# POSITION AA CATEGORY COMMENT 51 NOT Y Other H51Y is a nonpolymorphic mutation that is selected in vitro by EVG and in vivo by RAL (Hatano et al. 2010; Reuman et al. 2010). It minimally reduces EVG susceptibility (Jones et al. 2007; Shimura et al. 2007). $listMutsIn{51(NOT Y)} is an unusual mutation at this position. 51 Y INIMinor H51Y is a nonpolymorphic mutation that is selected in vitro by EVG and in vivo by RAL (Hatano et al. 2010; Reuman et al. 2010). It minimally reduces EVG susceptibility (Jones et al. 2007; Shimura et al. 2007). 54 I INIMinor V54I is a minimally polymorphic mutation that has been selected in vitro by RAL (Goethals et al. 2010) 54 NOT I Other None 66 A INIMajor T66A is occasionally selected in vivo by RAL usually in combination with other mutations (Charpentier et al. 2008; Hatano et al. 2010). It minimally reduces EVG but not RAL susceptibility (Goethals et al. 2008; Kobayashi et al. 2008). 66 K INIMajor T66K is associated with markedly decreased EVG susceptibility, moderately decreased RAL susceptibility, and possibly decreased 9572 susceptibility(Kobayashi et al. 2008; Seki et al. 2010). 66 I INIMajor T66I is a nonpolymorphic mutation selected by EVG (Shimura et al. 2007; Goethals et al. 2008). T66I decreases EVG susceptibility ~15-fold but does not reduce RAL susceptibility (Shimura et al. 2007; Goethals et al. 2008; Kobayashi et al. 2008; Jones et al. 2009; Goethals et al. 2010). 66 NOT IAK INIMinor T66K is associated with markedly decreased EVG susceptibility, moderately decreased RAL susceptibility, and possibly decreased 9572 susceptibility(Kobayashi et al. 2008; Seki et al. 2010). T66I is a nonpolymorphic mutation selected by EVG (Shimura et al. 2007; Goethals et al. 2008). T66I decreases EVG susceptibility ~15-fold but does not reduce RAL susceptibility (Shimura et al. 2007; Goethals et al. 2008; Kobayashi et al. 2008; Jones et al. 2009; Goethals et al. 2010). T66A is occasionally selected in vivo by RAL usually in combination with other mutations (Charpentier et al. 2008; Hatano et al. 2010). It minimally reduces EVG but not RAL susceptibility (Goethals et al. 2008; Kobayashi et al. 2008). $listMutsIn{66(NOT IAK)} is an unusual mutation at this position. 68 NOT VI Other None 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). 72 I Other V72I is a highly polymorphic mutation selected in vitro by pre-RAL/EVG INIs. It does not decrease susceptibility INI susceptibility (Fransen et al. 2006; Goethals et al. 2008; Low et al. 2009; da Silva et al. 2010). 72 NOT V Other V72I is a highly polymorphic mutation selected in vitro by pre-RAL/EVG INIs. It does not decrease susceptibility INI susceptibility (Fransen et al. 2006; Goethals et al. 2008; Low et al. 2009; da Silva et al. 2010). $listMutsIn{72(NOT IV)} is an unusual mutation at this position. 74 MR INIMinor L74MR is a polymorphic accessory INI-resistance mutation selected by RAL (Cooper et al. 2008; Sichtig et al. 2009; Wittkop et al. 2009). It does not decrease INI susceptibility alone but decreases RAL susceptibility in combination with N155H (Kobayashi et al. 2008; Miller et al. 2008; Jones et al. 2009; Reuman et al. 2010). 74 NOT MR Other None 92 NOT QV INIMinor E92Q is a nonpolymorphic mutation selected by RAL and EVG (Shimura et al. 2007; Goethals et al. 2008; Malet et al. 2008; Jones et al. 2009; Sichtig et al. 2009). It reduces RAL and EVG susceptibility by about 5 and >30-fold, respectively(Shimura et al. 2007; Goethals et al. 2008; Jones et al. 2009; Goethals et al. 2010). E92Q emerged during in vitro passage with 9572, but only minimally reduces 9572 susceptibility (Sato et al. 2009; Sato et al. 2010). E92V has been reported to emerge during in vitro passage with GS-9160 and to reduce RAL and EVG susceptibility 10 and 40-fold, respectively (Jones et al. 2009). $listMutsIn{92(NOT QV)} is an unusual mutation at this position. 92 Q INIMajor E92Q is a nonpolymorphic mutation selected by RAL and EVG (Shimura et al. 2007; Goethals et al. 2008; Malet et al. 2008; Jones et al. 2009; Sichtig et al. 2009). It reduces RAL and EVG susceptibility by about 5 and >30-fold, respectively(Shimura et al. 2007; Goethals et al. 2008; Jones et al. 2009; Goethals et al. 2010). E92Q emerged during in vitro passage with 9572, but only minimally reduces 9572 susceptibility (Sato et al. 2009; Sato et al. 2010). 92 V INIMajor E92V has been reported to emerge during in vitro passage with GS-9160 and to reduce RAL and EVG susceptibility 10 and 40-fold, respectively (Jones et al. 2009) 95 K INIMinor Q95K is a minimally polymorphic accessory INI-resistance mutation selected in vitro by EVG and in vivo by RAL (Shimura et al. 2007; Merck 2009). By itself it has little if any effect on INI susceptibility (Shimura et al. 2007) 95 NOT K Other Q95K is a minimally polymorphic accessory INI-resistance mutation selected in vitro by EVG and in vivo by RAL (Shimura et al. 2007; Merck 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 by RAL often in combination with Y143 mutations (Malet et al. 2008; Miller et al. 2008; Canducci et al. 2009; Fransen et al. 2009a; Reuman et al. 2010). It has no effect on INI susceptibility alone but markedly reduces RAL susceptibility in combination with Y143CR it markedly reduces(Fransen et al. 2009a; Reuman et al. 2010). 97 NOT A Other None 114 NOT Y Other H114Y is a nonpolymorphic accessory resistance mutation selected in vitro by EVG (Goethals et al. 2008). $listMutsIn{114(NOT Y)} is an unusual mutation at this position. 114 Y INIMinor H114Y is a nonpolymorphic accessory resistance mutation selected in vitro by EVG (Goethals et al. 2008). 121 NOT Y INIMinor F121Y is a nonpolymorphic mutation that is selected in vitro by RAL (Rowley 2008) and EVG (Shimura et al. 2007). It reduces susceptibility to RAL and EVG by about 5 and 10-fold, respectively (Jones et al. 2007; Shimura et al. 2007; Kobayashi et al. 2008). It has not been observed in clinical isolates. $listMutsIn{121(NOT Y)} 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 (Shimura et al. 2007). It reduces susceptibility to RAL and EVG by about 5 and 10-fold, respectively (Jones et al. 2007; Shimura et al. 2007; Kobayashi et al. 2008). It has not been observed in clinical isolates. 125 K INIMinor T125K is a nonpolymorphic mutation selected in vitro by L870,810. It has not been selected in vivo with current INIs nor found to decrease their susceptibility (Shimura et al. 2007; Kobayashi et al. 2008; Rowley 2008). 125 NOT K Other None 128 NOT T Other A128T is a nonpolymorphic mutation 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 selected in vitro by EVG but which does not reduce INI susceptibility (Fikkert et al. 2004; Goethals et al. 2008) 138 KA INIMajor E138KA are nonpolymorphic accessory resistance mutations selected in vitro and in vivo by RAL, EVG, and 9572 usually in combination with Q148 mutations(Hazuda et al. 2007; McColl et al. 2007; Sato et al. 2009; Goethals et al. 2010). Alone they do not reduce INI susceptibility but in combination with Q148 mutations they reduce RAL and EVG susceptibility >100-fold and 9572 susceptibility >10-fold (Shimura et al. 2007; Goethals et al. 2008; Jones et al. 2009; Seki et al. 2010). 138 NOT KA INIMinor E138KA are nonpolymorphic accessory resistance mutations selected in vitro and in vivo by RAL, EVG, and 9572 usually in combination with Q148 mutations(Hazuda et al. 2007; McColl et al. 2007; Sato et al. 2009; Goethals et al. 2010). Alone they do not reduce INI susceptibility but in combination with Q148 mutations they reduce RAL and EVG susceptibility >100-fold and 9572 susceptibility >10-fold (Shimura et al. 2007; Goethals et al. 2008; Jones et al. 2009; Seki et al. 2010). $listMutsIn{138(NOT KA)} is an unusual mutation at this position. 140 NOT SAC INIMinor G140S is a nonpolymorphic mutation that usually occurs with Q148HRK in patients receiving RAL (Charpentier et al. 2008; Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010) and EVG (McColl et al. 2007). By itself it does not reduce INI susceptibility(Jones et al. 2009; Quercia et al. 2009; Goethals et al. 2010). However, in combination with Q148HRK, it reduces RAL and EVG susceptibility >100-fold and 9572 ~10-fold. G140AC are less well-studied variants that appear to have effects similar to G140S (Jones et al. 2009; Quercia et al. 2009). $listMutsIn{140(NOT SAC)} is an unusual mutation at this position. 140 SAC INIMajor G140S is a nonpolymorphic mutation that usually occurs with Q148HRK in patients receiving RAL (Charpentier et al. 2008; Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010) and EVG (McColl et al. 2007). By itself it does not reduce INI susceptibility(Jones et al. 2009; Quercia et al. 2009; Goethals et al. 2010). However, in combination with Q148HRK, it reduces RAL and EVG susceptibility >100-fold and 9572 ~10-fold. G140AC are less well-studied variants that appear to have effects similar to G140S (Jones et al. 2009; Quercia et al. 2009). 143 CRH INIMajor Y143CR are nonpolymorphic mutations selected by RAL (Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010). Alone Y143C and Y143R reduce RAL susceptibility by ~5 and 20-fold respectively but with T97A or other accessory mutations, they reduce RAL susceptibility >100-fold (Fransen et al. 2009a; Reuman et al.). Y143 mutations have no effect on EVG or 9572 susceptibility (DeAnda et al. 2010; Seki et al. 2010). Y143H is a less common mutation at this position that may be primarily transitional. 143 NOT CRH INIMinor Y143CR are nonpolymorphic mutations selected by RAL (Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010). Alone Y143C and Y143R reduce RAL susceptibility by ~5 and 20-fold respectively but with T97A or other accessory mutations, they reduce RAL susceptibility >100-fold (Fransen et al. 2009a; Reuman et al.). Y143 mutations have no effect on EVG or 9572 susceptibility (DeAnda et al. 2010; Seki et al. 2010). Y143H is a less common mutation at this position that may be primarily transitional. $listMutsIn{143(NOT CRH)} is an unusual mutation at this position. 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; Seki et al. 2010). $listMutsIn{145(NOT S)} 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; Seki et al. 2010). 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. 147 G INIMajor S147G is a nonpolymorphic mutation selected by EVG (McColl et al. 2007). It reduces EVG susceptibility 5 to 10-fold (Shimura et al. 2007) but has minimal if any effect on RAL susceptibility (Van Baelen et al. 2009). 147 NOT G INIMinor S147G is a nonpolymorphic mutation selected by EVG (McColl et al. 2007). It reduces EVG susceptibility 5 to 10-fold (Shimura et al. 2007) but has minimal if any effect on RAL susceptibility (Van Baelen et al. 2009). $listMutsIn{147(NOT G)} is an unusual mutation at this position. 148 HKR INIMajor Q148HKR are nonpolymorphic mutations selected by RAL and EVG (McColl et al. 2007; Cooper et al. 2008; Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010). By itself Q148H reduces RAL and EVG susceptibility about 5-10 fold and Q148RK reduce RAL and EVG susceptibility >30-100 fold. With G140S, Q148HRK reduce RAL and EVG susceptibility >100-fold. (Kobayashi et al. 2008; Fransen et al. 2009b; Jones et al. 2009; Goethals et al. 2010). (McColl et al. 2007; Fransen et al. 2009a; Jones et al. 2009). Q148HKR alone have minimal effects on 9572 susceptibility but cause >10-fold decreased susceptibility in combination with E138K +/- G140S (Seki et al. 2010). 148 NOT HKR INIMinor Q148HKR are nonpolymorphic mutations selected by RAL and EVG (McColl et al. 2007; Cooper et al. 2008; Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010). By itself Q148H reduces RAL and EVG susceptibility about 5-10 fold and Q148RK reduce RAL and EVG susceptibility >30-100 fold. With G140S, Q148HRK reduce RAL and EVG susceptibility >100-fold. (Kobayashi et al. 2008; Fransen et al. 2009b; Jones et al. 2009; Goethals et al. 2010). (McColl et al. 2007; Fransen et al. 2009a; Jones et al. 2009). Q148HKR alone have minimal effects on 9572 susceptibility but cause >10-fold decreased susceptibility in combination with E138K +/- G140S (Seki et al. 2010). $listMutsIn{148(NOT HKR)} is an unusual mutation at this position. 151 A INIMinor 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 I 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). 151 L INIMinor V151L has been selected in vitro by early investigational INIs but not in vivo with current INIs. It decreases susceptibility to RAL, EVG, and 9572 (Kobayashi et al. 2008; Seki et al. 2010). 151 NOT IAL Other 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). V151L has been selected in vitro by early investigational INIs but not in vivo with current INIs. It decreases susceptibility to RAL, EVG, and 9572 (Kobayashi et al. 2008; Seki et al. 2010). $listMutsIn{151(NOT IAL)} is an unusual mutation at this position. 153 NOT Y Other 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 and 9572 susceptibility (Jones et al. 2007; Kobayashi et al. 2008; Marinello et al. 2008). $listMutsIn{153(NOT Y)} is an unusual mutation at this position. 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 and 9572 susceptibility (Jones et al. 2007; Kobayashi et al. 2008; Marinello et al. 2008). 154 IL Other 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; Low et al. 2009; Miller 2009). 154 NOT IL Other None 155 H INIMajor N155H is a nonpolymorphic mutation selected by RAL and EVG (McColl et al. 2007; Cooper et al. 2008; Malet et al. 2008; Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010). It decreases RAL and EVG susceptibility >20-fold (Kobayashi et al. 2008; Jones et al. 2009; Goethals et al. 2010; Reuman et al. 2010). N155H contributes to 9572 resistance in combination with other INI-resistance mutations (Seki et al. 2010). 155 NOT HS INIMinor N155H is a nonpolymorphic mutation selected by RAL and EVG (McColl et al. 2007; Cooper et al. 2008; Malet et al. 2008; Canducci et al. 2009; Sichtig et al. 2009; Wittkop et al. 2009; Hatano et al. 2010). It decreases RAL and EVG susceptibility >20-fold (Kobayashi et al. 2008; Jones et al. 2009; Goethals et al. 2010; Reuman et al. 2010). N155H contributes to 9572 resistance in combination with other INI-resistance mutations (Seki et al. 2010). N155S is an uncommon nonpolymorphic INI-resistance mutation, selected in vitro by L870,810, that decreases RAL and EVG susceptibility to an extent less than that of N155H (Kobayashi et al. 2008; Jones et al. 2009; Goethals et al. 2010). $listMutsIn{155(NOT HS)} is an unusual mutation at this position. 155 S INIMajor N155S is an uncommon nonpolymorphic INI-resistance mutation, selected in vitro by L870,810, that decreases RAL and EVG susceptibility to an extent less than that of N155H (Kobayashi et al. 2008; Jones et al. 2009; Goethals et al. 2010). 157 NOT Q Other 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 (Goethals et al. 2010; Reuman et al. 2010). $listMutsIn{157(NOT Q)} is an unusual mutation at this position. 157 Q Other 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 (Goethals et al. 2010; Reuman et al. 2010). 163 NOT RK Other None 163 RK INIMinor G163RK are polymorphic accessory INI-resistance mutation that usually occur in combination with N155H in patients receiving RAL (Markowitz et al. 2007; Merck 2009). They do not appear to reduce INI susceptibility (Shimura et al. 2007). 193 E Other G193E emerged in combination with E92Q during in vitro passage with 9572 (Sato et al. 2009). However, it does not decrease 9572 susceptibility. 193 NOT E Other None 201 I Other V201I is a common polymorphism possibly associated with reduced susceptibility to early investigational INIs but not to current INIs (Hombrouck et al. 2008; Low et al. 2009; Miller 2009; da Silva et al. 2010). 201 NOT I Other V201I is a common polymorphism possibly associated with reduced susceptibility to early investigational INIs but not to current INIs (Hombrouck et al. 2008; Low et al. 2009; Miller 2009; da Silva et al. 2010). $listMutsIn{201(NOT I)} is an unusual mutation at this position. 203 M Other I203M is a polymorphic mutation that may occur with increased frequency patients receiving RAL but appears to have no effect on INI susceptibility (Cooper et al. 2008; Malet et al. 2008; da Silva et al. 2010). 203 NOT M Other None 206 NOT S Other T206S is a common polymorphism that may occur with increased frequency patients receiving RAL but which does not affect INI susceptibility (Low et al. 2009; Miller 2009; da Silva et al. 2010). $listMutsIn{206(NOT S)} is an unusual mutation at this position. 206 S Other T206S is a common polymorphism that may occur with increased frequency patients receiving RAL but which does not affect INI susceptibility (Low et al. 2009; Miller 2009; da Silva et al. 2010). 230 NOT NR Other None 230 N Other S230N 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 (Low et al. 2009). S230N is polymorphic. 230 R INIMinor S230R 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 (Low et al. 2009). S230R is not polymorphic. 263 K INIMinor R263K is a nonpolymorphic mutation selected in vitro by EVG and shown to reduce its susceptibility by ~5 fold (Jones et al. 2007) 263 NOT K Other R263K is a nonpolymorphic mutation selected in vitro by EVG and shown to reduce its susceptibility by ~5 fold (Jones et al. 2007). $listMutsIn{263(NOT K)} is an unusual mutation at this position.