|
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.
|
|
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.
|
|
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.
|
|
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.
|
|
A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known.
|
|
K65R/N are known NRTI-resistance mutations. $listMutsIn{65ACDEFGHILMPQSTVWYdi} is a highly unusual mutation at this position.
|
|
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.
|
|
K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF, and low-level resistance to d4T. K65R causes AZT hypersusceptibility.
|
|
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.
|
|
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.
|
|
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.
|
|
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.
|
|
T69D/N/S/G/A/I are NRTI-selected mutations. $listMutsIn{69CEFHKLMPQRVWYd} is a highly unusual mutation at this position.
|
|
T69D, a mutation originally identified for its role in causing ddC reistance, is associated with decreased susceptibility to ddI and d4T.
|
|
T69G occurs in isolates with a deletion at position 67 but its effect on NRTI susceptibility is not known.
|
|
T69N/S/A/I are NRTI-selected mutations but their effect on NRTI susceptibility is not known.
|
|
Deletions at codon 69 occur at a frequency of about 0.1%. Their phenotypic and clinical significance is not known.
|
|
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.
|
|
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.
|
|
K70E/G reduces TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility.
|
|
K70R causes low-level AZT, d4T, and possibly TDF resistance.
|
|
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.
|
|
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.
|
|
L74V reduces susceptibility to ddI and ABC susceptibility and increases susceptibility AZT and TDF.
|
|
V75M/T/A/S/I are NRTI-selected mutations. $listMutsIn{75CDEFGHKNPQRWYdi} is a highly unusual mutation at this position.
|
|
V75I increases multinucleoside resistance caused by Q151M when present with F77L and F116Y; its effect in the absence of Q151M is not known.
|
|
V75L does not appear to be associated with reduced NRTI susceptibility.
|
|
V75T/M/A/S reduce d4T and possibly ddI susceptibility.
|
|
F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y. $listMutsIn{77ACDEGHIKMNPQRSTVWYdi} is a highly unusual mutation at this position
|
|
F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y; its effect in the absence of Q151M is not known.
|
|
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.
|
|
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.
|
|
A98S is a common polymorphism that does not reduce NNRTI susceptibility.
|
|
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.
|
|
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.
|
|
K101E/P/N/H/Q are NNRTI-selected mutations. $listMutsIn{101ACDFGILMSTVWYdi} is a highly unusual mutation at this position.
|
|
K101E causes intermediate resistance to NVP and DLV and low-level resistance to EFV and ETR.
|
|
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.
|
|
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.
|
|
K101Q is weakly associated with NNRTI therapy and minimally reduces susceptibility to each of the NNRTIs.
|
|
K101R is an uncommon polymorphism that has not been associated with decreased NNRTI susceptibility.
|
|
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.
|
|
K103E/Q are rare mutations that have not been associated with resistance to the current NNRTIs.
|
|
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.
|
|
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.
|
|
K103S causes high-level resistance to NVP and intermediate/high-level resistance to DLV and EFV.
|
|
K103T/H are rare mutations that appear to be associated with intermediate/high-level resistance to NVP, DLV, and EFV.
|
|
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.
|
|
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.
|
|
V106I is a common polymorphism that was associated with decreased ETR response in the DUE study. However, it does not decrease NNRTI susceptibility.
|
|
V106L is a rare polymorphism that does not appear to be associated with NNRTI resistance.
|
|
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.
|
|
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.
|
|
V108I causes low-level reductions in susceptibility to each of the NNRTIs except ETR. It occasionally occurs in the absence of NNRTI therapy.
|
|
Y115F causes intermediate resistance to ABC and low-level resistance to TDF. $listMutsIn{115ACDEGHIKLMNPQRSTVWdi} is a highly unusual mutation at this position.
|
|
Y115F causes intermediate resistance to ABC and low-level resistance to TDF.
|
|
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.
|
|
F116Y increases multinucleoside resistance caused by Q151M when present with F77L or V75I; its effect in the absence of Q151M is not known.
|
|
$listMutsIn{V118ACDEFGHKLMNPQRSTWYdi} is a highly unusual mutation at this position.
|
|
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.
|
|
E138A is a polymorphism that has been recently added to the list of mutations associated with decreased ETR response in the DUET studies.
|
|
E138AGKQ are weakly assocated with decreased ETR suscepitibility. $listMutsIn{138CDFHILMNPRSTVWYdi} is an unusual mutation at this position.
|
|
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.
|
|
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.
|
|
E138Q is weakly associated with NNRTI therapy. It may contribute to decreased NNRTI susceptibility in certain genetic contexts.
|
|
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.
|
|
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.
|
|
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{V179ACGHKLMNPQRSWYdi} is an unusual mutation at this position.
|
|
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.
|
|
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.
|
|
V179I is a common polymorphism which occurs more commonly in NNRTI-treated isolates. However, it does not reduce NNRTI susceptibility.
|
|
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
|
|
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.
|
|
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.
|
|
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.
|
|
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.
|
|
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.
|
|
Y188L/H/C are NNRTI-resistance mutations. $listMutsIn{188ADEGIKMNPQRSTVWdi} is a highly unusual mutation at this position.
|
|
Y188C causes high-level resistance to NVP and low-level resistance to EFV and DLV; its effect on ETR is not known.
|
|
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.
|
|
Y188H causes intermediate resistance to NVP, EFV, and DLV and has been selected in vitro by ETR.
|
|
Y188L causes high-level resistance to NVP and EFV, intermediate resistance to DLV, and potentially low-level resistance to ETR.
|
|
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.
|
|
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.
|
|
G190A/S/E/Q/T/V/C are NNRTI-resistance mutations. $listMutsIn{190DFHIKLMNPRWYdi} is a highly unusual mutation at this position.
|
|
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.
|
|
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.
|
|
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.
|
|
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.
|
|
L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y.
|
|
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.
|
|
T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and to a lesser extent TDF.
|
|
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.
|
|
T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W.
|
|
K219Q/E/N/R/W/D/H are NNRTI-associated mutations. $listMutsIn{219ACFGILMPSTVYdi} is an unusual mutation at this position.
|
|
K219N/R occur commonly in heavily NRTI-treated patients. Their effect on NRTI susceptibility is uncertain.
|
|
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.
|
|
K219W/H/D are uncommon NRTI-selected mutations at this position.
|
|
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.
|
|
H221Y is an uncommon NNRTI-associated mutation. Its phenotypic effect on current NNRTIs has not been studied.
|
|
P225H increases EFV resistance when present in combination with K103N. $listMutsIn{225ACDEFGIKLMNQRSTVWYdi} is a highly unusual mutation at this position.
|
|
P225H increases EFV resistance when present in combination with K103N.
|
|
F227LC are NNRTI-associated mutations. $listMutsIn{F227ADEGHIKMNPQRSTVWYdi} is a highly unusual mutation at this position.
|
|
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.
|
|
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.
|
|
M230L causes intermediate-to-high-level resistance to each of the NNRTIs. $listMutsIn{230ACDEFGHIKNPQRSTVWYdi} is a highly unusual mutation at this position.
|
|
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.
|
|
L234I is an uncommon NNRTI associated mutation. $listMutsIn{234ACDEFGHKMNPQRSTVWYdi} is a highly unusual mutation at this position.
|
|
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.
|
|
P236L causes high-level DLV resistance. $listMutsIn{236ACDEFGHIKMNQRSTVWYdi} is a highly unusual mutation at this position.
|
|
P236L causes high-level DLV resistance.
|
|
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.
|
|
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.
|
|
K238R is a naturally occurring variant that is common in some non-B subtypes and does not reduce NNRTI susceptibility.
|
|
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.
|
|
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.
|
|
Y318F is an uncommon mutation that causes high-level DLV resistance and low/intermediate NVP resistance.
|
|
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.
|
|
N348I causes low-level reductions in AZT and NVP susceptibility. $listMutsIn{348ACDEFGHKLMPQRSTVWYdi} is an unusual mutation at this position.
|
|
N348I causes low-level reductions in AZT and NVP susceptibility.
|