Resistance Matrix

Resistance Mutation Comments

Resistance Mutation Scores

Drug Summaries

Position	Cons	AA	Comment
98	A	G	A98G reduces NVP and EFV susceptibility by about 5-fold and 3-fold, respectively. In combination with other mutations it is associated with reduced ETR and RPV susceptibility.
98	A	S	A98S is a common polymorphism that does not reduce NNRTI susceptibility.
100	L	I	L100I usually occurs in combination with K103N and in this setting it causes high-level NVP and EFV resistance and intermediate ETR and RPV resistance (>5-fold decreased susceptibility).
101	K	E	K101E causes intermediate resistance to NVP (5 to 10-fold decreased susceptibility) and low-level resistance to EFV, ETR, and RPV (2 to 5-fold).
101	K	HN	K101H/N are uncommon NNRTI-associated mutations. K101H has been associated with low-level decreased NVP, EFV, and ETR susceptibility when present with other NNRTI-resistance mutations.
101	K	P	K101P causes high-level (>50-fold decreased susceptibility) to NVP, EFV, and RPV and intermediate resistance to ETR (>5-fold).
101	K	Q	K101Q is a relatively nonpolymorphic mutation that occurs slightly more commonly in patients receiving NNRTIs. It may contribute to reduced NVP, EFV, and ETR susceptibility when present with other NNRTI-resistance mutations.
101	K	R	K101R is an uncommon polymorphism that is not associated with decreased NNRTI susceptibility.
103	K	EQ	K103E/Q are rare mutations that have not been associated with resistance to the current NNRTIs.
103	K	H	K103H is a rare mutation that is associated with 10 to 20-fold decreased susceptibility to NVP and EFV
103	K	N	K103N causes high-level resistance to NVP, and EFV. it has no effect on ETR or RPV susceptibility.
103	K	R	K103R is a polymorphic mutation that by itself has no effect on NNRTI susceptibility. However, in combination with V179D it reduces NVP and EFV susceptibility >10-fold.
103	K	S	K103S causes intermediate/high-level resistance to NVP (>10-fold decreased susceptibility) and low/intermediate-level resistance to EFV (~5-fold). 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.
103	K	T	K103T is a rare mutation that appear to be associated with >10-fold decreased NVP susceptibility but no effect on other NNRTIs.
106	V	A	V106A causes high-level resistance to NVP and low-level resistance to EFV.
106	V	I	V106I is a common polymorphism. It is synergistic with V179D at reducing NVP, EFV, and possibly ETR susceptibility.
106	V	M	V106M causes high-level resistance to NVP and EFV.
108	V	I	V108I reduces NVP and EFV susceptibility about 2-fold.
138	E	A	E138A is a polymorphism that may contribute to reduced ETR and RPV susceptibility in combination with other NNRTI-resistance mutations.
138	E	GQR	E138G/Q/R are nonpolymorphic mutations that emerge during ETR therapy and reduce ETR and RPV susceptibility by ~2-3 fold. The effect of these mutations on NVP and EFV have not been well characterized.
138	E	K	E138K is a nonpolymorphic mutation that is selected commonly by RPV. By itself it reduces RPV susceptibility ~3-fold; in combination with the NRTI-resistance mutation M184I it reduces RPV susceptibility 6 to 7-fold. The combination of E138K + M184I alone is commonly found in patients with virological failure on an RPV-containing regimen. E138K causes low-level cross-resistance to ETR.
179	V	DE	V179D/E occur in ~1% of NNRTI-naive individuals and alone reduce NVP and EFV susceptibility ~2-fold. The combination of K103R + V179D reduces susceptibility to NVP and EFV ~10-fold. V179D contributes to reduced ETR susceptibility in combination with other mutations.
179	V	F	V179F nearly always occurs in combination with Y181C and is frequently selected for by ETR. By itself, V179F has no effect on ETR susceptibility but in combination with Y181C, it causes high-level ETR resistance.
179	V	I	V179I is a common polymorphism is often selected by ETR and RPV salvage therapy. It has not been shown to reduce NNRTI susceptibility.
179	V	T	V179T is a rare mutation that may contribute to reduced ETR susceptibility in combination with other mutations.
181	Y	C	Y181C causes high-level resistance to NVP, ~2-fold decreased susceptibility to EFV, and ~5-fold decreased susceptibility to ETR and RPV. Although Y181C reduces EFV susceptibility just 2-fold, older salvage therapy studies found that EFV was only transiently active in treating patients developing this mutation while receiving NVP.
181	Y	IV	Y181I/V cause high-level NVP resistance and 10 to 15-fold decreased ETR and RPV susceptibility.
188	Y	CH	Y188C causes high/intermediate resistance to NVP and low-level resistance to EFV.
188	Y	L	Y188L causes high-level resistance to NVP, EFV, and RPV. It does not appear to reduce ETR susceptibility.
190	G	A	G190A causes high level resistance to NVP and intermediate resistance to EFV. By itself, it does not decrease ETR susceptibility. However, it is synergistic with Y181C at reducing ETR susceptibility.
190	G	CTV	G190C/T/V are rare mutations that cause high-level resistance to NVP and EFV. Their effects on ETR and RPV are not known.
190	G	EQ	G190E/Q cause high-level resistance to NVP and EFV and are synergistic with Y181C at reducing ETR susceptibility.
190	G	S	G190S causes high-level resistance to NVP and EFV. However, it is synergistic with Y181C at reducing ETR susceptibility.
225	P	H	P225H increases EFV resistance in combination with K103N.
227	F	C	F227C is an extremely rare mutation which emerges in vitro with 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 all NNRTIs.
227	F	L	F227L usually occurs in combination with V106A and in this setting is associated with high level resistance to NVP and intermediate resistance to EFV. It does not appear to decrease ETR susceptibility.
230	M	L	M230L causes intermediate/high-level resistance to each of the NNRTIs. It has been selected in vitro by ETR and reduces ETR susceptibility by ~3 to 10-fold. M230L is selected by RPV in vitro and in vivo but its effect on RPV susceptibility has not yet been reported.
236	P	L	P236L causes high-level DLV resistance but does not decrease the susceptibility of any other NNRTIs.
238	K	R	K238R is a common polymorphism that does not reduce NNRTI susceptibility.
238	K	TN	K238T/N are NNRTI-selected mutations that usually occur in combination with K103N. In combination with K103N, it causes high-level resistance to NVP and EFV. Its effects on ETR and RPV are not well-studied. K238N occurs less commonly than K238T and appears to have a less effect than K238T on EFV and NVP susceptibility.
318	Y	F	Y318F is an uncommon mutation that causes intermediate-level NVP resistance and potentially low-level EFV resistance.
348	N	I	By itself, N348I causes about 3-fold reduced NVP susceptibility, 2-fold reduced EFV susceptibility, and 2-fold reduced AZT susceptibility. In combination with other NNRTI-resistance mutations or the rare mutation T369I, higher levels of NVP and EFV resistance have been reported.

There is an additional comment conditional on several mutations

DrugName	Comment
ETR	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).

$numberOfMutsIn{<list of mutations>} is replaced with the count of mutations present in the sequence and $listMutsIn{<list of mutations>} is replaced with the list of mutations present in the sequence.
For example, a sequence with 98G, 100I, and 106I would have an ETR comment that reads like "The following 3 of the 13 etravirine DUET study mutations were present: V98G, 100I, 106I (Katlama C et al, IAS 2007)."