# POSITION AA CATEGORY SCORE COMMENT 41 L NRTI Yes M41L usually occurs with T215Y. Together these mutations confer intermediate-to-high level resistance to AZT and d4T and a lower level of resistance to ddI, ABC, and TDF. 41 NOT L NRTI M41L usually occurs with T215Y. Together these mutations confer intermediate-to-high level resistance to AZT and d4T and a lower level of resistance to ddI, ABC, and TDF. $listMutsIn{41(NOT L)} is a highly unusual mutation at this position. 44 AD NRTI Yes E44A/D occur in patients receiving multiple NRTIs. E44D causes low-level resistance to 3TC and probably to each of the other NRTIs when present with V118I or one or more TAMs. 44 NOT AD Other None 62 V NRTI Yes A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known. 62 NOT V Other A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known. $listMutsIn{62(NOT V)} is a highly unusual mutation at this position. 65 N NRTI Yes K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF, and low-level resistance to d4T. K65R causes AZT hypersusceptibility. K65N is an extremely rare mutation that may have a similar effect. 65 R NRTI Yes K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF, and low-level resistance to d4T. K65R causes AZT hypersusceptibility. 65 NOT NR NRTI K65R/N are known NRTI-resistance mutations. $listMutsIn{65(NOT NR)} is a highly unusual mutation at this position. 67 EG NRTI Yes D67N contributes some degree of resistance to each of the NRTIs except 3TC and FTC. It usually occurs with mutations at positions 70 or 215. D67E/G occur in heavily treated patients but their precise effect on NRTI susceptibility is not known. 67 N NRTI Yes D67N contributes some degree of resistance to each of the NRTIs except 3TC and FTC. It usually occurs with mutations at positions 70 or 215. 67 d NRTI Yes Amino acid deletions (d) in this region occur uncommonly. They occur in combination with other NRTI mutations and contribute decreased susceptibility to each of the NRTIs. 67 NOT EGNd NRTI D67N contributes some degree of resistance to each of the NRTIs except 3TC and FTC. It usually occurs with mutations at positions 70 or 215. D67E/G occur in heavily treated patients but their precise effect on NRTI susceptibility is not known. $listMutsIn{67(NOT EGNd)} is a highly unusual mutation at this position. 69 NSAI NRTI Yes T69N/S/A/I are NRTI-selected mutations but their effect on NRTI susceptibility is not known. 69 D NRTI Yes T69D, a mutation originally identified for its role in causing ddC reistance, is associated with decreased susceptibility to ddI and d4T. 69 G NRTI Yes T69G occurs in isolates with a deletion at position 67 but its effect on NRTI susceptibility is not known. 69 i NRTI Yes Amino acid insertions (i) at this position occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to each of the NRTIs. Most susceptibility data are available for double amino acid insertions. However, insertions of 1 or >2 amino acids also occur. 69 NOT ADGINSi NRTI T69D/N/S/G/A/I are NRTI-selected mutations. $listMutsIn{69(NOT ADGINSi)} is a highly unusual mutation at this position. 70 EG NRTI Yes K70E/G reduces TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility. 70 R NRTI Yes K70R causes low-level AZT, d4T, and possibly TDF resistance. 70 NOT EGR NRTI K70R causes low-level AZT, d4T, and possibly TDF resistance. K70E/G reduces TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility. $listMutsIn{70(NOT EGR)} is an unusual mutation at this position. 74 I NRTI Yes L74V reduces susceptibility to ddI and ABC susceptibility and increases susceptibility AZT and TDF. 74 V NRTI Yes L74V reduces susceptibility to ddI and ABC susceptibility and increases susceptibility AZT and TDF. L74I appears to have a similar effect but may not increase AZT and TDF susceptibility. 74 NOT IV NRTI L74V reduces susceptibility to ddI and ABC susceptibility and increases susceptibility AZT and TDF. L74I appears to have a similar effect but may not increase AZT and TDF susceptibility. $listMutsIn{74(NOT IV)} is a highly unusual mutation at this position. 75 I NRTI Yes V75I increases multinucleoside resistance caused by Q151M when present with F77L and F116Y; its effect in the absence of Q151M is not known. 75 TMAS NRTI Yes V75T/M/A/S reduce d4T and possibly ddI susceptibility. 75 L NRTI No V75L does not appear to be associated with reduced NRTI susceptibility. 75 NOT AIMSTL NRTI V75M/T/A/S/I are NRTI-selected mutations. $listMutsIn{75(NOT AIMSTL)} is a highly unusual mutation at this position. 77 L NRTI Yes F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y; its effect in the absence of Q151M is not known. 77 NOT L NRTI F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y. $listMutsIn{77(NOT L)} is a highly unusual mutation at this position 90 I NNRTI No V90I is a common polymorphism that was weakly associated with decreased ETR response in the DUET studies. However, it has minimal if any effect on NNRTI susceptibility. 90 NOT I Other None 98 G NNRTI Yes A98G reduces NVP susceptibility by 2 to 3-fold. It is selected by NRTIs and NNRTIs. It was associated with a decreased ETR response in the DUET studies but it has little if any effect on ETR susceptibility. 98 S Other Yes A98S is a common polymorphism that does not reduce NNRTI susceptibility. 98 NOT GS Other None 100 I NNRTI Yes L100I usually occurs in combination with K103N. By itself it causes intermediate resistance to NVP, DLV, and EFV, and 2 to 4-fold decreased ETR susceptibility. In combination with K103N it causes high-level resistance to NVP, DLV, and EFV and 10 to 20-fold decreased ETR susceptibility. L100I increases susceptibility to AZT and TDF. 100 NOT I NNRTI L100I usually occurs in combination with K103N. By itself it causes intermediate resistance to NVP, DLV, and EFV, and 2 to 4-fold decreased ETR susceptibility. In combination with K103N it causes high-level resistance to NVP, DLV, and EFV and 10 to 20-fold decreased ETR susceptibility. $listMutsIn{100(NOT I)} is a highly unusual mutation at this position. 101 E NNRTI Yes K101E causes intermediate resistance to NVP and DLV and low-level resistance to EFV and ETR. 101 HN NNRTI Yes K101H/N are rare NNRTI-associated mutations with uncertain phenotypic and clinical effects. K101H was weakly associated with a decreased ETR response in the DUET studies. 101 P NNRTI Yes K101P nearly always occurs with K103N and in this setting causes high-level resistance to NVP, DLV, and EFV. By itself K101P reduces ETR susceptibility 6-fold. 101 Q NNRTI Yes K101Q is weakly associated with NNRTI therapy and minimally reduces susceptibility to each of the NNRTIs. 101 R Other No K101R is an uncommon polymorphism that has not been associated with decreased NNRTI susceptibility. 101 NOT EHNPQR NNRTI K101E/P/N/H/Q are NNRTI-selected mutations. $listMutsIn{101(NOT EHNPQR)} is a highly unusual mutation at this position. 103 EQ NNRTI No K103E/Q are rare mutations that have not been associated with resistance to the current NNRTIs. 103 TH NNRTI Yes K103T/H are rare mutations that appear to be associated with intermediate/high-level resistance to NVP, DLV, and EFV. 103 N NNRTI Yes K103N causes high-level resistance to NVP, DLV, and EFV. By itself it has no effect on ETR susceptibility. However, it has a synergistic effect with L100I and possibly K101P on ETR susceptibility. 103 R NNRTI Yes K103R occurs in about 1%-2% of untreated persons and by itself has no effect on NNRTI susceptibility. However, the combination of K103R + V179D, reduces NVP, DLV, and EFV susceptibility by about 15-fold. 103 S NNRTI Yes K103S causes high-level resistance to NVP and intermediate/high-level resistance to DLV and EFV. 103 NOT EHNQRST NNRTI K103N/S/T/H are NNRTI-resistance mutations. K103R/E/Q are variants that usually do not cause NNRTI resistance. $listMutsIn{103(NOT EHNQRST)} is a highly unusual mutation at this position. 106 A NNRTI Yes V106A causes high-level resistance to NVP and DLV, and low/intermediate resistance to EFV. Its effect on ETR, if any, appears to be minimal. 106 I NNRTI No V106I is a common polymorphism that was associated with decreased ETR response in the DUE study. However, it does not decrease NNRTI susceptibility. 106 L NNRTI No V106L is a rare polymorphism that does not appear to be associated with NNRTI resistance. 106 M NNRTI Yes V106M causes high-level resistance to NVP, EFV, and DLV but does not appear to decrease ETR susceptibility except as a marker of past NNRTI therapy. 106 NOT AIML NNRTI V106A/M are NNRTI-resistance mutations. V106I/L are polymorphisms that do not appear to cause NNRTI resistance. $listMutsIn{106(NOT AIML)} is a highly unusual mutation at this position. 108 I NNRTI Yes V108I causes low-level reductions in susceptibility to each of the NNRTIs except ETR. It occasionally occurs in the absence of NNRTI therapy. 108 NOT I NNRTI V108I causes low-level reductions in susceptibility to each of the NNRTIs except ETR. It occasionally occurs in the absence of NNRTI therapy. $listMutsIn{108(NOT I)} is a highly unusual mutation at this position. 115 F NRTI Yes Y115F causes intermediate resistance to ABC and low-level resistance to TDF. 115 NOT F NRTI Y115F causes intermediate resistance to ABC and low-level resistance to TDF. $listMutsIn{115(NOT F)} is a highly unusual mutation at this position. 116 Y NRTI Yes F116Y increases multinucleoside resistance caused by Q151M when present with F77L or V75I; its effect in the absence of Q151M is not known. 116 NOT Y NRTI F116Y increases multinucleoside resistance caused by Q151M when present with F77L or V75I; its effect in the absence of Q151M is not known. $listMutsIn{116(NOT Y)} is a highly unusual mutation at this position. 118 I NRTI Yes V118I occurs in ~2% of untreated persons and with increased frequency in persons receiving multiple NRTIs. It causes low-level resistance to 3TC and possibly to other NRTIs when present with E44A/D and/or one or more TAMs. 118 NOT I Other $listMutsIn{V118(NOT I)} is a highly unusual mutation at this position. 138 A NNRTI Yes E138A is a polymorphism that has been recently added to the list of mutations associated with decreased ETR response in the DUET studies. 138 G NNRTI Yes E138G is a rare mutation that has been reported to emerge in patients with ETR failure. It may contribute to decreased ETR susceptibility in combination with other mutations. 138 K NNRTI Yes E138K is selected in vitro by ETR and reduces its susceptibility by about 5-fold. E138K reduces to susceptibility other NNRTIs by about 2 to 5-fold. 138 Q NNRTI Yes E138Q is weakly associated with NNRTI therapy. It may contribute to decreased NNRTI susceptibility in certain genetic contexts. 138 NOT AGKQ NNRTI E138AGKQ are weakly assocated with decreased ETR suscepitibility. $listMutsIn{138(NOT AGKQ)} is an unusual mutation at this position. 151 L NRTI Yes By itself, Q151M causes intermediate-to-high level resistance to AZT, ddI, d4T, and ABC; and low-level resistance to TDF. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC; intermediate resistance to TDF, and low-level resistance to 3TC and FTC. Q151L is a rarely observed transitional mutation that may precede the emergence of the Q151M. 151 M NRTI Yes By itself, Q151M causes intermediate-to-high level resistance to AZT, ddI, d4T, and ABC; and low-level resistance to TDF. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC; intermediate resistance to TDF, and low-level resistance to 3TC and FTC. 151 NOT LM NRTI By itself, Q151M causes intermediate-to-high level resistance to AZT, ddI, d4T, and ABC; and low-level resistance to TDF. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC; intermediate resistance to TDF, and low-level resistance to 3TC and FTC. $listMutsIn{151(NOT LM)} is a highly unusual mutation at this position. 179 DE NNRTI Yes V179D/E cause low-level reductions in susceptibility to NVP, EFV, and DLV. V179D occurs in about 1% of untreated persons and reduces the susceptibility of each NNRTI by about 2-fold. The combination of K103R + V179D reduces the susceptibility of NVP, DLV, and EFV by about 15-fold; the combination's effect on ETR is not known. V179D was associated with a decreased response to ETR in the DUET studies. 179 F NNRTI Yes V179F nearly always occurs in combination with Y181C. By itself, V179F has no effect on ETR susceptibility but in combination with Y181C, it reduces ETR susceptibility >100-fold and causes low-level EFV resistance. It is selected in vivo by ETR. 179 I Other Yes V179I is a common polymorphism which occurs more commonly in NNRTI-treated isolates. However, it does not reduce NNRTI susceptibility. 179 T NNRTI Yes V179T is a rare mutation that was weakly associated with a decreased response to ETR in the DUET studies. It has no apparent effect on NNRTI susceptibility 179 NOT DEFIT NNRTI $listMutsIn{V179(NOT DEFIT)} is an unusual mutation at this position. 181 CIV NNRTI Yes Y181C/I/V cause high-level resistance to NVP and DLV and low-level resistance to EFV. Y181C/I/V reduces ETR susceptibility by 5 to 15-fold and provide the mutational foundation for the development of higher levels of ETR resistance. Y181C increases susceptibility to AZT and TDF. 181 S NNRTI Yes Y181C/I/V cause high-level resistance to NVP and DLV and low-level resistance to EFV. Y181C/I/V reduces ETR susceptibility by 5 to 15-fold and provide the mutational foundation for the development of higher levels of ETR resistance. Y181S is a rare NNRTI-selected mutation that causes intermediate-high resistance to NVP and DLV. Few data are available for EFV and ETR. 181 NOT CISV NNRTI Y181C/I/V cause high-level resistance to NVP and DLV and low-level resistance to EFV. Y181C/I/V reduces ETR susceptibility by 5 to 15-fold and provide the mutational foundation for the development of higher levels of ETR resistance. $listMutsIn{181(NOT CISV)} is a highly unusual mutation at this position. 184 VI NRTI Yes M184V/I cause high-level in vitro resistance to 3TC and FTC and low-level in vitro resistance to ddI and ABC. M184V/I increase susceptibility to AZT, TDF, and d4T. 184 NOT IV M184V/I cause high-level in vitro resistance to 3TC and FTC and low-level in vitro resistance to ddI and ABC. M184V/I increase susceptibility to AZT, TDF, and d4T. $listMutsIn{184(NOT IV)} is a highly unusual mutation at this position. 188 C NNRTI Yes Y188C causes high-level resistance to NVP and low-level resistance to EFV and DLV; its effect on ETR is not known. 188 H NNRTI Yes Y188H causes intermediate resistance to NVP, EFV, and DLV and has been selected in vitro by ETR. 188 L NNRTI Yes Y188L causes high-level resistance to NVP and EFV, intermediate resistance to DLV, and potentially low-level resistance to ETR. 188 F NNRTI No Y188F is a rare mutation at this position of uncertain significance. It is often an artifact of the two-base pair change required for the emergence of Y188L. 188 NOT CHLF Y188L/H/C are NNRTI-resistance mutations. $listMutsIn{188(NOT CHLF)} is a highly unusual mutation at this position. 190 A NNRTI Yes G190A causes high level resistance to NVP, intermediate resistance to EFV, and increased DLV susceptibility. It has no effect on ETR susceptibility but was associated with a decreased response to ETR in the DUET studies. 190 CTV NNRTI Yes G190C/T/V are rare mutations that cause high-level resistance to NVP and EFV and increased susceptibility to DLV. Their effect on ETR is not known. 190 EQ NNRTI Yes G190E/Q cause high-level resistance to NVP and EFV and intermediate resistance to DLV. G190E + Y181C is associated with >100-fold decreased ETR susceptibility. 190 S NNRTI Yes G190S causes high-level resistance to NVP and EFV and increases DLV susceptibility. Although it was on the list of 13 mutations associated with decreased ETR response in the DUET studies, it does not appear to decrease ETR susceptibility. 190 NOT ACEQSTV NNRTI G190A/S/E/Q/T/V/C are NNRTI-resistance mutations. $listMutsIn{190(NOT ACEQSTV)} is a highly unusual mutation at this position. 210 FS NRTI Yes L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. L210F/S occur rarely and are of unknown significance. 210 W NRTI Yes L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. 210 NOT FSW NRTI L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. $listMutsIn{210(NOT FSW)} is a highly unusual mutation at this position. 215 SCDEIV NRTI Yes T215S/C/D/E/I/V are transitions between wild type and the mutations Y and F. Most do not reduce NRTI susceptibility but their presence may suggests that T215Y or F may also be present. 215 F NRTI Yes T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and to a lesser extent TDF. 215 Y NRTI Yes T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W. 215 NOT CDEFISVY NRTI T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W. T215S/C/D/E/I/V are transitions between wild type and the mutations Y and F. Most do not reduce NRTI susceptibility but their presence may suggests that T215Y or F may also be present. $listMutsIn{215(NOT CDEFISVY)} is a highly unusual mutation at this position. 219 EQ NRTI Yes K219Q/E decrease AZT and probably d4T susceptibility when present with K70R or T215Y/F but have little if any effect on the remaining NRTIs. 219 NR NRTI Yes K219N/R occur commonly in heavily NRTI-treated patients. Their effect on NRTI susceptibility is uncertain. 219 WDH NRTI Yes K219W/H/D are uncommon NRTI-selected mutations at this position. 219 NOT ENQRWDH NRTI K219Q/E/N/R/W/D/H are NNRTI-associated mutations. $listMutsIn{219(NOT ENQRWDH)} is an unusual mutation at this position. 221 Y NNRTI No H221Y is an uncommon NNRTI-associated mutation. Its phenotypic effect on current NNRTIs has not been studied. 221 NOT Y NNRTI H221Y is an uncommon NNRTI-associated mutation. Its phenotypic effect on current NNRTIs has not been studied. $listMutsIn{221(NOT Y)} is a highly unusual mutation at this position. 225 H NNRTI Yes P225H increases EFV resistance when present in combination with K103N. 225 NOT H NNRTI P225H increases EFV resistance when present in combination with K103N. $listMutsIn{225(NOT H)} is a highly unusual mutation at this position. 227 C NNRTI Yes F227C is a rare mutation which which has emerged in vitro with ETR. It has been associated with a wide range in phenotypic resistance to each of the NNRTIs. 227 L NNRTI Yes F227L usually occurs in combination with V106A and in this setting is associated with high level resistance to NVP and intermediate resistance to DLV and EFV. Its effect on ETR is not known. 227 NOT CL NNRTI F227LC are NNRTI-associated mutations. $listMutsIn{F227(NOT CL)} is a highly unusual mutation at this position. 230 L NNRTI Yes M230L causes intermediate-to-high-level resistance to each of the NNRTIs. It has been selected in vitro by ETR and reduces ETR susceptibility by about 3 to 10-fold depending on the assay. 230 NOT L NNRTI M230L causes intermediate-to-high-level resistance to each of the NNRTIs. $listMutsIn{230(NOT L)} is a highly unusual mutation at this position. 234 I NNRTI Yes L234I has been selected in vitro by ETR and it acts synergistically with Y181C to reduced susceptibility. Its clinical significance and effect on other NNRTIs is not known. 234 NOT I NNRTI L234I is an uncommon NNRTI associated mutation. $listMutsIn{234(NOT I)} is a highly unusual mutation at this position. 236 L NNRTI Yes P236L causes high-level DLV resistance. 236 NOT L NNRTI P236L causes high-level DLV resistance. $listMutsIn{236(NOT L)} is a highly unusual mutation at this position. 238 N NNRTI Yes K238T is an NNRTI-selected mutations that usually occur in combination with K103N in which case it causes high-level resistance to NVP, EFV, and DLV. Its effect on ETR is not known. K238N is a rarer NNRTI-selected mutation at this position. Its phenotypic effect is not known. 238 R Other Yes K238R is a naturally occurring variant that is common in some non-B subtypes and does not reduce NNRTI susceptibility. 238 T NNRTI Yes K238T is an NNRTI-selected mutations that usually occur in combination with K103N in which case it causes high-level resistance to NVP, EFV, and DLV. Its effect on ETR is not known. 238 NOT NRT NNRTI K238T/N are NNRTI-associated mutations. K238R is a common polymorphism that is not associated with NNRTIs. $listMutsIn{238(NOT NRT)} is a highly unusual mutation at this position. 318 F NNRTI Yes Y318F is an uncommon mutation that causes high-level DLV resistance and low/intermediate NVP resistance. 318 NOT F Y318F is an uncommon mutation that causes high-level DLV resistance and low/intermediate NVP resistance. $listMutsIn{318(NOT F)} is a highly unusual mutation at this position. 333 DE Other No G333D/E are polymorphisms that occur more frequently in persons receiving NRTIs than in untreated persons. They may facilitate AZT resistance in isolates that contain M184V and multiple TAMs. 333 NOT DE None 348 I NRTI No N348I causes low-level reductions in AZT and NVP susceptibility. 348 NOT I NRTI No N348I causes low-level reductions in AZT and NVP susceptibility. $listMutsIn{348(NOT I)} is an unusual mutation at this position.