Resistance Matrix

Resistance Mutation Comments

Resistance Mutation Scores

Drug Summaries

Position	Cons	AA	Comment
10	L	IVFRY	L10I/V/F/R/Y are associated with resistance to most PIs when present with other mutations. L10I/V occur in 5-10% of untreated persons. L10F is a non-polymorphic mutation which is associated with decreased susceptibility to all PIs except ATV/r, SQV/r, and TPV/r. L10R/Y are rare poorly characterized mutations.
11	V	IL	V11IL are PI-selected mutation that are weakly associated with decreased FPV/r and DRV/r susceptibility.
20	K	RMITV	K20R/M/I/T/V are PI-selected mutations. K20R is highly polymorphic and probably makes the least contribution to decreased PI susceptibility. K20I/M/T/V are nonpolymorphic in most subtypes. They appear to be selected most commonly by NFV and to reduce its susceptibility.
23	L	I	L23I is a rare substrate cleft mutation that causes low-level NFV resistance.
24	L	F	L24I is associated with reduced susceptibility to IDV/r and LPV/r and possibly SQV/r, and ATV/r when present with other mutations. It increases TPV/r susceptibility. L24F is a rare mutation at this position; its phenotypic effect is not known.
24	L	I	L24I is associated with reduced susceptibility to IDV/r and LPV/r and possibly SQV/r, and ATV/r when present with other mutations. It increases TPV/r susceptibility.
30	D	N	D30N causes high-level resistance to NFV.
32	V	I	V32I is a substrate cleft mutation which is associated with reduced susceptibility to all PIs except SQV/r.
33	L	F	L33F is selected by FPV/r, DRV/r, LPV/r, ATV/r, and TPV/r, and contribute resistance to these drugs.
33	L	I	L33F is selected by FPV/r, DRV/r, LPV/r, ATV/r, and TPV/r, and contribute resistance to these drugs. L33I is less common than L33F but may have a similar effect.
33	L	V	L33V is a polymorphism that does not appear to be related to PI therapy or drug resistance.
35	E	G	E35G is a nonpolymorphic mutation that is selected by NFV and which is weakly associated with decreased TPV susceptibility.
36	M	ILTV	M36I is weakly associated with PI resistance in subtype B viruses when present with other mutations. However, M36I is the consensus amino acid in most non-B subtypes. M36L/V/T are uncommon mutations at this position of unknown significance.
43	K	T	K43T is a nonpolymorphic PI-selected accessory mutation that in combination with other mutations is associated with reduced susceptibility to most PIs. It is also part of the genotypic susceptibility score (GSS) for TPV/r.
46	M	IL	M46I/L decreases susceptibility to IDV/r, NFV, FPV/r, LPV/r, and ATV/r when present with other mutations.
46	M	V	M46I/L decreases susceptibility to IDV/r, NFV, FPV/r, LPV/r, and ATV/r when present with other mutations. M46V is an uncommon PI-selected mutation at this position.
47	I	A	I47A usually occurs with V32I and in this setting causes high-level LPV/r and FPV/r resistance and decreased DRV/r susceptibility.
47	I	V	I47V decrease susceptibility to FPV/r, ATV/r, IDV/r, LPV/r, TPV/r, and DRV/r.
48	G	ASTQL	G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance.G48M is a less common mutation that appears to have similar effects on ARV susceptibility. G48A/S/T/Q are rare PI-selected mutations.
48	G	M	G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance. G48M is a less common mutation that appears to have similar effects on ARV susceptibility.
48	G	V	G48V causes high-level SQV/r resistance, intermediate ATV/r and NFV resistance, and low-level IDV/r and LPV/r resistance.
50	I	L	I50L causes intermediate-to-high level resistance to ATV/r and increased susceptibility to the remaining PIs.
50	I	V	I50V causes intermediate-to-high-level resistance to FPV/r, low-intermediate resistance to LPV/r and DRV/r, and increased susceptibility to TPV/r.
53	F	LY	F53L is associated with decreased susceptibility to SQV/r and ATV/r. F53Y is a rare PI-selected variant at this position.
54	I	L	I54L occurs in patients receiving FPV/r, LPV/r, and DRV/r and reduces susceptibility to these PIs and to NFV and possibly ATV/r. It increases TPV/r susceptibility.
54	I	M	I54M is selected by FPV/r, LPV/r, and DRV/r and reduces susceptibility to each of the PIs.
54	I	TAS	I54T/A/S are PI-related mutations in combination with other mutations are associated with decreased susceptibility to each of the PIs. However, their effects have not been as well studied as I54V, I54M, or I54L.
54	I	V	I54V contributes resistance to each of the PIs except DRV/r. It is synergistic with V82A/S/T in decreasing PI susceptibility.
58	Q	E	Q58E is a nonpolymorphic PI-selected mutation associated with decreased susceptibility to TPV/r and possibly other PIs.
63	L	P	L63P is a common polymorphism that is also selected by PIs.
71	A	TVIL	A71T/V are polymorphisms that occur in 2-3% of untreated persons but which increase in frequency in persons receiving PIs. A71I/L are nonpolymorphic mutations that occur in viruses with multiple PI-resistance mutations.
73	G	STCA	G73S/T/C/A are selected by and appear to be associated with decreased susceptibility to most, if not all, PIs. Their effect on SQV/r and NFV and possibly ATV/r appears to be greater than their effect on other PIs.
74	T	P	T74P is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It has been associated with decreased virological response to TPV/r and to a lesser extent DRV/r. It is probably associated with decreased susceptibility to multiple PIs.
74	T	S	T74S is associated with reduced NFV susceptibility. It occurs in about 5% of untreated persons with subtype C viruses.
76	L	V	L76V reduces susceptibility to FPV/r, IDV/r, LPV/r, and DRV/r and increases susceptibility to SQV/r, ATV/r, and TPV/r.
77	V	I	V77I is a common polymorphism that is selected by NFV.
82	V	A	V82A reduces susceptibility to IDV/r and LPV/r. With other mutations it is associated with reduced susceptibility to NFV, ATV/r, SQV/r, and FPV/r.
82	V	C	V82C is a rare mutation that occurs primarily in protease genes containing multiple other PI-resistance mutations.
82	V	F	V82F reduces susceptibility to IDV/r, LPV/r, FPV/r, DRV/r, and NFV.
82	V	I	V82I is a polymorphism that is common in some non-B subtypes; it has little if any effect on PI susceptibility.
82	V	L	V82L is a rare TPV/r-selected mutation which decreases TPV/r susceptibility. Its effect on other PIs has not been characterized.
82	V	M	V82M reduces IDV/r, LPV/r susceptibility in subtype G viruses. Its effect on other PIs has not been studied.
82	V	S	V82S probably has a similar effect to V82T which reduces susceptibility to IDV/r, LPV/r, and TPV/r and with other mutations is associated with reduced susceptibility to NFV, ATV/r, FPV/r, and SQV/r.
82	V	T	V82T reduces susceptibility to IDV/r, LPV/r, and TPV/r. With other mutations it is associated with reduced susceptibility to NFV and ATV/r.
83	N	D	N83D is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It is associated with a decreased virological response to TPV/r and probably contributes decreased susceptibility to other PIs.
84	I	AC	I84V causes intermediate/high-level resistance to ATV/r, FPV/r, IDV/r, NFV, and SQV/r; and low-level resistance to LPV/r, TPV/r, and DRV/r. I84A is an uncommon mutation that causes at least similar levels of resistance to each of the PIs. I84C is an even less common mutation that has not been well-characterized.
84	I	V	I84V causes intermediate/high-level resistance to ATV/r, FPV/r, IDV/r, NFV, and SQV/r; and low-level resistance to LPV/r, TPV/r, and DRV/r.
85	I	V	I85V is a nonpolymorphic PI-selected mutation.
88	N	D	N88D is selected by NFV. In combination with D30N, it synergistically reduces NFV susceptibility.
88	N	S	N88S causes high-level resistance to NFV and ATV/r and low-level resistance to IDV/r; it increases susceptibility to FPV/r.
88	N	TG	N88S causes high-level resistance to NFV and ATV/r and low-level resistance to IDV/r; it increases susceptibility to FPV/r. N88T/G are rare PI-selected mutations that have much less pronounced effects than N88S.
89	L	IT	L89T/I are non-polymorphic PI-selected mutation of uncertain phenotypic and clinical significance.
89	L	M	L89M is a common polymorphism that is not associated with decreased PI susceptibility.
89	L	V	L89V is a nonpolymorphic PI-selected accessory mutation which emerges commonly during treatment with DRV/r and in combination with other mutations is associated with decreased virological response to DRV/r salvage therapy.
90	L	M	L90M reduces susceptibility to NFV, SQV/r, ATV/r, and IDV/r. When present with other mutations it also reduces susceptibility to FPV/r and LPV/r.
93	I	L	I93L is a common polymorphism. It is the consensus residue in most subtypes. In subtype B, it is weakly associated with PI treatment.
93	I	M	I93M is a rare PI-associated mutation; its effect on PI susceptibility is not known.

There are 2 additional comments conditional on several mutations

DrugName	Comment
DRVr	The following $numberOfMutsIn{11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V} of the 11 darunavir/r POWER/DUET study mutations were present: $listMutsIn{11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V} (DeMeyer S et al, EHDRW 2008).
TPVr	This sequence has $numberOfMutsIn{47V,54AMV,58E,74P,82LT,83D} major TPV/r-resistance mutations ($listMutsIn{47V,54AMV,58E,74P,82LT,83D}), $numberOfMutsIn{10V,36I,43T,46L,84V} minor TPV/r-resistance mutations ($listMutsIn{10V,36I,43T,46L,84V}), and $numberOfMutsIn{24I,50LV,54L,76V} mutations associated with increased TPV/r responsiveness ($listMutsIn{24I,50LV,54L,76V}). RESIST study (Baxter J et al J Virology 2006 and Scherer J et al EACS 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 both 32I and 84V would have a DRV/r comment that reads like "The following 2 of the 11 darunavir/r POWER/DUET study mutations were present: 32I, 84V (DeMeyer S et al, EHDRW 2008)."