HIVdb version 8.7 (last updated on 2018-10-19)

NNRTI Resistance Comments

(PI · NRTI · NNRTI · INSTI)
ConditionComment/
Mutation Type
Comment
90IOtherV90I 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.
98GNNRTIA98G is a non-polymorphic accessory mutation associated with low-level reduced susceptibility to each of the NNRTIs.
100INNRTIL100I 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. Preliminary data suggests it is contributes low to intermediate reductions in DOR susceptibility when it occurs in combination with K103N.
100VNNRTIL100I 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.
101ENNRTIK101E 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. It is associated with low-level reductions in DOR susceptibility.
101HNNRTIK101H 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. Its effect on DOR susceptibility is not known.
101NATOtherK101N/A/T are uncommon non-polymorphic NNRTI-selected mutation of uncertain phenotypic and clinical significance.
101PNNRTIK101P 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. Its does not appear to reduce DOR susceptibility.
101QOtherK101Q is a relatively non-polymorphic mutation that is weakly selected in patients receiving NVP and EFV. It is of uncertain phenotypic and clinical significance.
103EQNNRTIK103E/Q are rare mutations that have not been associated with reduced NNRTI susceptibility.
103HNNRTIK103H is a rare non-polymorphic mutation that causes high-level resistance to NVP and EFV.
103NNNRTIK103N is a non-polymorphic mutation that causes high-level reductions in NVP and EFV susceptibility.
103ROtherK103R 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.
103SNNRTIK103S is a non-polymorphic mutation that causes high-level reductions in NVP susceptibility but intermediate reductions in EFV susceptibility. Because K103S is a 2-bp change from the wildtype K and a 1-bp change from K103N, persons with K103S may be likely to have once had K103N.
103TNNRTIK103T 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.
106ANNRTIV106A is a non-polymorphic mutation that causes high-level resistance to NVP and intermediate resistance to EFV. It is selected in vitro and in vivo by DOR and alone it causes intermediate reductions in DOR susceptibility. In combination with other DOR-associated DRMs it is associated with high-level DOR resistance.
106IOtherV106I is occurs in 1% to 2% of viruses from untreated persons. It contributes to reduced NNRTI susceptibility in combination with other mutations. It has a weight of 1.5 in the Tibotec ETR genotypic susceptibility score despite not contributing much to reduced ETR susceptibility. It likely plays a greater role in reducing DOR susceptibility, particularly in combination with other NNRTI-associated DRMs.
106MNNRTIV106M is a non-polymorphic mutation that causes high-level resistance to NVP and EFV. It is selected in vitro and in vivo by DOR and preliminary data suggests it is associated with low/intermediate reductions in DOR susceptibility.
108INNRTIV108I is a relatively non-polymorphic accessory mutation selected in vitro and/or in vivo with each of the NNRTIs. It causes low-level reductions in susceptibility to NVP and DOR. Alone, it does not appear to reduce susceptibility to EFV, ETR, or RPV.
132MLOtherI132M 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.
138ANNRTIE138A 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.
138KNNRTIE138K 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 no cross-resistance to NVP, EFV, or DOR.
138QGNNRTIE138Q/G are non-polymorphic accessory mutations frequently selected in patients receiving ETR and RPV and occasionally in patients receiving NVP and EFV. In most studies, they cause low-level reductions in susceptibility to NVP, RPV, and ETR.
138RNNRTIE138R 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.
179DENNRTIV179D 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. 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.
179FNNRTIV179F 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.
179IOtherV179I 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.
179LNNRTIV179L 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.
179TNNRTIV179T 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.
181CNNRTIY181C 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. Alone, it does not appear to reduce DOR susceptibility.
181FSGNNRTIY181F/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.
181IVNNRTIY181I/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. Their effects on DOR have not been well-characterized.
188CNNRTIY188C is a non-polymorphic mutation selected in patients receiving NVP and EFV. It confers high-level resistance to NVP and EFV.
188FNNRTIY188F 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.
188HNNRTIY188H 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.
188LNNRTIY188L is a non-polymorphic mutation that causes high-level resistance to NVP, EFV, RPV, and DOR, and potentially low-level resistance to ETR.
190ANNRTIG190A 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. It also does not appear to reduce DOR susceptibility.
190CTVNNRTIG190C/T/V are rare non-polymorphic mutations that cause high-level resistance to NVP and EFV. Their effects on ETR, RPV, and DOR susceptibility are not known.
190EQNNRTIG190E is a non-polymorphic mutation that causes high-level resistance to each of the NNRTIs including DOR. G190Q is a less common non-polymorphic NNRTI-selected mutation that is associated with high-level NVP and EFV resistance. Its effects on RPV, ETR, and DOR susceptibility is not known.
190ROtherG190R is strongly suspicious for being an artifact of APOBEC-mediated G-to-A hypermutation. It has not been associated with reduced NNRTI susceptibility.
190SNNRTIG190S 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. Preliminary data suggests it is associated with low/intermediate reductions in DOR susceptibility.
221YNNRTIH221Y is a non-polymorphic accessory mutation selected primarily by NVP and RPV. It frequently occurs in combination with Y181C.
225HNNRTIP225H is a non-polymorphic EFV-selected mutation that usually occurs in combination with K103N. The combination of P225H and K103N synergistically reduces NVP, EFV and DOR susceptibility.
227CNNRTIF227C is a nonpolymorphic mutation selected in persons receiving DOR and rarely in persons receiving ETR and RPV. It usually occurs in combination with other DRMs and in this setting has consistently been associated with the highest possible levels of DOR resistance. It is also usually associated with intermediate or higher reductions in susceptibility to NVP, EFV, ETR, and RPV.
227ILVNNRTIF227L is a non-polymorphic mutation that usually occurs in combination with V106A. It is selected in vivo and in vitro with both NVP and DOR. In this context it is associated with high-level reductions in NVP and DOR susceptibility and intermediate reductions in EFV susceptibility. F227I/V are extremely rare mutations that have been selected in vitro by DOR.
230INNRTIM230I 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.
230LNNRTIM230L is an uncommon non-polymorphic mutation selected in persons receiving EFV, NVP, and RPV. It causes intermediate to high-level resistance to each of the NNRTIs.
234INNRTIL234I is a nonpolymorphic mutation selected in persons receiving NVP and EFV. It is also selected in vitro by ETR and DOR. In combination with V106A, it is associated with high-level DOR resistance. Its effect on susceptibility when it occurs alone has not been studied.
236LNNRTIP236L is a non-polymorphic mutation that causes high-level DLV resistance but does not reduce susceptibility to any other NNRTIs.
238ROtherK238R is a common polymorphism that does not reduce NNRTI susceptibility.
238TNNNRTIK238T 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.
318FNNRTIY318F is an uncommon mutation that causes intermediate NVP resistance and potentially low-level EFV resistance. It has been selected in vivo by DOR but its effect on DOR susceptibility has not been studied.
348INNRTIN348I 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.