoryV151A is an extremely rare non-polymorphic mutation associated with minimally reduced susceptibility to RAL and EVG.
151IOtherV151I is an accessory INSTI selected mutation that occurs in 1% to 5% of viruses from ARV-naive patients depending on subtype. Alone, it appears to have little or no effect on INSTI susceptibility.
151LMajorV151L is an extremely rare non-polymorphic mutation that confers intermediate / high-level reduced susceptibility to RAL and EVG and low-level reduced susceptibility to DTG.
153YFAccessoryS153Y/F are rare non-polymorphic mutations selected in vitro by EVG, DTG, and BIC. 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 is associated with high-level reductions in RAL and EVG susceptibility. It causes low-level reductions in DTG susceptibility.
155STMajorN155H is a non-polymorphic mutation selected in patients receiving RAL, EVG, and rarely DTG. It is associated with high-level reductions in RAL and EVG susceptibility. It causes low-level reductions 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 effect on INSTI susceptibility.
163RKAccessoryG163R/K are polymorphic in subtype F viruses from ARV-naive patients but are otherwise non-polymorphic. They are common INSTI-selected mutations. 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 mutation selected by RAL, EVG, and DTG. It possibly causes low-level reductions in DTG susceptibility.
232NAccessoryD232N is a common nonpolymorphic accessory mutation selected in patients receiving RAL and EVG.
263KMajorR263K is selected in vitro by EVG, DTG, and BIC, and in patients receiving DTG. It reduces DTG and BIC susceptibility about 2-fold and EVG susceptibility somewhat more.
Level 4 CABThis virus is predicted to have intermediate-level reduced susceptibility to CAB. The use of the combination of CAB/RPV should be considered to be contraindicated.
Level 3 CABThis virus is predicted to have low-level reduced susceptibility to CAB. The use of the combination of CAB/RPV should be considered to be relatively contraindicated.
Level 5 DTGThere is evidence for high-level DTG resistance. If DTG is used, it should be administered twice daily.
Level 4 DTGThere is evidence for intermediate DTG resistance. If DTG is used, it should be administered twice daily.
Level 3 DTGThere is evidence for low-level DTG resistance. If DTG is used, it should be administered twice daily.