HIVdb version 8.1.1 (last updated 2016-09-23)

NNRTI Resistance Mutation Comments

(PI · NRTI · INSTI)
MutationTypeComment
V90IOtherV90I is a polymorphic accessory mutation weakly selected by each of the NNRTIs. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score but is associated with minimal, if any, detectable reduction in NNRTI susceptibility.
A98GNNRTIA98G is a non-polymorphic accessory mutation associated with low-level reduced susceptibility to each of the NNRTIs.
L100INNRTIL100I is a non-polymorphic mutation that usually occurs in combination with K103N. In this setting it causes high-level resistance to NVP, EFV, and RPV and intermediate resistance to ETR. It has a weight of 2.5 in the Tibotec ETR genotypic susceptibility score.
L100VNNRTIL100I is a non-polymorphic mutation that usually occurs with K103N. In this setting it causes high-level resistance to NVP, EFV, and RPV and intermediate resistance to ETR. L100V is a rare non-polymorphic mutation with low / intermediate resistance to EFV, NVP, and RPV.
K101ENNRTIK101E is a non-polymorphic primarily accessory mutation that causes intermediate resistance to NVP and RPV, low-level resistance to EFV, and potentially low-level resistance to ETR. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score.
K101HNNRTIK101H is a non-polymorphic accessory mutation selected by NVP, EFV and ETR. When present with other NNRTI-resistance mutations, K101H further reduces susceptibility to these NNRTIs. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score.
K101NATOtherK101N/A/T are uncommon non-polymorphic NNRTI-selected mutation of uncertain phenotypic and clinical significance.
K101PNNRTIK101P is a non-polymorphic mutation that causes high-level resistance to each of the NNRTIs. It has a weight of 2.5 in the Tibotec ETR genotypic susceptibility score.
K101QOtherK101Q is a relatively non-polymorphic mutation that is weakly selected in patients receiving NVP and EFV. It is of uncertain phenotypic and clinical significance.
K103EQNNRTIK103E/Q are rare mutations that have not been associated with reduced NNRTI susceptibility.
K103HNNRTIK103H is a rare non-polymorphic mutation that causes high-level resistance to NVP and EFV.
K103NNNRTIK103N is a non-polymorphic mutation that causes high-level resistance to NVP and EFV.
K103ROtherK103R is a polymorphic mutation that alone has no effect on NNRTI susceptibility. However, in combination with V179D, it reduces NVP and EFV susceptibility about 15-fold.
K103SNNRTIK103S is a non-polymorphic mutation that causes high-level resistance to NVP and intermediate resistance to EFV. Because K103S is a 2-bp change from the wildtype K and a 1-bp change from K103N, patients with K103S may be likely to have once had K103N.
K103TNNRTIK103T is an extremely rare non-polymorphic mutation that appears to cause intermediate/high-level resistance to NVP. It has little if any effect on EFV susceptibility.
V106ANNRTIV106A is a non-polymorphic mutation that causes high-level resistance to NVP and intermediate resistance to EFV.
V106IOtherV106I is a polymorphic NNRTI-selected accessory mutation. It has a weight of 1.5 in the Tibotec ETR genotypic susceptibility score. It has minimal, if any, effect on NNRTI susceptibility.
V106MNNRTIV106M is a non-polymorphic mutation that causes high-level resistance to NVP and EFV.
V108INNRTIV108I is a relatively non-polymorphic accessory mutation selected in patients receiving NVP, EFV and ETR. It causes low-level resistance to NVP and potentially low-level resistance to EFV. It does not appear to reduce susceptibility to ETR or RPV.
I132MLOtherI132M is an extremely rare non-polymorphic mutation associated with uncertain amount of reduced NVP and EFV susceptibility. I132L is a more common, non-polymorphic NNRTI-selected mutation that has not been well studied.
E138ANNRTIE138A is a common polymorphic accessory mutation weakly selected in patients receiving ETR and RPV. It reduces ETR and RPV susceptibility ~2-fold. It has a weight of 1.5 in the Tibotec ETR genotypic susceptibility score.
E138KNNRTIE138K is a non-polymorphic mutation selected in a high proportion of patients receiving RPV. It reduces RPV susceptibility by 2 to 3-fold and in combination with K101E or the NRTI-resistance mutation M184I, it is sufficient to cause virological failure on a first-line RPV-containing regimen. E138K causes low-level cross-resistance to ETR but minimal, if any, cross-resistance to NVP and EFV.
E138QGNNRTIE138Q/G are non-polymorphic accessory mutations frequently selected in patients receiving ETR and RPV and occasionally in patients receiving NVP and EFV. Preliminary data suggest that E138Q/G are associated with 2 to 3-fold reduced susceptibility to each of the NNRTIs.
E138RNNRTIE138R is a rare non-polymorphic accessory mutation selected in vitro by RPV. It is associated with 2 to 3-fold reduced susceptibility to ETR and RPV.
V179DENNRTIV179D is a polymorphic accessory NNRTI-selected mutation. It contributes low-levels reductions in susceptibility to each of the NNRTIs. The combination of V179D and K103R act synergistically to reduce NVP and EFV susceptibility ~10-fold. V179D has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score. V179E is a non-polymorphic mutation occasionally selected by NVP and EFV. V179E appears similar to V179D in its effects on NNRTIs. V179D/E do not appear to reduce the virological response to a first-line EFV-containing regimen.
V179FNNRTIV179F is a non-polymorphic mutation frequently selected in patients receiving ETR. It nearly always occurs in combination with Y181C. Alone V179F has little effect on NNRTI susceptibility. In combination with Y181C, however, it is associated with high-level ETR and RPV resistance. It has a weight of 1.5 in the Tibotec ETR genotypic susceptibility score.
V179IOtherV179I is a polymorphic mutation that is frequently selected in patients receiving ETR and RPV. But It has little, if any, direct effect on NNRTI susceptibility.
V179LNNRTIV179L is a rare non-polymorphic mutation occasionally selected in patients receiving NNRTIs. Its effects on NNRTI susceptibility have not been well studied. It is listed as an RPV-associated resistance mutation in the RPV package-insert.
V179TNNRTIV179T is a relatively rare non-polymorphic mutation occasionally selected in patients receiving NNRTIs. It is associated with minimal, if any, reduction in ETR and RPV susceptibility. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score.
Y181CNNRTIY181C is a non-polymorphic mutation selected in patients receiving NVP, ETR and RPV. It reduces susceptibility to NVP, ETR, RPV, and EFV by >50-fold, 5-fold, 3-fold, and 2-fold, respectively. Although Y181C itself reduces EFV susceptibility by only 2-fold, it has been associated with a reduced response to an EFV-containing regimen in NNRTI-experienced patients. Y181C has a weight of 2.5 in the Tibotec ETR genotypic susceptibility score.
Y181FSGNNRTIY181F/S/G are rare non-polymorphic NNRTI-associated mutations that are usually present as part of an electrophoretic mixture. They are likely to represent transitional mutations between Y and I or V.
Y181IVNNRTIY181I/V are 2-base pair non-polymorphic mutations selected by NVP and ETR. They cause high-level resistance to NVP, ETR, and RPV. They each have a weight of 3.0 in the Tibotec ETR genotypic susceptibility score.
Y188CNNRTIY188C is a non-polymorphic mutation selected in patients receiving NVP and EFV. It confers high-level resistance to NVP and EFV.
Y188FNNRTIY188F is a rare non-polymorphic NNRTI-associated mutation that is usually present as part of an electrophoretic mixture. It appears to represent a transitional mutation between Y and L.
Y188HNNRTIY188H is a non-polymorphic mutation selected in patients receiving NVP and EFV. It causes about 5 to 10-fold reduced susceptibility to NVP and EFV.
Y188LNNRTIY188L is a non-polymorphic mutation that causes high-level resistance to NVP, EFV, and RPV and potentially low-level resistance to ETR.
G190ANNRTIG190A is a non-polymorphic mutation that causes high-level resistance to NVP and intermediate resistance to EFV. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score but does not appear to be selected by ETR or RPV or to reduce their in vitro susceptibility in the absence of other NNRTI-resistance mutations.
G190CTVNNRTIG190C/T/V are rare non-polymorphic mutations that cause high-level resistance to NVP and EFV. Their effects on ETR and RPV susceptibility are not known.
G190EQNNRTIG190E is a non-polymorphic mutation that causes high-level resistance to each of the NNRTIs. G190Q is a less common non-polymorphic NNRTI-selected mutation that is associated with high-level NVP and EFV resistance and probable intermediate / high-level resistance to ETR and RPV.
G190SNNRTIG190S is a non-polymorphic mutation that causes high-level resistance to NVP and EFV. It has a weight of 1.5 in the Tibotec ETR genotypic susceptibility score but does not appear to be selected by ETR or RPV or to reduce their in vitro susceptibility in the absence of other NNRTI-resistance mutations.
H221YNNRTIH221Y is a non-polymorphic accessory mutation selected primarily by NVP and RPV. It frequently occurs in combination with Y181C.
P225HNNRTIP225H is a non-polymorphic EFV-selected mutation that usually occurs in combination with K103N. The combination of P225H and K103N synergistically reduces EFV susceptibility.
F227CNNRTIF227C is an extremely rare non-polymorphic mutation selected by ETR and RPV. It usually occurs in combination with other NNRTI-resistance mutations and in this context it is associated with high-level resistance to each of the NNRTIs.
F227LNNRTIF227L is a non-polymorphic mutation that usually occurs in combination with V106A. In this context it is associated with high-level resistance to NVP and EFV.
M230INNRTIM230I is an extremely rare mutation selected by RPV. Its effects on NNRTI susceptibility have not been well studied. It also often occurs as a result of APOBEC-mediated G-to-A hypermutation resulting in viruses that are likely to be noninfectious.
M230LNNRTIM230L is an uncommon non-polymorphic mutation selected in patients receiving EFV, NVP, and RPV. It causes intermediate to high-level resistance to each of the NNRTIs.
P236LNNRTIP236L is a non-polymorphic mutation that causes high-level DLV resistance but does not reduce susceptibility to any other NNRTIs.
K238ROtherK238R is a common polymorphism that does not reduce NNRTI susceptibility.
K238TNNNRTIK238T is a non-polymorphic mutation selected in patients receiving NVP and EFV. It usually occurs in combination with K103N. It reduces susceptibility to NVP and EFV by about 5-fold. It may also reduce susceptibility to ETR and RPV. K238N is a non-polymorphic accessory mutation that is also selected by NVP and EFV. It appears to have minimal, if any, effects on NNRTI susceptibility.
Y318FNNRTIY318F is an uncommon mutation that causes intermediate NVP resistance and potentially low-level EFV resistance.
N348INNRTIN348I is a non-polymorphic accessory mutation selected by NVP and EFV and the NRTIs AZT and D4T. Alone it reduces AZT and NVP susceptibility by about 3-fold and EFV susceptibility by 2-fold.