INI Resistance Notes
Last updated on Feb 28, 2014
| Resistance Matrix | Resistance Mutation Comments | Resistance Mutation Scores |
| Position | Cons | AA | Comment |
| 51 | H | Y | H51Y is an uncommon nonpolymorphic accessory mutation selected in patients receiving RAL and EVG. It is also selected in vitro by EVG and DTG. Alone, H51Y reduces EVG susceptibility 2 to 3-fold. It does not reduce RAL or DTG susceptibility. However, the combination of H51Y and R263K is associated with ~5-fold reduced DTG susceptibility. |
| 66 | T | A | T66A is a nonpolymorphic mutation selected in patients receiving EVG and RAL, usually occurring in combination with other INI-resistance mutations. It reduces EVG susceptibility by ~10-fold. It does not appear to reduce RAL or DTG susceptibility. |
| 66 | T | I | T66I is a nonpolymorphic mutation selected in patients receiving EVG. T66I decreases EVG susceptibility by ~15-fold but does not reduce RAL or DTG susceptibility. |
| 66 | T | K | T66K is a nonpolymorphic mutation selected in patients receiving EVG. It is associated with 40 to 80-fold reduced EVG susceptibility, 10 to 20-fold reduced RAL susceptibility and 2-fold reduced DTG susceptibility. |
| 68 | L | V | L68V is a polymorphic accessory mutation reported in patients receiving EVG. It may synergistically reduce EVG susceptibility in combination with E92Q. |
| 74 | L | M | L74M is a polymorphic accessory mutation selected in patients receiving RAL, EVG, and DTG. Alone, it does not reduce INI susceptibility. But when it occurs in combination with other INI-resistance mutations, L74M contributes to reduced RAL, EVG, and DTG susceptibility. |
| 92 | E | G | E92G is a nonpolymorphic mutation selected in patients receiving EVG. It reduces EVG susceptibility ~10-fold. It does not reduce RAL or DTG susceptibility. |
| 92 | E | Q | E92Q is a common nonpolymorphic mutation selected in patients receiving RAL and EVG. It reduces RAL susceptibility by 5 to 10-fold and EVG susceptibility by ~30-fold. It is the most common INI-resistance mutation associated with virological failure on an EVG-containing regimen. It is selected in vitro by DTG and reduces DTG susceptibility by ~1.5-fold. |
| 92 | E | V | E92V is a nonpolymorphic mutation selected in vitro by the investigational INI GS-9160. It reduces RAL susceptibility by 10-fold and EVG susceptibility by 40-fold. |
| 95 | Q | K | Q95K is a nonpolymorphic accessory INI-resistance mutation selected in patients receiving RAL and in vitro by EVG. Alone, it has little if any effect on INI susceptibility. |
| 97 | T | A | T97A is a polymorphic accessory INI-resistance 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 if any effect on INI susceptibility but in combination with Y143C/R it markedly reduces RAL susceptibility. |
| 114 | H | Y | H114Y is an extremely rare nonpolymorphic mutation selected in vitro by EVG. It does not appear to be associated with significantly reduced INI susceptibility. |
| 118 | G | R | G118R is an extremely rare nonpolymorphic mutation that has been selected by RAL in a patient with a CRF02_AG virus. When G118R occurred in combination with L74M in this virus, RAL susceptibility was reduced by ~10-fold and EVG susceptibility by ~3-fold. G118R has been selected in vitro by DTG and reported to reduce DTG susceptibility by 3-fold in a biochemical assay. |
| 121 | F | Y | F121Y is a nonpolymorphic mutation that is selected in vitro by RAL and EVG. It has been observed in one patient receiving RAL. It reduces susceptibility to RAL by about 5-fold and to EVG by about 10-fold. It does not appear to reduce DTG susceptibility. $listMutsIn{121(NOT Y)} is an unusual mutation at this position. |
| 128 | A | T | A128T is a nonpolymorphic mutation selected in vitro by EVG. It does not appear to reduce INI susceptibility. |
| 138 | E | D | E138D is a polymorphism that occurs in 1% to 2% of viruses from INI-naive patients. It does not appear to be selected by INIs or to reduce INI susceptibility. |
| 138 | E | KA | E138K/A are nonpolymorphic accessory resistance mutations selected in patients receiving RAL, EVG, and DTG. They usually occur in combination with Q148 mutations. Alone they do not reduce INI susceptibility. However they are associated with >100-fold reduction in RAL and EVG susceptibility and up to 10-fold reduced DTG susceptibility when they occur in combination with Q148 mutations. |
| 140 | G | SAC | G140S/A/C are nonpolymorphic mutations that usually occur with Q148 mutations in patients receiving RAL or EVG. Alone, they do not reduce INI susceptibility. However, in combination with Q148 mutations they are associated with a >100-fold reduction in RAL and EVG susceptibility and up to 10-fold reduction DTG susceptibility. |
| 143 | Y | CR | Y143C/R are nonpolymorphic mutations selected by RAL. Alone, Y143C and Y143R reduce RAL susceptibility by ~5 and 20-fold, respectively, but in combination with T97A or other accessory mutations they reduce RAL susceptibility >100-fold. Alone, Y143C/R have minimal effects on EVG susceptibility. However, they are associated with 10 to 20-fold reduced EVG susceptibility when they occur in combination with greater or equal than 2 accessory INI-resistance mutations (such as L74M, T97A, G163R, and S230R). Y143 mutations do not reduce DTG susceptibility. |
| 143 | Y | H | Y143C/R are nonpolymorphic mutations selected by RAL. Alone, Y143C and Y143R reduce RAL susceptibility by ~5 and 20-fold, respectively, but in combination with T97A or other accessory mutations they reduce RAL susceptibility >100-fold. Y143H is a less-common mutation at this position. It is likely a transitional mutation between the wildtype Y and the 2-base pair mutant R. |
| 143 | Y | KGSA | Y143K/G/S/A are extremely rare mutations that reduce RAL susceptibility by 5 to 10-fold. |
| 145 | P | S | P145S is a rare nonpolymorphic mutation that has been selected in vitro by EVG and rarely in patients receiving EVG. It causes high-level resistance to EVG but not to RAL or DTG. |
| 146 | Q | P | Q146P is a rare nonpolymorphic mutation that has been selected in vitro by EVG. It reduces EVG susceptibility by ~10-fold. |
| 147 | S | G | S147G is a nonpolymorphic mutation selected in patients receiving EVG. It reduces EVG susceptibility 5 to 10-fold. It does not reduce RAL or DTG susceptibility. |
| 148 | Q | HKR | Q148H/K/R are nonpolymorphic mutations selected by RAL and EVG. Alone, Q148H reduces RAL and EVG susceptibility 5 to 10-fold. Q148R/K reduce RAL and EVG susceptibility 30 to 100-fold. When Q148H/K/R occur 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 E138K/A +/- G140S/A/C they cause >10-fold reduced susceptibility to DTG. |
| 151 | V | A | V151A is an extremely rare nonpolymorphic mutation selected in vitro by an investigational INI. It has been reported to reduce susceptibility to RAL by 4-fold and to EVG by 12-fold. |
| 151 | V | I | V151I is a polymorphic mutation selected in patients receiving RAL and in vitro by EVG. It appears to have little or no effect on INI susceptibility. |
| 151 | V | L | V151L is an extremely rare nonpolymorphic mutation selected in vitro by early investigational INIs but not in patients receiving current INIs. It reduces susceptibility to RAL, EVG, and DTG by ~10, ~40, and 3-fold, respectively. |
| 153 | S | YF | S153Y/F are extremely rare nonpolymorphic mutations selected in vitro by EVG (S153Y) and DTG (S153Y/F). S153Y/F reduce RAL and DTG susceptibility by ~2-fold and EVG susceptibility by ~4-fold. |
| 155 | N | H | N155H is a nonpolymorphic mutation selected in patients receiving RAL and EVG. Alone, it reduces RAL susceptibility ~15-fold and EVG susceptibility ~30-fold. Susceptibility is further reduced when N155H occurs in combination with E92Q and other primary or accessory INI-resistance mutations. N155H has been selected by DTG in RAL-experienced patients but does not reduce DTG susceptibility by itself. |
| 155 | N | ST | N155H is a nonpolymorphic mutation selected in patients receiving RAL and EVG. Alone, it reduces RAL susceptibility ~15-fold and EVG susceptibility ~30-fold. Susceptibility is further reduced when N155H occurs in combination with E92Q and other primary or accessory INI-resistance mutations. N155H has been selected by DTG in RAL-experienced patients but does not reduce DTG susceptibility by itself. N155S/T are rare nonpolymorphic mutations selected in vitro by investigational INIs. N155S/T reduce RAL and EVG susceptibility somewhat less effectively than N155H |
| 157 | E | Q | E157Q is a polymorphic accessory mutation that is weakly selected in patients receiving RAL. It is selected in vitro by EVG. E157Q reduces RAL susceptibility by about 5-fold and EVG susceptibility by about 2-fold. |
| 163 | G | RK | G163R/K are nonpolymorphic mutations in all subtypes except subtype F. They are commonly selected in patients receiving RAL. Their effect on INI susceptibility has not been well studied. |
| 230 | S | N | S230N is a polymorphism that is not associated with reduced INI susceptibility. |
| 230 | S | R | S230R is a nonpolymorphic accessory mutation selected in vitro and in vivo by RAL and in vitro by EVG. It appears to have minimal, if any, effect on INI susceptibility. |
| 263 | R | K | R263K is a nonpolymorphic mutation selected in patients receiving RAL and DTG and in vitro by EVG and DTG. It reduces RAL, DTG, and EVG susceptibility about 2-fold, 2-fold, and 3 to 5-fold, respectively. |