HIVDB 6.0.5 PR PI RT NNRTI, NRTI IN INI 1 Susceptible S 2 Potential low-level resistance S 3 Low-level resistance I 4 Intermediate resistance I 5 High-level resistance R PI FPV/r,IDV/r,LPV/r,NFV,SQV/r,ATV/r,TPV/r,DRV/r NRTI AZT,D4T,DDI,3TC,FTC,ABC,TDF NNRTI NVP,DLV,EFV,ETR INI RAL,EVG (-INF TO 9 => 1, 10 TO 14 => 2, 15 TO 29 => 3, 30 TO 59 => 4, 60 TO INF => 5) The following $numberOfMutsIn{11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V} of the 11 darunavir/r POWER/DUET study mutations were present: $listMutsIn{11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V} (DeMeyer S et al, EHDRW 2008). 1 This sequence has $numberOfMutsIn{47V,54AMV,58E,74P,82LT,83D} major TPV/r-resistance mutations ($listMutsIn{47V,54AMV,58E,74P,82LT,83D}), $numberOfMutsIn{10V,36I,43T,46L,84V} minor TPV/r-resistance mutations ($listMutsIn{10V,36I,43T,46L,84V}), and $numberOfMutsIn{24I,50LV,54L,76V} mutations associated with increased TPV/r responsiveness ($listMutsIn{24I,50LV,54L,76V}). RESIST study (Baxter J et al J Virology 2006 and Scherer J et al EACS 2007). 1 The following $numberOfMutsIn{90I,98G,100I,101EP,106I,179DF,181CIV,190AS} of the 13 etravirine DUET study mutations were present: $listMutsIn{90I,98G,100I,101EP,106I,179DF,181CIV,190AS} (Katlama C et al, IAS 2007). 1 L10I/V/F/R/Y are associated with resistance to most PIs when present with other mutations. $listMutsIn{10ACDEGHKMNPQSTWdi} is a highly unusual mutation at this position. 1 L10I/V/F/R/Y are associated with resistance to most PIs when present with other mutations. L10I/V occur in 5-10% of untreated persons. L10F/R/Y are nonpolymorphic. 1 V11I is a PI-selected mutation. It is one of the 11 mutations associated with decreased response to DRV/r in the POWER trials. 1 I13V is a common polymorphism that is more common in treated than untreated subtype B isolates. In several subtypes, it is the consensus residue. 1 G16E is highly polymorphic. G16E was weakly associated with ATV/r therapy in one study. 1 K20R/M/I/T/V are associated with resistance to multiple PIs when present with other mutations. $listMutsIn{20ACDEFGHLNPQSWYdi} is a highly unusual mutation at this position. 1 K20R/M/I/T/V are associated with resistance to multiple PIs when present with other mutations. K20R/M/I are polymorphic; K20T/V are nonpolymorphic. 1 L23I is a rare substrate cleft mutation that causes low-level NFV resistance. $listMutsIn{23ACDEFGHKMNPQRSTVWYdi} is a highly unusual mutation at this position. 1 L23I is a rare substrate cleft mutation that causes low-level NFV resistance. 1 L24I is associated with reduced susceptibility to IDV/r and possibly LPV/r, SQV/r, and ATV/r when present with other mutations. It increases TPV/r susceptibility. L24F is a rare mutation at this position; its phenotypic effect is not known. $listMutsIn{24ACDEGHKMNPQRSTVWYdi} is a highly unusual mutation at this position. 1 L24I is associated with reduced susceptibility to IDV/r and possibly LPV/r, SQV/r, and ATV/r when present with other mutations. It increases TPV/r susceptibility. L24F is a rare mutation at this position; its phenotypic effect is not known. 1 L24I is associated with reduced susceptibility to IDV/r and possibly LPV/r, SQV/r, and ATV/r when present with other mutations. It increases TPV/r susceptibility. 1 D30N causes high-level resistance to NFV and potential low-level resistance to ATV/r. $listMutsIn{D30ACEFGHIKLMPQRSTVWYdi} is a highly unusual mutation at this position. 1 D30N causes high-level resistance to NFV and potential low-level resistance to ATV/r. 1 V32I is a substrate cleft mutation which is associated with reduced susceptibility to all PIs except SQV/r. $listMutsIn{V32ACDEFGHKLMNPQRSTWYdi} is a highly unusual mutation at this position. 1 V32I is a substrate cleft mutation which is associated with reduced susceptibility to all PIs except SQV/r. 1 L33F is selected by FPV/r, DRV/r, LPV/r, ATV/r, and TPV/r, and contribute resistance to these drugs. 1 L33F is selected by FPV/r, DRV/r, LPV/r, ATV/r, and TPV/r, and contribute resistance to these drugs. L33I is less common than L33F but may have a similar effect. 1 L33V is a polymorphism that does not appear to be related to PI therapy or drug resistance. 1 E35G is a nonpolymorphic mutation that is selected by NFV and which is weakly associated with decreased virological response to TPV/r. 1 M36I is weakly associated with PI resistance in subtype B viruses when present with other mutations. However, M36I is the consensus amino acid in most non-B subtypes. 1 M36I is weakly associated with PI resistance in subtype B viruses when present with other mutations. However, M36I is the consensus amino acid in most non-B subtypes. M36L/V/T are uncommon mutations at this position of unknown significance. 1 K43T is a nonpolymorphic PI-selected mutation. It was associated with a decreased virological response to TPV/r in the RESIST trials. 1 M46I/L decreases susceptibility to IDV/r, NFV, FPV/r, LPV/r, and ATV/r when present with other mutations. M46V is an uncommon PI-selected mutation at this position. $listMutsIn{46ACDEFGHKNPQRSTWYdi} is a highly unusual mutation at this position. 1 M46I/L decreases susceptibility to IDV/r, NFV, FPV/r, LPV/r, and ATV/r when present with other mutations. 1 M46I/L decreases susceptibility to IDV/r, NFV, FPV/r, LPV/r, and ATV/r when present with other mutations. M46V is an uncommon PI-selected mutation at this position. 1 I47A usually occurs with V32I and in this setting causes high-level LPV/r and FPV/r resistance and possibly decreased DRV/r susceptibility. 1 I47V decrease susceptibility to FPV/r, ATV/r, IDV/r, LPV/r, TPV/r, and DRV/r. I47A usually occurs with V32I and in this setting causes high-level LPV/r and FPV/r resistance and possibly decreased DRV/r susceptibility. $listMutsIn{47CDEFGHKLMNPQRSTWYdi} is a highly unusual mutation at this position. 1 I47V decrease susceptibility to FPV/r, ATV/r, IDV/r, LPV/r, TPV/r, and DRV/r. 1 G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance. G48M has not been well studied but may have a similar effect on ARV susceptibility. G48A/S/T/Q are rare PI-selected mutations. 1 G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance. G48M/A/S/T/Q are uncommon PI-selected mutations of uncertain effects. $listMutsIn{48CDEFHIKLNPRWYdi} is a highly unusual mutation at this position. 1 G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance. G48M is a less common mutation that may have a similar effect on ARV susceptibility. 1 G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance. 1 I50V causes intermediate-to-high-level resistance to FPV/r, low-intermediate resistance to LPV/r and DRV/r, and increased susceptibility to TPV/r. I50L causes intermediate-to-high level resistance to ATV/r and increased susceptibility to the remaining PIs. $listMutsIn{50ACDEFGHKMNPQRSTWYdi} is a highly unusual mutation at this position. 1 I50L causes intermediate-to-high level resistance to ATV/r and increased susceptibility to the remaining PIs. 1 I50V causes intermediate-to-high-level resistance to FPV/r, low-intermediate resistance to LPV/r and DRV/r, and increased susceptibility to TPV/r. 1 F53L is associated with decreased susceptibility to SQV/r and possibly ATV/r, IDV/r, NFV, and LPV/r. $listMutsIn{53ACDEGHIKMNPQRSTVWdi} is a highly unusual mutation at this position. 1 F53L is associated with decreased susceptibility to SQV/r and possibly ATV/r, IDV/r, NFV, and LPV/r. 1 F53L is associated with decreased susceptibility to SQV/r and possibly ATV/r, IDV/r, NFV, and LPV/r. F53Y is a rare treatment-associated variant at this position. 1 I54V/M/L/A/T/S have diverse effects on multiple PIs. $listMutsIn{54CDEFGHKNPQRWYdi} is a highly unusual mutation at this position. 1 I54L occurs in patients receiving FPV/r, LPV/r, and DRV/r and reduces susceptibility to these drugs and to NFV and possibly ATV/r. It increases TPV/r susceptibility. 1 I54M occurs in patients receiving FPV/r, LPV/r, and DRV/r and reduces susceptibility to these drugs and to the remaining PIs except possibly SQV/r. 1 I54T/A/S are PI-related mutations that appear to be associated with decreased susceptibility to each of the PIs. But their effects have not been as well studied as I54V, I54M, or I54L. 1 I54V contributes resistance to each of the PIs except TPV/r and DRV/r. 1 Q58E is a nonpolymorphic PI-selected mutation associated with decreased susceptibility to TPV/r and possibly other PIs. 1 D60E is a polymorphic mutation that is slightly more common in viruses from PI-treated compared with untreated persons. 1 I62V is a highly polymorphic mutation that is more common in PI-treated compared with untreated persons. 1 L63P is a common polymorphism that becomes even more common in persons receiving PIs. 1 A71T/V are polymorphisms that occur in 2-3% of untreated persons but which increase in frequency in persons receiving PIs. A71I/L are nonpolymorphic mutations that occur in viruses with multiple PI-resistance mutations. 1 G73S/T/C/A are selected by and appear to be associated with decreased susceptibility to most, if not all, PIs. Their effect on SQV/r and NFV and possibly ATV/r appears to be greater than their effect on other PIs. 1 T74P is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It has been associated with decreased virological response to TPV/r and to a lesser extent DRV/r but is probably associated with decreased susceptibility to multiple PIs. 1 T74S is associated with reduced NFV susceptibility. It occurs in untreated persons with subtype C viruses. 1 L76V reduces susceptibility to FPV/r, IDV/r, LPV/r, and DRV/r and increases susceptibility to SQV/r, ATV/r, and TPV/r. $listMutsIn{76ACDEFGHIKMNPQRSTWYdi} is a highly unusual mutation at this position. 1 L76V reduces susceptibility to FPV/r, IDV/r, LPV/r, and DRV/r and increases susceptibility to SQV/r, ATV/r, and TPV/r. 1 V77I is a common polymorphism that is associated with NFV therapy. 1 V82A reduces susceptibility to IDV/r and LPV/r. With other mutations it is associated with reduced susceptibility to NFV, ATV/r, SQV/r, and FPV/r. 1 V82C is a rare mutation that occurs primarily in protease genes containing multiple other PI-resistance mutations. 1 V82A/T/F/L/M/S/C have diverse effects on multiple PIs. $listMutsIn{82DEGHKNPQRWYdi} is a highly unusual mutation at this position. 1 V82F reduces susceptibility to IDV/r, LPV/r, FPV/r, and possibly DRV/r. With other mutations it is associated with reduced susceptibility to NFV, ATV/r, SQV/r, and possibly TPV/r. 1 V82I is a polymorphism that is common in some non-B subtypes; it has little if any effect on PI susceptibility. 1 V82L is a rare TPV/r-selected mutation which decreases TPV/r susceptibility. Its effect on other PIs has not been characterized. 1 V82M reduces IDV/r susceptibility in subtype G viruses. Its effect on other PIs has not been studied. 1 V82S probably has a similar effect to V82T which reduces susceptibility to IDV/r, LPV/r, and TPV/r and with other mutations is associated with reduced susceptibility to NFV, ATV/r, FPV/r, and SQV/r. 1 V82T reduces susceptibility to IDV/r, LPV/r, and TPV/r. With other mutations it is associated with reduced susceptibility to NFV, ATV/r, FPV/r, and SQV/r. 1 N83D is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It has been associated with decreased virological response to TPV/r. Its effect on other PIs is not known. $listMutsIn{83ACEFGHIKLMPQRSTVWYdi} is a highly unusual mutation at this position. 1 N83D is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It has been associated with decreased virological response to TPV/r. Its effect on other PIs is not known. 1 I84V causes intermediate/high-level resistance to ATV/r, FPV/r, IDV/r, NFV, and SQV/r; and low-level resistance to LPV/r, TPV/r, and DRV/r. I84A/C are rare mutations that like I84V appear to reduce susceptibility to each of the PIs. 1 I84V causes intermediate/high-level resistance to ATV/r, FPV/r, IDV/r, NFV, and SQV/r; and low-level resistance to LPV/r, TPV/r, and DRV/r. I84A/C are rare mutations that like I84V appear to reduce susceptibility to each of the PIs. $listMutsIn{84DEFGHKLMNPQRSTWYdi} is a highly unusual mutation at this position. 1 I84V causes intermediate/high-level resistance to ATV/r, FPV/r, IDV/r, NFV, and SQV/r; and low-level resistance to LPV/r, TPV/r, and DRV/r. 1 I85V is a nonpolymorphic PI-selected mutation. 1 N88D/S/T/G have diverse effects on several PIs. $listMutsIn{88ACEFHIKLMPQRVWYdi} is a highly unusual mutation at this position. 1 N88D is selected by NFV and, in combination with D30N, increases NFV resistance. 1 N88S causes high-level resistance to NFV and ATV/r and low-level resistance to IDV/r; it increases susceptibility to FPV/r. N88T/G are rare PI-selected mutations that may have an effect similar to but less pronounced than N88S. 1 N88S causes high-level resistance to NFV and ATV/r and low-level resistance to IDV/r; it increases susceptibility to FPV/r. 1 L89I is a minimally polymorphic PI-selected mutation of uncertain effect on PI susceptibility. 1 L89M is a common polymorphism that is not associated with decreased PI susceptibility. 1 L89T is a nonpolymoprhic PI-selected mutation of uncertain effect on PI susceptibility. 1 L89V is a nonpolymorphic PI-selected accessory mutation which emerges during treatment with DRV/r and NFV. It is also one of the 11 mutations associated with decreased response to DRV/r in the POWER trials. 1 L90M causes resistance to NFV, SQV/r, ATV/r, and IDV/r. When present with other mutations it also decreases the activity of FPV/r and LPV/r. $listMutsIn{90ACDEFGHIKNPQRSTVWYdi} is a highly unusual mutation at this position. 1 L90M causes resistance to NFV, SQV/r, ATV/r, and IDV/r. When present with other mutations it also decreases the activity of FPV/r and LPV/r. 1 I93L is a common polymorphism. It is the consensus residue in most subtypes. In subtype B, it is weakly associated with PI treatment. 1 I93M is a rare PI-associated mutation; its effect on PI susceptibility is not known. 1 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{41ACDEFGHIKNPQRSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 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. 1 A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known. $listMutsIn{62CDEFGHIKLMNPQRSTWYdi} is a highly unusual mutation at this position. 1 A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known. 1 K65R/N are known NRTI-resistance mutations. $listMutsIn{65ACDEFGHILMPQSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF, and low-level resistance to d4T. K65R causes AZT hypersusceptibility. 1 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{67ACFHIKLMPQRSTVWYi} is a highly unusual mutation at this position. 1 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. 1 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. 1 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. 1 T69D/N/S/G/A/I are NRTI-selected mutations. $listMutsIn{69CEFHKLMPQRVWYd} is a highly unusual mutation at this position. 1 T69D, a mutation originally identified for its role in causing ddC reistance, is associated with decreased susceptibility to ddI and d4T. 1 T69G occurs in isolates with a deletion at position 67 but its effect on NRTI susceptibility is not known. 1 T69N/S/A/I are NRTI-selected mutations but their effect on NRTI susceptibility is not known. 1 Deletions at codon 69 occur at a frequency of about 0.1%. Their phenotypic and clinical significance is not known. 1 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. 1 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{70ACDFHILMNPQSTVWYdi} is an unusual mutation at this position. 1 K70E/G reduces TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility. 1 K70R causes low-level AZT, d4T, and possibly TDF resistance. 1 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{74ACDEFGHKMNPQRSTWYdi} is a highly unusual mutation at this position. 1 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. 1 L74V reduces susceptibility to ddI and ABC susceptibility and increases susceptibility AZT and TDF. 1 V75M/T/A/S/I are NRTI-selected mutations. $listMutsIn{75CDEFGHKNPQRWYdi} is a highly unusual mutation at this position. 1 V75I increases multinucleoside resistance caused by Q151M when present with F77L and F116Y; its effect in the absence of Q151M is not known. 1 V75L does not appear to be associated with reduced NRTI susceptibility. 1 V75T/M/A/S reduce d4T and possibly ddI susceptibility. 1 F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y. $listMutsIn{77ACDEGHIKMNPQRSTVWYdi} is a highly unusual mutation at this position 1 F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y; its effect in the absence of Q151M is not known. 1 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. 1 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. 1 A98S is a common polymorphism that does not reduce NNRTI susceptibility. 1 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{100ACDEFGHKMNPQRSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 K101E/P/N/H/Q are NNRTI-selected mutations. $listMutsIn{101ACDFGILMSTVWYdi} is a highly unusual mutation at this position. 1 K101E causes intermediate resistance to NVP and DLV and low-level resistance to EFV and ETR. 1 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. 1 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. 1 K101Q is weakly associated with NNRTI therapy and minimally reduces susceptibility to each of the NNRTIs. 1 K101R is an uncommon polymorphism that has not been associated with decreased NNRTI susceptibility. 1 K103N/S/T/H are NNRTI-resistance mutations. K103R/E/Q are variants that usually do not cause NNRTI resistance. $listMutsIn{103ACDFGILMPVWYdi} is a highly unusual mutation at this position. 1 K103E/Q are rare mutations that have not been associated with resistance to the current NNRTIs. 1 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. 1 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. 1 K103S causes high-level resistance to NVP and intermediate/high-level resistance to DLV and EFV. 1 K103T/H are rare mutations that appear to be associated with intermediate/high-level resistance to NVP, DLV, and EFV. 1 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. 1 V106A/M are NNRTI-resistance mutations. V106I/L are polymorphisms that do not appear to cause NNRTI resistance. $listMutsIn{106CDEFGHKNPQRSTWYdi} is a highly unusual mutation at this position. 1 V106I is a common polymorphism that was associated with decreased ETR response in the DUE study. However, it does not decrease NNRTI susceptibility. 1 V106L is a rare polymorphism that does not appear to be associated with NNRTI resistance. 1 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. 1 V108I causes low-level reductions in susceptibility to each of the NNRTIs except ETR. It occasionally occurs in the absence of NNRTI therapy. $listMutsIn{108ACDEFGHKLMNPQRSTWYdi} is a highly unusual mutation at this position. 1 V108I causes low-level reductions in susceptibility to each of the NNRTIs except ETR. It occasionally occurs in the absence of NNRTI therapy. 1 Y115F causes intermediate resistance to ABC and low-level resistance to TDF. $listMutsIn{115ACDEGHIKLMNPQRSTVWdi} is a highly unusual mutation at this position. 1 Y115F causes intermediate resistance to ABC and low-level resistance to TDF. 1 F116Y increases multinucleoside resistance caused by Q151M when present with F77L or V75I; its effect in the absence of Q151M is not known. $listMutsIn{116ACDEGHIKLMNPQRSTVWdi} is a highly unusual mutation at this position. 1 F116Y increases multinucleoside resistance caused by Q151M when present with F77L or V75I; its effect in the absence of Q151M is not known. 1 $listMutsIn{V118ACDEFGHKLMNPQRSTWYdi} is a highly unusual mutation at this position. 1 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. 1 E138A is a polymorphism that has been recently added to the list of mutations associated with decreased ETR response in the DUET studies. 1 E138AGKQ are weakly assocated with decreased ETR suscepitibility. $listMutsIn{138CDFHILMNPRSTVWYdi} is an unusual mutation at this position. 1 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. 1 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. 1 E138Q is weakly associated with NNRTI therapy. It may contribute to decreased NNRTI susceptibility in certain genetic contexts. 1 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{151ACDEFGHIKNPRSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 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. 1 $listMutsIn{V179ACGHKLMNPQRSWYdi} is an unusual mutation at this position. 1 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. 1 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. 1 V179I is a common polymorphism which occurs more commonly in NNRTI-treated isolates. However, it does not reduce NNRTI susceptibility. 1 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 1 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{181ADEFGHKLMNPQRTWdi} is a highly unusual mutation at this position. 1 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. 1 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. 1 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{184ACDEFGHKLNPQRSTWYdi} is a highly unusual mutation at this position. 1 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. 1 Y188L/H/C are NNRTI-resistance mutations. $listMutsIn{188ADEGIKMNPQRSTVWdi} is a highly unusual mutation at this position. 1 Y188C causes high-level resistance to NVP and low-level resistance to EFV and DLV; its effect on ETR is not known. 1 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. 1 Y188H causes intermediate resistance to NVP, EFV, and DLV and has been selected in vitro by ETR. 1 Y188L causes high-level resistance to NVP and EFV, intermediate resistance to DLV, and potentially low-level resistance to ETR. 1 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. 1 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. 1 G190A/S/E/Q/T/V/C are NNRTI-resistance mutations. $listMutsIn{190DFHIKLMNPRWYdi} is a highly unusual mutation at this position. 1 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. 1 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. 1 L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. $listMutsIn{210ACDEGHIKMNPQRTVYdi} is a highly unusual mutation at this position. 1 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. 1 L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. 1 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{215AGHKLMNPQRWdi} is a highly unusual mutation at this position. 1 T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and to a lesser extent TDF. 1 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. 1 T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W. 1 K219Q/E/N/R/W/D/H are NNRTI-associated mutations. $listMutsIn{219ACFGILMPSTVYdi} is an unusual mutation at this position. 1 K219N/R occur commonly in heavily NRTI-treated patients. Their effect on NRTI susceptibility is uncertain. 1 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. 1 K219W/H/D are uncommon NRTI-selected mutations at this position. 1 H221Y is an uncommon NNRTI-associated mutation. Its phenotypic effect on current NNRTIs has not been studied. $listMutsIn{221ACDEFGIKLMNPQRSTVWdi} is a highly unusual mutation at this position. 1 H221Y is an uncommon NNRTI-associated mutation. Its phenotypic effect on current NNRTIs has not been studied. 1 P225H increases EFV resistance when present in combination with K103N. $listMutsIn{225ACDEFGIKLMNQRSTVWYdi} is a highly unusual mutation at this position. 1 P225H increases EFV resistance when present in combination with K103N. 1 F227LC are NNRTI-associated mutations. $listMutsIn{F227ADEGHIKMNPQRSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 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. 1 M230L causes intermediate-to-high-level resistance to each of the NNRTIs. $listMutsIn{230ACDEFGHIKNPQRSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 L234I is an uncommon NNRTI associated mutation. $listMutsIn{234ACDEFGHKMNPQRSTVWYdi} is a highly unusual mutation at this position. 1 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. 1 P236L causes high-level DLV resistance. $listMutsIn{236ACDEFGHIKMNQRSTVWYdi} is a highly unusual mutation at this position. 1 P236L causes high-level DLV resistance. 1 K238T/N are NNRTI-associated mutations. K238R is a common polymorphism that is not associated with NNRTIs. $listMutsIn{238ACDEFGHILMPQSVWYdi} is a highly unusual mutation at this position. 1 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. 1 K238R is a naturally occurring variant that is common in some non-B subtypes and does not reduce NNRTI susceptibility. 1 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. 1 Y318F is an uncommon mutation that causes high-level DLV resistance and low/intermediate NVP resistance. $listMutsIn{318ACDEGHIKLMNPQRSTVWdi} is a highly unusual mutation at this position. 1 Y318F is an uncommon mutation that causes high-level DLV resistance and low/intermediate NVP resistance. 1 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. 1 N348I causes low-level reductions in AZT and NVP susceptibility. $listMutsIn{348ACDEFGHKLMPQRSTVWYdi} is an unusual mutation at this position. 1 N348I causes low-level reductions in AZT and NVP susceptibility. 1 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{51ACDEFGIKLMNPQRSTVWdi} is an unusual mutation at this position. 1 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) 1 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). 1 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. 1 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). 1 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). 1 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{72ACDEFGHKLMNPQRSTVWYdi} is an unusual mutation at this position. 1 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). 1 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). 1 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{92ACDFGHIKLMNPRSTWYdi} is an unusual mutation at this position. 1 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). 1 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{95ACDEFGHILMNPRSTVWYdi} is an unusual mutation at this position. 1 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) 1 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) 1 H114Y is a nonpolymorphic accessory resistance mutation reported to be selected in vitro by EVG (Goethals et al. 2008). $listMutsIn{114ACDEFGIKLMNPQRSTVWdi} is an unusual mutation at this position. 1 H114Y is a nonpolymorphic accessory resistance mutation reported to be selected in vitro by EVG (Goethals et al. 2008). 1 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{121ACDEGHIKLMNPQRSTVWdi} is an unusual mutation at this position. 1 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 1 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). 1 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{128CDEFGHIKLMNPQRSVWYdi} is an unusual mutation at this position. 1 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) 1 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{138CDFGHILMNPQRSTVWYdi} is an unusual mutation at this position. 1 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). 1 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{140DEFHIKLMNPQRTVWYdi} is an unusual mutation at this position. 1 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). 1 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{143ADEFGIKLMNPQSTVWdi} is an unusual mutation at this position. 1 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). 1 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. 1 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{145ACDEFGHIKLMNQRTVWYdi} is an unusual mutation at this position. 1 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). 1 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{146ACDEFGHIKLMNRSTVWYdi} is an unusual mutation at this position. 1 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. 1 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{147ACDEFHIKLMNPQRTVWYdi} is an unusual mutation at this position. 1 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). 1 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{148ACDEFGILMNPSTVWYdi} is an unusual mutation at this position. 1 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). 1 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{151CDEFGHKLMNPQRSTWYdi} is an unusual mutation at this position. 1 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). 1 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{153ACDEFGHIKLMNPQRTVWdi} is an unusual mutation at this position. 1 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). 1 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). 1 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. 1 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). 1 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). 1 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{157ACDFGHIKLMNPRSTVWYdi} is an unusual mutation at this position. 1 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. 1 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). 1 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{201ACDEFGHKLMNPQRSTWYdi} is an unusual mutation at this position. 1 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). 1 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. 1 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{206ACDEFGHIKLMNPQRVWYdi} is an unusual mutation at this position. 1 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). 1 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. 1 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{263ACDEFGHILMNPQSTVWYdi} is an unusual mutation at this position. 1 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) 1 DLV delavirdine SCORE FROM (98G => 10, 100I => 40, 101P => 40, 101E => 30, 101HN => 15, 101Q => 5, 103NST => 60, 103R => 5, 106M => 60, 106A => 50, 108I => 10, 138K => 15, 138Q => 10, 138AG => 5, 179F => 30, 179DE => 10, 181CISV => 60, 188CHL => 30, 190EQ => 30, 225H => 15, 227C => 30, 227L => 5, 230L => 60, 234I => 10, 236L => 60, 238NT => 30, 318F => 60 ) EFV efavirenz SCORE FROM (98G => 5, 100I => 40, 101P => 40, 101E => 15, 101HN => 10, 101Q => 5, 103NST => 60, 103R => 5, 106M => 60, 106A => 30, 108I => 10, 138KQ => 10, 138AG => 5, 179F => 15, 179DE => 10, 181CISV => 30, 188L => 60, 188CH => 30, 190CEQSTV => 60, 190A => 40, 225H => 30, 227C => 15, 227L => 5, 230L => 45, 234I => 10, 238NT => 15, 318F => 10 ) NVP nevirapine SCORE FROM (98G => 10, 100I => 40, 101P => 40, 101E => 30, 101HN => 15, 101Q => 5, 103NST => 60, 103R => 5, 106AM => 60, 108I => 10, 138K => 15, 138Q => 10, 138AG => 5, 179F => 30, 179DE => 10, 181CISV => 60, 188CL => 60, 188H => 30, 190ACEQSTV => 60, 225H => 15, 227C => 30, 227L => 15, 230L => 60, 234I => 10, 238NT => 30, 318F => 30 ) ETR etravirine SCORE FROM (98G => 5, 100I => 20, 101P => 20, 101E => 15, 101HNQ => 5, 103NST => 10, 106M => 10, 106A => 5, 138KQ => 10, 138AG => 5, 179F => 25, 179DE => 10, 181CIV => 35, 181S => 20, 188L => 20, 188H => 15, 188C => 10, 190E => 25, 190AQS => 15, 190CTV => 10, 225H => 10, 227C => 15, 227L => 5, 230L => 20, 234I => 10, 238NT => 5, 318F => 10 ) SELECT ATLEAST 1 FROM (90I,98G,100I,101EP,106I,179DF,181CIV,190AS) 3TC lamivudine SCORE FROM (41L => 4, 44AD => 5, 65R => 30, 65N => 15, 67d => 15, 69i => 25, 69d => 15, 69DGN => 5, 69AEIS => 2, 70E => 15, 70G => 10, 75I => 5, 77L => 5, 116Y => 5, 118I => 5, 151M => 15, 151L => 10, 184IV => 60, 210W => 4, 215FY => 4 ) FTC emtricitabine SCORE FROM (41L => 4, 44AD => 5, 65R => 30, 65N => 15, 67d => 15, 69i => 25, 69d => 15, 69DGN => 5, 69AEIS => 2, 70E => 15, 70G => 10, 75I => 5, 77L => 5, 116Y => 5, 118I => 5, 151M => 15, 151L => 10, 184IV => 60, 210W => 4, 215FY => 4 ) ABC abacavir SCORE FROM (41L => 12, 44AD => 2, 62V => 2, 65R => 30, 65N => 10, 67d => 25, 67GN => 8, 67EHST => 5, 69i => 30, 69d => 25, 69DGN => 5, 69AEIS => 2, 70E => 25, 70G => 20, 74V => 30, 74I => 20, 75AIMST => 5, 75L => 2, 77L => 10, 115F => 30, 116Y => 10, 118I => 2, 151M => 40, 151L => 20, 184IV => 12, 210W => 12, 215FY => 20, 215CDEISV => 10, 219W => 5, (184V AND 74V) => 20, (184V AND 65R) => 20 ) AZT zidovudine SCORE FROM (41L => 15, 44AD => 2, 62V => 2, 65R AND EXCLUDE 65(NOT R) => -5, 67d => 30, 67GN => 15, 67E => 10, 67HST => 5, 69di => 30, 69DGN => 5, 69AEIS => 2, 70R => 18, 70NST => 5, 74V AND EXCLUDE 74(NOT V) => -5, 75AIMST => 5, 75L => 2, 77L => 10, 100I AND EXCLUDE 100(NOT I) => -4, 116Y => 10, 118I => 2, 151M => 50, 151L => 20, 181C AND EXCLUDE 181(NOT C) => -4, 184IV AND EXCLUDE 184(NOT IV) => -8, 210W => 15, 215FY => 35, 215CDEISV => 20, 219ENQ => 15, 219RW => 10, 333DE => 5 ) D4T stavudine SCORE FROM (41L => 15, 44AD => 2, 62V => 2, 65R => 15, 67d => 30, 67GN => 12, 67E => 10, 67HST => 5, 69di => 30, 69DGN => 10, 69AEIS => 2, 70R => 10, 70NST => 5, 75T => 50, 75M => 30, 75S => 20, 75A => 15, 75I => 10, 75L => 2, 77L => 10, 116Y => 10, 118I => 2, 151M => 50, 151L => 20, 184IV AND EXCLUDE 184(NOT IV) => -5, 210W => 15, 215FY => 30, 215CDEISV => 20, 219ENQW => 10, 219R => 5 ) DDI didanosine SCORE FROM (41L => 12, 44AD => 2, 62V => 2, 65R => 30, 65N => 15, 67d => 25, 67GN => 8, 67EHST => 5, 69i => 40, 69d => 25, 69DG => 20, 69N => 10, 69AIS => 5, 69E => 2, 70EG => 25, 74V => 60, 74I => 30, 75MT => 20, 75AIS => 10, 75L => 2, 77L => 10, 116Y => 10, 118I => 2, 151M => 50, 151L => 20, 184IV => 5, 210W => 12, 215FY => 20, 215CDEISV => 10, 219W => 5 ) TDF tenofovir SCORE FROM (41L => 12, 44AD => 2, 62V => 2, 65R => 40, 65N => 15, 67d => 15, 67GHNST => 5, 69i => 40, 69d => 15, 69DGN => 5, 69AEIS => 2, 70E => 25, 70G => 15, 70R => 8, 75AIMT => 5, 75L => 2, 77L => 5, 100I AND EXCLUDE 100(NOT I) => -4, 115F => 10, 116Y => 5, 118I => 2, 151M => 15, 151L => 10, 181C AND EXCLUDE 181(NOT C) => -4, 184IV AND EXCLUDE 184(NOT IV) => -8, 210W => 12, 215Y => 20, 215CDEFISV => 10, 219W => 5 ) FPV/r fosamprenavir/r SCORE FROM (10F => 4, 10IRVY => 2, 11I => 5, 24I => 3, 32I => 30, 33F => 10, 43T => 2, 46IL => 12, 46V => 5, 47AV => 30, 48MV => 5, 50V => 60, 50L AND EXCLUDE 50(NOT L) => -5, 53L => 3, 54LM => 30, 54ASTV => 10, 71ILTV => 2, 73ACST => 2, 74P => 5, 76V => 35, 82ACFLMST => 10, 84ACV => 35, 88S AND EXCLUDE 88(NOT S) => -10, 89V => 8, 90M => 15 ) DRV/r darunavir/r SCORE FROM (10F => 2, 11I => 5, 32I => 15, 33F => 5, 46IL => 4, 46V => 2, 47AV => 10, 50V => 20, 50L AND EXCLUDE 50(NOT L) => -5, 54M => 20, 54L => 15, 54STV => 4, 54A => 3, 73ACST => 2, 74P => 5, 76V => 15, 82F => 6, 82ACLMST => 3, 84ACV => 10, 88S AND EXCLUDE 88(NOT S) => -5, 89V => 5, 90M => 6 ) SELECT ATLEAST 1 FROM (11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V) IDV/r indinavir/r SCORE FROM (10F => 4, 10IRVY => 2, 24I => 5, 32I => 12, 43T => 2, 46IL => 12, 46V => 5, 47AV => 10, 48MV => 10, 48AEQST => 5, 50L AND EXCLUDE 50(NOT L) => -5, 53L => 3, 53Y => 2, 54ASTV => 12, 54LM => 10, 71ILTV => 2, 73ACST => 5, 74P => 5, 76V => 20, 82AFST => 35, 82M => 15, 82CL => 10, 83D => 5, 84ACV => 35, 88S => 10, 88DGT => 5, 89V => 2, 90M => 30 ) LPV/r lopinavir/r SCORE FROM (10F => 4, 10IRVY => 2, 24I => 3, 32I => 12, 33F => 5, 43T => 2, 46IL => 10, 46V => 5, 47A => 50, 47V => 15, 48MV => 10, 48AEQST => 5, 50V => 20, 50L AND EXCLUDE 50(NOT L) => -5, 53L => 3, 53Y => 2, 54ALMSTV => 12, 71ILTV => 2, 73ACST => 2, 74P => 5, 76V => 20, 82AFST => 25, 82CLM => 10, 84ACV => 15, 89V => 2, 90M => 10 ) ATV/r atazanavir/r SCORE FROM (10F => 4, 10IRVY => 2, 24I => 3, 30N => 10, 32I => 12, 33F => 5, 43T => 2, 46IL => 12, 46V => 5, 47AV => 5, 48MV => 30, 48AEQST => 5, 50L => 60, 53L => 5, 53Y => 2, 54ALMSTV => 12, 58E => 5, 71ILTV => 2, 73ACST => 10, 74P => 5, 76V AND EXCLUDE 76(NOT V) => -5, 82FST => 20, 82A => 15, 82CLM => 10, 83D => 5, 84ACV => 35, 88S => 60, 88DGT => 10, 89V => 2, 90M => 20 ) TPV/r tipranavir/r SCORE FROM (24I AND EXCLUDE 24(NOT I) => -2, 32I => 5, 33F => 10, 35G => 2, 43T => 5, 46IL => 4, 46V => 2, 47V => 15, 47A => 10, 50LV AND EXCLUDE 50(NOT LV) => -5, 54AMV => 15, 54ST => 10, 54L AND EXCLUDE 54(NOT L) => -8, 58E => 15, 73ACST => 2, 74P => 15, 76V AND EXCLUDE 76(NOT V) => -8, 82L => 60, 82T => 40, 82S => 15, 82ACFM => 6, 83D => 15, 84ACV => 15, 90M => 6 ) SELECT ATLEAST 1 FROM (47V,54AMV,58E,74P,82LT,83D,10V,36I,43T,46L,84V,24I,50LV,54L,76V) NFV nelfinavir SCORE FROM (10F => 4, 10IRVY => 2, 23I => 15, 24I => 3, 30N => 60, 32I => 10, 35G => 5, 43T => 2, 46IL => 30, 46V => 10, 47AV => 15, 48MV => 30, 48AEQST => 15, 50V => 10, 50L AND EXCLUDE 50(NOT L) => -5, 53L => 3, 53Y => 2, 54ALMSTV => 15, 58E => 5, 71ILTV => 2, 73ACST => 10, 74PS => 10, 76V => 5, 82AFST => 35, 82CLM => 10, 83D => 5, 84ACV => 40, 88S => 60, 88DGT => 30, 89V => 10, 90M => 60 ) SQV/r saquinavir/r SCORE FROM (10F => 4, 10IRVY => 2, 24I => 3, 43T => 2, 46ILV => 5, 48MV => 60, 48AEQST => 30, 50L AND EXCLUDE 50(NOT L) => -5, 53L => 10, 53Y => 2, 54ASTV => 15, 54LM => 10, 71ILTV => 2, 73ACST => 10, 74P => 5, 76V AND EXCLUDE 76(NOT V) => -5, 82ACFLMST => 10, 83D => 5, 84ACV => 40, 88D => 10, 88GST => 5, 89V => 2, 90M => 40 ) RAL raltegravir SCORE FROM (66AK => 15, 74M => 5, 92QV => 30, 95K => 5, 97A => 5, 121Y => 30, 125K => 5, 138AK => 15, 140ACS => 30, 143CR => 60, 143H => 30, 148HKR => 60, 151AI => 5, 155H => 60, 155S => 15, 157Q => 10, 163KR => 5 ) EVG elvitegravir SCORE FROM (51Y => 15, 66AIK => 60, 74M => 5, 92QV => 60, 95K => 5, 97A => 5, 114Y => 5, 121Y => 30, 125K => 5, 128T => 5, 138AK => 15, 140ACS => 30, 145S => 60, 146P => 30, 147G => 45, 148HKR => 60, 151AI => 5, 153Y => 15, 155H => 60, 155S => 30, 157Q => 10, 263K => 15 ) PR 10(NOT LIVFRY) 10IVFRY 11I 13V 16E 20(NOT KRIMTV) 20RMITV 23(NOT LI) 23I 24(NOT LFI) 24F 24I 30(NOT DN) 30N 32(NOT VI) 32I 33F 33I 33V 35G 36I 36LTV 43T 46(NOT MILV) 46IL 46V 47A 47(NOT IAV) 47V 48ASTQ 48(NOT GVMASTQ) 48M 48V 50(NOT ILV) 50L 50V 53(NOT FLY) 53L 53Y 54(NOT IALMSTV) 54L 54M 54TAS 54V 58E 60E 62V 63P 71TVIL 73STCA 74P 74S 76(NOT LV) 76V 77I 82A 82C 82(NOT VATIFLMSC) 82F 82I 82L 82M 82S 82T 83(NOT ND) 83D 84AC 84(NOT IACV) 84V 85V 88(NOT NDGST) 88D 88GT 88S 89I 89M 89T 89V 90(NOT LM) 90M 93L 93M RT 41(NOT ML) 41L 44AD 62(NOT AV) 62V 65(NOT KNR) 65N 65R 67(NOT DEGNd) 67EG 67N 67d 69(NOT TADGINSi) 69D 69G 69NSAI 69d 69i 70(NOT KEGR) 70EG 70R 74(NOT LIV) 74I 74V 75(NOT VAIMSTL) 75I 75L 75TMAS 77(NOT FL) 77L 90I 98G 98S 100(NOT LI) 100I 101(NOT KEHNPQR) 101E 101HN 101P 101Q 101R 103(NOT KEHNQRST) 103EQ 103N 103R 103S 103TH 106A 106(NOT VAIML) 106I 106L 106M 108(NOT VI) 108I 115(NOT YF) 115F 116(NOT FY) 116Y 118(NOT VI) 118I 138A 138(NOT EAGKQ) 138G 138K 138Q 151(NOT QLM) 151L 151M 179(NOT VDEFIT) 179DE 179F 179I 179T 181(NOT YCISV) 181CIV 181S 184(NOT MIV) 184VI 188(NOT YCHLF) 188C 188F 188H 188L 190A 190CTV 190(NOT GACEQSTV) 190EQ 190S 210(NOT LFSW) 210FS 210W 215(NOT TCDEFISVY) 215F 215SCDEIV 215Y 219(NOT KENQRWDH) 219NR 219QE 219WDH 221(NOT HY) 221Y 225(NOT PH) 225H 227(NOT FCL) 227C 227L 230(NOT ML) 230L 234(NOT LI) 234I 236(NOT PL) 236L 238(NOT KNRT) 238N 238R 238T 318(NOT YF) 318F 333DE 348(NOT NI) 348I IN 51(NOT HY) 51Y 66AK 66(NOT TIAK) 66I 68VI 72(NOT II) 72I 74M 92(NOT EQV) 92QV 95(NOT QK) 95K 97A 114(NOT HY) 114Y 121(NOT FY) 121Y 125K 128(NOT AT) 128T 138(NOT EKA) 138KA 140(NOT GSAC) 140SAC 143(NOT YCRH) 143CR 143H 145(NOT PS) 145S 146(NOT QP) 146P 147(NOT SG) 147G 148(NOT QHKR) 148HKR 151(NOT VIA) 151IA 153(NOT SY) 153Y 154IL 155(NOT NHS) 155H 155S 157(NOT EQ) 157Q 163RK 201(NOT VI) 201I 203M 206(NOT TS) 206S 230NR 263(NOT RK) 263K