Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

NNRTI Resistance Notes

Last updated on Feb 28, 2014
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90VIV90I is a polymorphic accessory mutation that is weakly selected in patients 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.
98AGA98G is a nonpolymorphic accessory mutation that reduces NVP susceptibility by ~5-fold and EFV susceptibility by about 3-fold. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score.
100LIL100I is a nonpolymorphic mutation that usually occurs in combination with K103N. In this setting it causes high-level resistance to NVP and EFV (>50-fold reduced susceptibility), high-level resistance to RPV (>10-fold reduced susceptibility) and intermediate-level resistance to ETR (~5-fold reduced susceptibility). It has a weight of 2.5 in the Tibotec ETR genotypic susceptibility score.
100LVL100V is an extremely rare nonpolymorphic mutation associated with 5 to 10-fold reduced susceptibility to NVP and EFV. It may also reduce susceptibility to ETR and RPV.
101KEK101E is a nonpolymorphic mutation that causes intermediate resistance to NVP (~5-fold reduced susceptibility) and low-level resistance (~2-fold reduced susceptibility) to EFV, ETR and RPV. It has a weight of 1.0 in the Tibotec ETR genotypic susceptibility score. In combination with M184I it reduces RPV susceptibility by about 5-fold.
101KHK101H is a nonpolymorphic accessory NNRTI-resistance 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.
101KNK101N/A/T are uncommon nonpolymorphic NNRTI-selected mutation of uncertain phenotypic and clinical significance.
101KPK101P is a nonpolymorphic mutation that causes high-level resistance (>50-fold reduced susceptibility) to NVP, EFV and RPV and intermediate resistance (~5-fold reduced susceptibility) to ETR. It has a weight of 2.5 in the Tibotec ETR genotypic susceptibility score.
101KQK101Q is a relatively nonpolymorphic mutation that is weakly selected in patients receiving NVP and EFV. It is of uncertain phenotypic and clinical significance.
101KRK101R is an uncommon polymorphism that is not associated with reduced NNRTI susceptibility.
103KEQK103E/Q are rare mutations that have not been associated with reduced susceptibility to the current NNRTIs.
103KHK103H is a rare nonpolymorphic mutation that causes high-level resistance (~20-fold reduction in susceptibility) to NVP and EFV.
103KNK103N is a nonpolymorphic mutation that causes high-level resistance to NVP (~50-fold reduced susceptibility) and EFV (~20-fold reduced susceptibility).
103KRK103R is a polymorphic mutation that by alone has no effect on NNRTI susceptibility. However, in combination with V179D (and possibly V179E), it reduces NVP and EFV susceptibility about 15-fold.
103KSK103S is a nonpolymorphic mutation that causes intermediate/high-level resistance to NVP and low/intermediate-level resistance to EFV. Because K103S is a 2-bp change from the wildtype K, patients with K103S may be more likely to harbor K103N (which is just a 1-bp change from wildtype).
103KTK103T is an extremely rare nonpolymorphic mutation that appears to cause intermediate/high-level resistance to NVP (~10-fold reduction in susceptibility), but it has little if any effect on EFV susceptibility.
106VAV106A is a nonpolymorphic mutation that causes high-level resistance to NVP (~50-fold reduced susceptibility) and intermediate-level resistance to EFV (~5-fold reduction in susceptibility). Together, V106A and F227L cause high-level resistance to both NVP and EFV.
106VIV106I 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.
106VMV106M is a nonpolymorphic mutation that causes high-level resistance (>30-fold reduced susceptibility) to NVP and EFV.
108VIV108I is a relatively nonpolymorphic accessory mutation selected in patients receiving NVP, EFV and ETR. It causes low-level resistance (~2-fold reduction in susceptibility) to NVP and EFV. It does not appear to reduce susceptibility to ETR or RPV.
138EAE138A 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.
138EGQE138Q/G are nonpolymorphic accessory mutations frequently selected in patients receiving ETR and RPV and occasionally in patients receiving NVP and EFV. E138Q/G are associated with 2 to 3-fold reduced susceptibility to ETR and RPV.
138EKE138K is a nonpolymorphic mutation selected in a high proportion of patients receiving RPV. Alone it causes low-level RPV resistance (2 to 3-fold reduced susceptibility). However, in combination with the NRTI-resistance mutation M184I it appears sufficient to cause virological failure on an RPV-containing regimen. E138K causes low-level cross-resistance to ETR but minimal, if any, cross-resistance to NVP and EFV.
138ERE138R is a rare nonpolymorphic accessory mutation selected in vitro by RPV. It is associated with 2 to 3-fold reduced susceptibility to ETR and RPV.
179VDEV179D is a polymorphic accessory mutation selected in patients receiving EFV. It reduces NVP and EFV susceptibility by 2 to 5-fold and ETR and RPV susceptibility ~2-fold. 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 GSS. V179E is a nonpolymorphic mutation infrequently selected by NVP and EFV. V179E appears to be similar to V179D in its effects on NNRTIs.
179VFV179F is a nonpolymorphic 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 (>10-fold reduced susceptibility). It has a weight of 1.5 in the Tibotec ETR GSS.
179VIV179I is a polymorphic mutation that is frequently selected in patients receiving ETR and RPV. It has little, if any, effect on NNRTI susceptibility.
179VLV179L is a rare nonpolymorphic mutation infrequently selected in patients receiving NVP, EFV and RPV. Its effects on NNRTI susceptibility have not been well studied. It is listed as an RPV-associated drug-resistance mutation in the RPV package insert.
179VTV179T is a rare nonpolymorphic mutation infrequently selected in patients receiving NNRTIs. It is associated with minimal reductions in ETR and RPV susceptibility. It has a weight of 1.0 in the Tibotec ETR GSS.
181YCY181C is a nonpolymorphic 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 is associated with a reduced response to an EFV-containing regimen because viruses with this mutation often harbor additional minority variant NNRTI-resistance mutations. Y181C has a weight of 2.5 in the Tibotec ETR GSS.
181YFSGY181F/S/G are rare nonpolymorphic 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.
181YIVY181I/V are 2-base pair nonpolymorphic mutations selected by NVP and ETR. Y181I/V cause high-level resistance to NVP (>50-fold reduced susceptibility) and to ETR and RVP (10 to 15-fold reduced susceptibility). Y181I/V each have a weight of 3.0 in the Tibotec ETR genotypic susceptibility score.
188YCY188C is a nonpolymorphic mutation selected in patients receiving NVP and EFV. It confers high-level resistance to NVP (>50-fold reduced susceptibility) and EFV (~20-fold reduced susceptibility).
188YFY188F is a rare nonpolymorphic NNRTI-associated mutations that is usually present as part of an electrophoretic mixture. It appears to represent a transitional mutation between Y and L.
188YHY188H is a nonpolymorphic mutation selected in patients receiving NVP and EFV. It causes about 5 to 10-fold reduced susceptibility to NVP and EFV.
188YLY188L is a nonpolymorphic mutation that causes high-level resistance (>50-fold reduced susceptibility) to NVP and EFV and intermediate/high-level resistance (5-fold reduced susceptibility) to RPV.
190GAG190A is a nonpolymorphic mutation that causes high-level resistance to NVP (>50-fold reduced susceptibility) and intermediate resistance to EFV (5 to 10-fold reduced susceptibility). It has a weight of 1.0 in the Tibotec ETR GSS but does not appear to be selected by ETR or RPV or to reduce their in vitro susceptibility.
190GCTVG190C/T/V are rare nonpolymorphic mutations that cause high-level resistance to NVP and EFV (>50-fold reduced susceptibility). Their effects on ETR and RPV susceptibility are not known.
190GEQG190E/Q are nonpolymorphic mutations that cause high-level resistance to NVP and EFV (>50-fold reduced susceptibility). Both mutations also appear to be associated with high-level resistance (>10-fold reduced susceptibility) to RPV and ETR.
190GSG190S is a nonpolymorphic mutation that causes high-level resistance to NVP and EFV (>50-fold reduced susceptibility). 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.
221HYH221Y is a nonpolymorphic accessory NNRTI-selected mutation that frequently occurs in combination with Y181C. Alone it has minimal detectable effects on NNRTI susceptibility. It is frequently selected in patients receiving RPV (Rimsky 2012, Tibotec 2012).
225PHP225H is a nonpolymorphic EFV-selected mutation that usually occurs in combination with K103N. The combination of P225H and K103N causes a >50-fold reduction in EFV susceptibility.
227FCF227C is an extremely rare nonpolymorphic mutation selected in patients receiving RPV and in vitro 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.
227FLF227L is a nonpolymorphic mutation that usually occurs in combination with V106A. In this setting it is associated with high-level resistance to NVP and EFV.
230MIM230I is an extremely rare mutation selected in vitro by RPV. Its effects on NNRTI susceptibility have not been well studied.
230MLM230L is an uncommon nonpolymorphic mutation selected in patients receiving EFV, NVP, and RPV. It causes intermediate to high-level resistance to each of the NNRTIs.
236PLP236L is a nonpolymorphic mutation that causes high-level DLV resistance but does not reduce susceptibility to any other NNRTIs.
238KRK238R is a common polymorphism that does not reduce NNRTI susceptibility.
238KTNK238T is a nonpolymorphic 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 nonpolymorphic accessory mutation that is also selected by NVP and EFV. It appears to have minimal, if any, effects on NNRTI susceptibility.
318YFY318F is an uncommon mutation that causes intermediate-level NVP resistance and potentially low-level EFV resistance.
348NIN348I is a nonpolymorphic accessory mutation selected by the NRTIs AZT and d4T and by NVP and EFV. Alone it reduces AZT and NVP susceptibility by about 3-fold and EFV susceptibility by 2-fold.