# POSITION AA CATEGORY COMMENT 66 AK INIMajor T66AK are nonpolymorphic mutations selected in vivo by EVG (Jones et al. 2007; McColl et al. 2007; Shimura et al. 2007). T66I decreases EVG susceptibility 15-fold but does not reduce RAL susceptibility (Shimura et al. 2007; Rowley 2008; Jones et al. 2009). T66A has been selected in vitro with RAL in combination with Y143CR and Q95K in one experiment (Witmer et al. 2007) and in vivo with E92Q in one patient (Charpentier et al. 2008). T66K appears to be associated with decreased RAL -- as well as EVG -- susceptibility (Kobayashi et al. 2008). 66 I INIMajor T66I is a nonpolymorphic mutation selected in vivo by EVG (Jones et al. 2007; McColl et al. 2007; Shimura et al. 2007). T66I decreases EVG susceptibility 15-fold but does not reduce RAL susceptibility (Shimura et al. 2007; Rowley 2008; Jones et al. 2009). 66 NOT IAK INIMajor T66IAK are nonpolymorphic mutations selected in vivo by EVG (Jones et al. 2007; McColl et al. 2007; Shimura et al. 2007). T66I decreases EVG susceptibility 15-fold but does not reduce RAL susceptibility (Shimura et al. 2007; Rowley 2008; Jones et al. 2009). T66A has been selected in vitro with RAL in combination with Y143CR and Q95K in one experiment (Witmer et al. 2007) and in vivo with E92Q in one patient (Charpentier et al. 2008). T66K appears to be associated with decreased RAL -- as well as EVG -- susceptibility (Kobayashi et al. 2008). $listMutsIn{66(NOT IAK)} is an unusual mutation at this position. 92 QV INIMajor E92Q is a nonpolymorphic mutation that decreases RAL and EVG susceptibility about 5 and 30-fold, respectively (Jones et al. 2007; McColl et al. 2007; Shimura et al. 2007; Goethals et al. 2008; Jones et al. 2009). In patients receiving RAL, E92Q usually occurs in combination with N155H (Malet et al. 2008; Miller et al. 2008; Sichtig et al. 2009). E92V has been reported to emerge during INI selection pressure in vitro and has been associated with reductions in RAL and EVG susceptibility similar to that of E92Q (Jones et al. 2009). 92 NOT QV INIMajor E92Q is a nonpolymorphic mutation that decreases RAL and EVG susceptibility about 5 and 30-fold, respectively (Jones et al. 2007; McColl et al. 2007; Shimura et al. 2007; Goethals et al. 2008; Jones et al. 2009). In patients receiving RAL, E92Q usually occurs in combination with N155H (Malet et al. 2008; Miller et al. 2008; Sichtig et al. 2009). E92V has been reported to emerge during INI selection pressure in vitro and has been associated with reductions in RAL and EVG susceptibility similar to that of E92Q (Jones et al. 2009). $listMutsIn{92(NOT QV)} is an unusual mutation at this position. 121 Y INIMajor F121Y is a nonpolymorphic mutation that is selected in vitro by RAL (Rowley 2008) and EVG (Jones et al. 2007; Shimura et al. 2007). It reduces susceptibility to RAL and EVG by about 5 and 10-fold, respectively (Jones et al. 2007; Ren et al. 2007; Shimura et al. 2007; Rowley 2008). It has not been observed in clinical isolates 121 NOT Y INIMajor F121Y is a nonpolymorphic mutation that is selected in vitro by RAL (Rowley 2008) and EVG (Jones et al. 2007; Shimura et al. 2007). It reduces susceptibility to RAL and EVG by about 5 and 10-fold, respectively (Jones et al. 2007; Ren et al. 2007; Shimura et al. 2007; Rowley 2008). It has not been observed in clinical isolates. $listMutsIn{121(NOT Y)} is an unusual mutation at this position. 140 SAC INIMajor G140S is a nonpolymorphic mutation that usually occurs with Q148HRK in patients receiving RAL (Cooper et al. 2007; Charpentier et al. 2008; Miller et al. 2008; Canducci et al. 2009; Sichtig et al. 2009) or less commonly EVG (McColl et al. 2007). By itself it causes minimum reductions in INI susceptibility(McColl et al. 2007; Goodman et al. 2008; Jones et al. 2009; Quercia et al. 2009). However, G140S + Q148H reduces RAL and EVG susceptibility >1,000-fold. G140A/C are less well-studied variants at this position (McColl et al. 2007; Goodman et al. 2008; Jones et al. 2009; Quercia et al. 2009). 140 NOT SAC INIMajor G140S is a nonpolymorphic mutation that usually occurs with Q148HRK in patients receiving RAL (Cooper et al. 2007; Charpentier et al. 2008; Miller et al. 2008; Canducci et al. 2009; Sichtig et al. 2009) or less commonly EVG (McColl et al. 2007). By itself it causes minimum reductions in INI susceptibility(McColl et al. 2007; Goodman et al. 2008; Jones et al. 2009; Quercia et al. 2009). However, G140S + Q148H reduces RAL and EVG susceptibility >1,000-fold. G140A/C are less well-studied variants at this position (McColl et al. 2007; Goodman et al. 2008; Jones et al. 2009; Quercia et al. 2009). $listMutsIn{140(NOT SAC)} is an unusual mutation at this position. 143 CR INIMajor Y143CR are nonpolymorphic mutations selected in vitro (Witmer et al. 2007) and in vivo by RAL (Cooper et al. 2007; Hazuda et al. 2007; Canducci et al. 2009; Fransen et al. 2009; Sichtig et al. 2009). Y143R reduces RAL susceptibility by >100-fold (Fransen et al. 2009). Y143C reduces RAL susceptibility by about 10-fold (Fransen et al. 2009). These mutations appear to have little, if any, effect on EVG susceptibility (Jegede et al. 2008). 143 H INIMajor Y143CRH are nonpolymorphic mutations selected in vitro (Witmer et al. 2007) and in vivo by RAL (Cooper et al. 2007; Hazuda et al. 2007; Canducci et al. 2009; Fransen et al. 2009; Sichtig et al. 2009). Y143R reduces RAL susceptibility by >100-fold (Fransen et al. 2009). Y143C reduces RAL susceptibility by about 10-fold (Fransen et al. 2009). These mutations appear to have little, if any, effect on EVG susceptibility (Jegede et al. 2008). Y143H susceptibility data are not available. 143 NOT CRH INIMajor Y143CRH are nonpolymorphic mutations selected in vitro (Witmer et al. 2007) and in vivo by RAL (Cooper et al. 2007; Hazuda et al. 2007; Canducci et al. 2009; Fransen et al. 2009; Sichtig et al. 2009). Y143R reduces RAL susceptibility by >100-fold (Fransen et al. 2009). Y143C reduces RAL susceptibility by about 10-fold (Fransen et al. 2009). These mutations appear to have little, if any, effect on EVG susceptibility (Jegede et al. 2008). Y143H susceptibility data are not available. $listMutsIn{143(NOT CRH)} is an unusual mutation at this position. 147 G INIMajor S147G is a nonpolymorphic mutation selected in vivo by EVG (McColl et al. 2007). It reduces EVG susceptibility 5 to 10-fold (Jones et al. 2007; Shimura et al. 2007; Goodman et al. 2008) but has minimal if any effect on RAL susceptibility (McColl et al. 2007). 147 NOT G INIMajor S147G is a nonpolymorphic mutation selected in vivo by EVG (McColl et al. 2007). It reduces EVG susceptibility 5 to 10-fold (Jones et al. 2007; Shimura et al. 2007; Goodman et al. 2008) but has minimal if any effect on RAL susceptibility (McColl et al. 2007). $listMutsIn{147(NOT G)} is an unusual mutation at this position. 148 HKR INIMajor Q148HKR are nonpolymorphic mutations selected in vitro and in vivo by RAL and EVG (Cooper et al. 2007; Hazuda et al. 2007; McColl et al. 2007; Fransen et al. 2009). By themselves Q148HKR reduce RAL susceptibility by 20 to 30-fold or higher (McColl et al. 2007; Goodman et al. 2008) and reduce EVG susceptibility by about 5-fold (Q148H), 50-fold (Q148K), and >100-fold (Q148R) (Goodman et al. 2008). With G140S, Q148H is associated with >1,000-fold decreased RAL and EVG susceptibility (McColl et al. 2007; Fransen et al. 2009; Jones et al. 2009). 148 NOT HKR INIMajor Q148HKR are nonpolymorphic mutations selected in vitro and in vivo by RAL and EVG (Cooper et al. 2007; Hazuda et al. 2007; McColl et al. 2007; Fransen et al. 2009). By themselves Q148HKR reduce RAL susceptibility by 20 to 30-fold or higher (McColl et al. 2007; Goodman et al. 2008) and reduce EVG susceptibility by about 5-fold (Q148H), 50-fold (Q148K), and >100-fold (Q148R) (Goodman et al. 2008). With G140S, Q148H is associated with >1,000-fold decreased RAL and EVG susceptibility (McColl et al. 2007; Fransen et al. 2009; Jones et al. 2009). $listMutsIn{148(NOT HKR)} is an unusual mutation at this position. 155 H INIMajor N155H is a nonpolymorphic mutation selected in vivo by RAL and EVG (Cooper et al. 2007; Hazuda et al. 2007; McColl et al. 2007; Malet et al. 2008; Fransen et al. 2009; Sichtig et al. 2009). It decreases susceptibility to these INIs by about 20 and 30-fold, respectively (McColl et al. 2007; Goodman et al. 2008; Fransen et al. 2009; Jones et al. 2009). N155S is an uncommon nonpolymorphic INI-resistance mutation, selected in vitro by L870,810, that appears to have an effect on RAL and EVG susceptibility similar to that of N155H (Jones et al. 2009). 155 S INIMajor N155S is an uncommon nonpolymorphic INI-resistance mutation, selected in vitro by L870,810, that appears decrease RAL and EVG susceptibility to an extent less than that of N155H (Kobayashi et al. 2008; Jones et al. 2009). 155 NOT HS INIMajor N155H is a nonpolymorphic mutation selected in vivo by RAL and EVG (Cooper et al. 2007; Hazuda et al. 2007; McColl et al. 2007; Malet et al. 2008; Fransen et al. 2009; Sichtig et al. 2009). It decreases susceptibility to these INIs by about 20 and 30-fold, respectively (McColl et al. 2007; Goodman et al. 2008; Fransen et al. 2009; Jones et al. 2009). N155S is an uncommon nonpolymorphic INI-resistance mutation, selected in vitro by L870,810, that appears to have an effect on RAL and EVG susceptibility similar to that of N155H (Jones et al. 2009). $listMutsIn{155(NOT I)} is an unusual mutation at this position. 51 Y INIMinor H51Y is a nonpolymorphic mutation that has been selected in vitro by EVG and shown to minimally reduce EVG susceptibility (Jones et al. 2007; Shimura et al. 2007) 51 NOT Y INIMinor H51Y is a nonpolymorphic mutation that has been selected in vitro by EVG and shown to minimally reduce EVG susceptibility (Jones et al. 2007; Shimura et al. 2007). $listMutsIn{51(NOT Y)} is an unusual mutation at this position. 68 VI INIMinor L68VI are polymorphic accessory INI-resistance mutations selected in vivo by EVG that contribute to decreased RAL and EVG susceptibility in combination with E92Q (Goodman et al. 2008). 68 NOT VI Other None 72 I Other V72I is a highly polymorphic mutation that has been selected in vitro by pre-RAL/EVG INIs. It does not appear to be selected by or to decrease susceptibility to RAL or EVG (Fransen et al. 2006; Goethals et al. 2008; Rhee et al. 2008; Miller 2009). 72 NOT I Other V72I is a highly polymorphic mutation that has been selected in vitro by pre-RAL/EVG INIs. It does not appear to be selected by or to decrease susceptibility to RAL or EVG (Fransen et al. 2006; Goethals et al. 2008; Rhee et al. 2008; Miller 2009). $listMutsIn{72(NOT I)} is an unusual mutation at this position. 74 M INIMinor L74M is a polymorphic accessory INI-resistance mutation selected by RAL (Hazuda et al. 2007) that decreases RAL susceptibility in combination with N155H (Miller et al. 2008). 74 NOT M Other None 95 K INIMinor Q95K is a nonpolymorphic accessory INI-resistance mutation selected in vivo and in vitro by RAL and EVG (Shimura et al. 2007; Jegede et al. 2008; Steigbigel et al. 2009). By itself it has little if any effect on INI susceptibility (Shimura et al. 2007) 95 NOT K INIMinor Q95K is a nonpolymorphic accessory INI-resistance mutation selected in vivo and in vitro by RAL and EVG (Shimura et al. 2007; Jegede et al. 2008; Steigbigel et al. 2009). By itself it has little if any effect on INI susceptibility (Shimura et al. 2007). $listMutsIn{95(NOT K)} is an unusual mutation at this position. 97 A INIMinor T97A is a polymorphic accessory INI-resistance mutation selected in vivo by RAL often in combination with Y143 mutations (Malet et al. 2008; Miller et al. 2008; Canducci et al. 2009; Fransen et al. 2009). It decreases RAL susceptibility in combination with N155H (Hazuda et al. 2007; Miller et al. 2008; Fransen et al. 2009) 97 NOT A Other None 114 Y INIMinor H114Y is a nonpolymorphic accessory resistance mutation reported to be selected in vitro by EVG (Goethals et al. 2008). 114 NOT Y INIMinor H114Y is a nonpolymorphic accessory resistance mutation reported to be selected in vitro by EVG (Goethals et al. 2008). $listMutsIn{114(NOT Y)} is an unusual mutation at this position. 125 K INIMinor T125K is a nonpolymorphic accessory INI-resistance mutation which has been selected in vitro by L870,810 which acts synergistically with F121Y to decrease RAL and EVG susceptibility (Shimura et al. 2007; Kobayashi et al. 2008; Rowley 2008). 125 NOT K Other None 128 NOT T INIMinor A128T is a nonpolymorphic mutation that has been selected in vitro by EVG but which does not reduce INI susceptibility (Fikkert et al. 2004; Goethals et al. 2008). $listMutsIn{128(NOT T)} is an unusual mutation at this position. 128 T INIMinor A128T is a nonpolymorphic mutation that has been selected in vitro by EVG but which does not reduce INI susceptibility (Fikkert et al. 2004; Goethals et al. 2008) 138 KA INIMinor E138KA are nonpolymorphic accessory INI-resistance mutations selected in patients receiving RAL and EVG often in combination with mutations at position 48 (Hazuda et al. 2007; McColl et al. 2007). By itself they do not reduce RAL or EVG susceptibility (McColl et al. 2007; Shimura et al. 2007; Goethals et al. 2008; Goodman et al. 2008; Jones et al. 2009). 138 NOT KA INIMinor E138KA are nonpolymorphic accessory INI-resistance mutations selected in patients receiving RAL and EVG often in combination with mutations at position 48 (Hazuda et al. 2007; McColl et al. 2007). By itself they do not reduce RAL or EVG susceptibility (McColl et al. 2007; Shimura et al. 2007; Goethals et al. 2008; Goodman et al. 2008; Jones et al. 2009). $listMutsIn{138(NOT KA)} is an unusual mutation at this position. 145 S INIMajor P145S is a nonpolymorphic mutation that has been selected in vitro by EVG and causes high-level resistance to EVG (Garvey et al. 2008; Kobayashi et al. 2008). 145 NOT S INIMinor P145S is a nonpolymorphic mutation that has been selected in vitro by EVG and causes high-level resistance to EVG (Garvey et al. 2008; Kobayashi et al. 2008). $listMutsIn{145(NOT S)} is an unusual mutation at this position. 146 NOT P INIMinor Q146P is a nonpolymorphic mutation that has been selected in vitro by EVG and shown to reduce EVG susceptibility about 10-fold (Shimura et al. 2007). Its effect on RAL susceptibility is not known. $listMutsIn{146(NOT P)} is an unusual mutation at this position. 146 P INIMajor Q146P is a nonpolymorphic mutation that has been selected in vitro by EVG and shown to reduce EVG susceptibility about 10-fold (Shimura et al. 2007). Its effect on RAL susceptibility is not known. 153 Y INIMinor S153Y is a nonpolymorphic accessory mutation that has been selected in vitro by EVG usually with T66I (Jones et al. 2007; Shimura et al. 2007). By itself it minimally decreases EVG susceptibility (Jones et al. 2007; Kobayashi et al. 2008; Marinello et al. 2008). 153 NOT Y INIMinor S153Y is a nonpolymorphic accessory mutation that has been selected in vitro by EVG usually with T66I (Jones et al. 2007; Shimura et al. 2007). By itself it minimally decreases EVG susceptibility (Jones et al. 2007; Kobayashi et al. 2008; Marinello et al. 2008). $listMutsIn{153(NOT Y)} is an unusual mutation at this position. 157 Q INIMinor E157Q is a minimally polymorphic mutation that is selected in vitro by EVG (Jones et al. 2007; Shimura et al. 2007) and rarely in vivo by RAL (Malet et al. 2008). It appears to have minimal if any effect on INI susceptibility. 157 NOT Q INIMinor E157Q is a minimally polymorphic mutation that is selected in vitro by EVG (Jones et al. 2007; Shimura et al. 2007) and rarely in vivo by RAL (Malet et al. 2008). It appears to have minimal if any effect on INI susceptibility. $listMutsIn{157(NOT Q)} is an unusual mutation at this position. 163 RK INIMinor G163RK are polymorphic accessory INI-resistance mutation that usually occur in combination with N155H in patients receiving RAL (Hazuda et al. 2007; Markowitz et al. 2007; Sichtig et al. 2009). They do not appear to reduce INI susceptibility (Shimura et al. 2007). 163 NOT RK Other None 263 K INIMinor R263K is a nonpolymorphic mutation that has been selected in vitro by EVG and shown to reduce its susceptibility by about 5 fold (Jones et al. 2007) 263 NOT K INIMinor R263K is a nonpolymorphic mutation that has been selected in vitro by EVG and shown to reduce its susceptibility by about 5 fold (Jones et al. 2007). $listMutsIn{263(NOT K)} is an unusual mutation at this position. 151 IA INIMinor V151I is a polymorphic mutation which has been selected in vitro by multiple INIs but which has no effect on RAL or EVG susceptibility (Hazuda et al. 2004; Markowitz et al. 2007; McColl et al. 2007; Rowley 2008; Low et al. 2009). V151A has been reported to emerge during INI-selection pressure in vitro and has been associated with ~5-fold reduced susceptibility to RAL and EVG (Jones et al. 2009). 151 NOT IA INIMinor V151I is a polymorphic mutation which has been selected in vitro by multiple INIs but which has no effect on RAL or EVG susceptibility (Hazuda et al. 2004; Markowitz et al. 2007; McColl et al. 2007; Rowley 2008; Low et al. 2009). V151A has been reported to emerge during INI-selection pressure in vitro and has been associated with ~5-fold reduced susceptibility to RAL and EVG (Jones et al. 2009). $listMutsIn{151(NOT IA)} is an unusual mutation at this position. 154 IL INIMinor M154IL are polymorphic mutations selected in vitro by pre-RAL/EVG INIs (Hazuda et al. 2000; Hazuda et al. 2004). They do not appear to be selected by nor decrease susceptibility to RAL or EVG (Kobayashi et al. 2008; Rowley 2008; Low et al. 2009; Miller 2009). 154 NOT IL Other None 201 I Other V201I is a common polymorphism that was reported to possibly be associated with reduced susceptibility to the early investigational INIs. However, it does not appear to be selected by or reduce susceptibility to current INIs (Hombrouck et al. 2008; Low et al. 2009; Miller 2009). 201 NOT I Other V201I is a common polymorphism that was reported to possibly be associated with reduced susceptibility to the early investigational INIs. However, it does not appear to be selected by or reduce susceptibility to current INIs (Hombrouck et al. 2008; Low et al. 2009; Miller 2009). $listMutsIn{201(NOT I)} is an unusual mutation at this position. 203 M INIMinor I203M is a polymorphic mutation that occasionally is selected in patients receiving RAL (Cooper et al. 2007; Malet et al. 2008). It has not been reported to reduce RAL or EVG susceptibility. 203 NOT M Other None 206 S Other T206S is a common polymorphism that may occur somewhat more frequently under INI selection pressure but which does not appear to affect INI susceptibility (Low et al. 2009; Miller 2009). 206 NOT S Other T206S is a common polymorphism that may occur somewhat more frequently under INI selection pressure but which does not appear to affect INI susceptibility (Low et al. 2009; Miller 2009). $listMutsIn{206(NOT S)} is an unusual mutation at this position. 230 NR INIMinor S230N/R were reported to possibly be associated with reduced susceptibility to the early investigational INIs. However, they do not appear to be selected by or reduce susceptibility to current INIs (Low et al. 2009; Miller 2009). S230N is polymorphic; S230R is not. 230 NOT NR Other None