Algorithm Name: HIVDB
Algorithm Version: 4.3.7

NRTI

Position	AA	3TC	FTC	ABC	AZT	D4T	DDI	TDF
41	L	4	4	12	15	15	12	12
44	A	5	5	2	2	2	2	2
44	D	5	5	2	2	2	2	2
62	V	0	0	2	2	2	2	2
65	R	30	30	30	-5	15	30	40
65	N	15	15	10	0	0	15	15
67	-	15	15	25	30	30	25	15
67	E	0	0	5	10	10	5	0
67	G	0	0	8	15	12	8	5
67	N	0	0	8	15	12	8	5
67	S	0	0	5	5	5	5	5
67	T	0	0	5	5	5	5	5
67	H	0	0	5	5	5	5	5
69	-	15	15	25	30	30	25	15
69	A	2	2	2	2	2	5	2
69	I	2	2	2	2	2	5	2
69	D	5	5	5	5	10	20	5
69	insert	25	25	30	30	30	40	40
69	N	5	5	5	5	10	10	5
69	S	2	2	2	2	2	5	2
69	G	5	5	5	5	10	20	5
69	E	2	2	2	2	2	2	2
70	R	0	0	0	18	10	0	8
70	G	10	10	20	0	0	25	15
70	E	15	15	25	0	0	25	25
70	T	0	0	0	5	5	0	0
70	S	0	0	0	5	5	0	0
70	N	0	0	0	5	5	0	0
74	I	0	0	20	0	0	30	0
74	V	0	0	30	-5	0	60	0
75	A	0	0	5	5	15	10	5
75	I	5	5	5	5	10	10	5
75	M	0	0	5	5	30	20	5
75	T	0	0	5	5	50	20	5
75	S	0	0	5	5	20	10	0
75	L	0	0	2	2	2	2	2
77	L	5	5	10	10	10	10	5
100	I	0	0	0	-4	0	0	-4
115	F	0	0	25	0	0	0	10
116	Y	5	5	10	10	10	10	5
118	I	5	5	2	2	2	2	2
151	L	10	10	20	20	20	20	10
151	M	15	15	40	50	50	50	15
181	C	0	0	0	-4	0	0	-4
184	I	60	60	12	-8	-5	5	-8
184	V	60	60	12	-8	-5	5	-8
210	F	0	0	0	0	0	0	0
210	W	4	4	12	15	15	12	12
210	S	0	0	0	0	0	0	0
210	M	0	0	0	0	0	0	0
215	C	0	0	10	20	20	10	10
215	D	0	0	10	20	20	10	10
215	E	0	0	10	20	20	10	10
215	I	0	0	10	20	20	10	10
215	V	0	0	10	20	20	10	10
215	S	0	0	10	20	20	10	10
215	F	4	4	20	35	30	20	10
215	Y	4	4	20	35	30	20	20
215	Z	0	0	10	15	15	15	10
219	E	0	0	0	15	10	0	0
219	N	0	0	0	15	10	0	0
219	Q	0	0	0	15	10	0	0
219	R	0	0	0	10	5	0	0
219	W	0	0	5	10	10	5	5
219	T	0	0	5	10	5	0	0
333	D	0	0	0	5	0	0	0
333	E	0	0	0	5	0	0	0

NNRTI

Position	AA	DLV	EFV	NVP	ETR
98	G	5	5	10	5
98	S	0	0	0	0
100	I	40	40	40	20
100	V	10	10	10	10
101	E	30	15	30	15
101	P	30	30	30	15
101	Q	0	0	0	0
101	R	0	0	0	0
101	H	15	10	15	5
101	N	15	10	15	5
103	N	60	60	70	10
103	R	5	5	5	5
103	S	60	50	60	10
103	T	60	50	60	10
103	Q	10	10	10	5
103	E	15	10	15	5
106	A	50	25	60	10
106	M	60	60	60	10
106	I	0	0	0	0
106	L	10	5	10	0
108	I	10	10	10	5
138	K	20	10	20	20
179	D	10	10	10	10
179	E	10	10	10	10
179	I	0	0	0	0
179	T	0	0	0	0
179	G	0	0	0	0
179	A	0	0	0	0
179	F	30	15	30	40
179	M	10	10	10	10
181	C	60	20	60	30
181	I	60	20	60	30
181	V	60	20	60	30
181	S	30	10	30	10
188	C	25	25	60	10
188	H	25	25	25	15
188	L	30	60	60	20
190	A	0	40	60	15
190	C	0	60	60	20
190	E	15	60	60	30
190	Q	15	60	60	20
190	S	0	60	60	30
190	V	0	60	60	20
190	T	0	60	60	20
225	H	0	30	0	10
227	C	30	15	30	15
227	L	0	0	15	10
227	Y	0	0	10	0
227	S	0	0	0	0
230	L	60	40	60	20
234	I	10	10	10	10
236	L	60	0	0	0
236	S	25	0	0	0
238	T	30	15	30	0
238	N	30	12	30	0
238	R	0	0	0	0
318	F	50	12	30	0

PI

Position	AA	FPV	IDV	NFV	SQV	LPV	ATV	TPV	DRV
10	F	4	4	4	4	4	4	2	2
10	I	2	2	2	2	2	2	2	2
10	R	2	2	2	2	2	2	2	2
10	V	2	2	2	2	2	2	3	2
10	Y	2	2	2	2	2	2	2	2
11	I	4	2	2	2	2	2	2	4
11	F	0	0	0	0	0	0	0	0
11	T	0	0	0	0	0	0	0	0
11	C	0	0	0	0	0	0	0	0
16	A	0	0	0	0	0	0	0	0
16	E	0	0	0	0	0	0	0	0
20	I	0	0	0	0	0	0	0	0
20	M	0	0	0	0	0	0	0	0
20	R	0	0	0	0	0	0	0	0
20	T	0	0	0	0	0	0	0	0
20	V	0	0	0	0	0	0	0	0
20	L	0	0	0	0	0	0	0	0
23	I	0	0	15	0	0	0	0	0
24	I	2	5	2	2	2	2	0	2
24	F	1	1	1	1	1	1	1	1
30	N	0	0	50	0	0	0	0	0
32	I	20	10	5	5	10	10	8	10
32	A	5	5	5	5	5	5	5	5
33	F	5	0	0	0	5	5	8	5
33	V	0	0	0	0	0	0	0	0
33	I	0	0	0	0	0	0	0	0
35	G	0	0	0	0	0	0	2	0
36	I	0	0	0	0	0	0	0	0
36	L	0	0	0	0	0	0	0	0
36	V	0	0	0	0	0	0	0	0
36	T	0	0	0	0	0	0	0	0
36	A	0	0	0	0	0	0	0	0
43	T	0	0	0	0	0	0	2	0
46	I	12	12	25	5	12	15	8	4
46	L	12	12	25	5	12	15	8	4
46	V	10	10	20	5	10	10	8	4
47	V	20	5	5	5	10	5	10	12
47	A	20	5	5	5	40	5	5	10
48	V	5	10	25	50	10	30	0	0
48	M	5	10	25	50	10	30	0	0
48	A	0	5	15	30	5	5	0	0
48	S	0	5	15	30	5	5	0	0
48	T	0	5	15	30	5	5	0	0
50	V	50	0	5	0	20	0	-5	20
50	L	0	0	0	0	0	50	0	0
53	L	3	3	3	3	3	3	3	3
53	Y	2	2	2	2	2	2	2	2
54	L	15	10	15	10	12	10	0	10
54	M	20	10	15	10	12	10	5	12
54	S	10	10	15	10	10	10	5	4
54	T	10	10	15	10	10	10	5	4
54	V	10	10	15	15	12	10	10	4
54	A	10	10	10	10	10	10	15	4
58	E	0	0	5	0	0	0	5	0
63	P	0	0	0	0	0	0	0	0
71	T	1	1	1	1	1	1	1	1
71	V	3	3	3	3	3	3	3	2
71	I	2	2	2	2	2	2	2	2
73	C	2	5	5	10	2	5	2	2
73	S	2	5	5	10	2	5	2	2
73	T	2	5	5	10	2	5	2	2
73	A	2	5	5	5	2	5	2	2
74	P	0	0	10	2	0	0	10	5
74	S	0	0	10	0	0	0	0	0
76	V	12	12	5	-5	8	-5	-10	12
77	I	0	0	0	0	0	0	0	0
82	A	10	35	35	10	20	15	10	4
82	F	10	35	35	10	20	20	15	6
82	I	0	0	0	0	0	0	0	0
82	S	10	35	35	10	20	20	15	6
82	T	10	35	35	10	20	20	30	6
82	M	10	15	10	10	10	10	10	6
82	L	10	10	10	10	10	10	60	6
82	C	5	10	10	5	10	5	10	6
83	D	0	0	0	0	0	0	10	0
84	A	35	25	40	40	10	25	20	12
84	V	35	25	35	35	12	25	20	12
84	C	25	15	25	25	10	20	20	12
88	D	0	5	25	10	0	10	0	0
88	S	-10	10	40	5	0	30	0	0
88	T	0	5	25	5	0	15	0	0
88	G	0	5	25	5	0	15	0	0
89	V	4	2	4	1	1	1	1	4
89	I	0	0	0	0	0	0	0	0
89	T	0	0	0	0	0	0	0	0
89	M	0	0	0	0	0	0	0	0
90	M	15	20	50	35	10	20	6	6
93	L	0	0	0	0	0	0	0	0
93	M	0	0	0	0	0	0	0	0

Comments Section

Generic 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).
NRTI	$listHitsAt{74} partially reverses AZT and possibly d4T resistance caused by other mutations. AZT mutations in this isolate include: $listHitsAt{41,67,70,210,215,219}. $listHitsAt{184} partially reverses AZT, d4T, and TDF resistance caused by other AZT mutations (TAMs). AZT mutations in this isolate include: $listHitsAt{41,67,70,210,215,219}. $listHitsAt{100} partially reverses AZT and possibly d4T resistance caused by other mutations. AZT mutations in this isolate include: $listHitsAt{41,67,70,210,215,219}. $listHitsAt{181} partially reverses AZT and possibly d4T resistance caused by other mutations. AZT mutations in this isolate include: $listHitsAt{41,67,70,210,215,219}.
Generic DRV	The following $numberOfMutsIn{11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V} of the 11 darunavir POWER/DUET study mutations were present: $listMutsIn{11I,32I,33F,47V,50V,54LM,74P,76V,84V,89V} (DeMeyer S et al, EHDRW 2008).
PI	This sequence has $numberOfMutsIn{47V,54AMV,58E,74P,82LT,83D} major TPV-resistance mutations ($listMutsIn{47V,54AMV,58E,74P,82LT,83D}), $numberOfMutsIn{10V,36I,43T,46L,84V} minor TPV-resistance mutations ($listMutsIn{10V,36I,43T,46L,84V}), and $numberOfMutsIn{24I,50LV,54L,76V} mutations associated with increased TPV responsiveness ($listMutsIn{24I,50LV,54L,76V}). RESIST study (Baxter J et al J Virology 2006 and Scherer J et al EACS 2007).
Generic PR	L10I/V/F/R are associated with resistance to each of the PIs when present with other mutations. L10I/V occur commonly in 5-10% of untreated persons. L10FRY are nonpolymorphic. V11I is a nonpolymorphic accessory mutation weakly associated with PI therapy. It is one of the 11 mutations associated with decreased response to DRV in the POWER trials. I13V is a common polymorphism that is slightly more common in treated compared with untreated subtype B isolates. In subtypes A, AE, AG, and G it is the consensus residue. I13V was weakly associated with decreased virological response to TPV in the RESIST trials. G16E is a highly polymorphic mutation occurring in 2% to 20% of viruses depending on subtype. It may be weakly associated with ATV therapy and response. K20R/M/I/T are weakly associated with resistance to each of the PIs when present with other mutations. Many variants at this position occur commonly in non-subtype B viruses. L23I is a rare substrate cleft mutation that causes low-level resistance to NFV. L24F is a rare mutation at this position; its phenotypic effect is not known. L24I is associated with reduced susceptibility to IDV and possibly RTV, LPV, SQV, and ATV when present with other mutations. D30N causes intermediate resistance to NFV. V32I is a substrate cleft mutation that reduces susceptibility to IDV, RTV, FPV, LPV, TPV, and DRV. L33F are selected by FPV, DRV, LPV, ATV, and TPV, and slightly contribute resistance to these drugs. L33F are selected by FPV, DRV, LPV, ATV, and TPV, and slightly contribute resistance to these drugs. L33I is less common than L33F but may have a similar effect. L33V is a polymorphism that does not appear to be related to PI therapy or drug resistance. E35G is a nonpolymorphic mutation that is slightly more common in viruses from PI-treated (particularly NFV-treated) compared with untreated persons. It was weakly associated a decreased virological response to TPV in the RESIST trials. M36I/V are weakly associated with PI resistance when present with other mutations. M36I occurs commonly in certain non-subtype B viruses. M36L/T are rare variants of uncertain significance. K43T is a nonpolymorphic mutation that is significantly more common in viruses from PI-treated compared with untreated persons. It was weakly associated with a decreased virological response to TPV in the RESIST trials. M46I/L decreases susceptibility to IDV, NFV, FPV, LPV, ATV, TPV, and possibly SQV and DRV when present with other mutations. M46I/L decreases susceptibility to IDV, NFV, FPV, LPV, ATV, TPV, and possibly SQV and DRV when present with other mutations. M46V is a rare mutation at this position of uncertain significance. I47A usually occurs in combination with V32I and in this setting causes high-level LPV and FPV resistance and probably intermediate DRV resistance. I47V decrease susceptibility to FPV, ATV, IDV, LPV, TPV, and DRV. G48M causes high-level SQV resistance and intermediate resistance to NFV, ATV, IDV, and NFV. G48V causes high-level SQV resistance, intermediate ATV and NFV resistance, and low-level IDV and LPV resistance. I50L causes intermediate-to-high level resistance to ATV and hypersusceptibility to the remaining PIs. I50V causes intermediate-to-high-level resistance to FPV, intermediate resistance to LPV and DRV, and increased susceptibility to TPV. F53L occurs only in isolates from treated patients nearly always in combinations with other PI-resistance mutations. It is associated with decreased susceptibility to IDV, LPV, and SQV and possibly other PIs. F53Y is a rare treatment-associated variant. I54T/A/S are PI-related mutations typically observed in heavily treated persons and like I54V and I54M/L are likely to reduce susceptibility to most PIs. I54L occurs in patients receiving FPV, LPV, and DRV and reduces susceptibility to these drugs and to NFV and possibly ATV. It is associated with increased susceptibility to TPV. I54M occurs in patients receiving FPV, LPV, and DRV and reduces susceptibility to these drugs and to ATV and NFV. I54V contributes resistance to each of the PIs except possibly DRV when present with other mutations. Q58E is a nonpolymorphic mutation that occurs more commonly in treated patients. It has been associated with decreased virological response to TPV but probably is associated with resistance to multiple PIs. D60E is a polymorphic mutation that is slightly more common in viruses from PI-treated compared with untreated persons. It was weakly associated with a decreased virologic response to ATV in one of three retrospective analyses. I62V is a highly polymorphic mutation that is more common in PI-treated compared with untreated persons. It was weakly associated with a decreased virologic response to ATV in one of three retrospective analyses. L63P is a common polymorphism that becomes even more common in persons receiving PIs. H69K is a highly polymorphic residue that was weakly associated with a decreased virologic response to TPV in the RESIST trials. A71T/V are polymorphisms that occur in 1-2% of untreated persons but which become much more frequent in persons receiving PIs. A71I is an uncommon mutation that appears to occur only with PI therapy; its significance is not known. G73S/T/C/A are selected by and appear to be associated with decreased susceptibility to most, if not all, PIs. T74A is a polymorphic mutation more common in viruses from persons receiving PIs (particularly NFV and SQV) than in PI-naive persons. T74S is associated with reduced NFV susceptibility. It occasionally occurs in untreated persons. T74P is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It has been associated with decreased virological response to TPV but probably is associated with resistance to multiple PIs. L76V reduces susceptibility to FPV, IDV, LPV, and DRV and increases susceptibility to SQV and ATV. V77I is a common polymorphism that is associated with NFV therapy. V82A reduces susceptibility to IDV and LPV. With other mutations it is associated with reduced susceptibility to NFV, ATV, SQV, FPV, and TPV. V82C is a rare mutation that occurs primarily in protease genes containing multiple other PI-resistance mutations. V82F reduces susceptibility to IDV, LPV, FPV, and DRV. With other mutations it is associated with reduced susceptibility to NFV, ATV, SQV, and TPV. V82I is a polymorphism that is common in some non-B subtypes; it has little if any effect on PI susceptibility. V82L is a rare TPV-selected mutation. Its effect on other PIs has not been characterized. V82M has been shown to cause IDV resistance in subtype G viruses in which it is a common mutation. Its effect on other PIs has not been studied. V82S probably has a similar effect to V82T which reduces susceptibility to IDV, LPV, and TPV and with other mutations is associated with reduced susceptibility to NFV, ATV, FPV, and SQV. V82T reduces susceptibility to IDV, LPV, and TPV. With other mutations it is associated with reduced susceptibility to NFV, ATV, FPV, and SQV. N83D is a nonpolymorphic mutation that occurs more commonly in heavily treated patients. It has been associated with decreased virological response to TPV but probably is associated with resistance to multiple PIs. I84A/C are rare mutations that like I84V appear to reduce susceptibility to each of the PIs. I84V causes intermediate/high-level resistance to ATV, FPV, IDV, NFV, SQV, and TPV, and low-level intermediate resistance to LPV and DRV. I85V is a nonpolymorphic PI-selected mutation. It was weakly associated with a decreased virologic response to ATV in one of three retrospective analyses. N88G has not been studied but is likely to be similar to N88S which causes high-level resistance to NFV and ATV, low-level resistance to IDV, and increased susceptibility to FPV. N88S causes high-level resistance to NFV and ATV and low-level resistance to IDV; it increases susceptibility to FPV. N88T has not been studied but is likely to be similar to N88S which causes high-level resistance to NFV and ATV, low-level resistance to IDV, and increased susceptibility to FPV. L89V is an uncommon nonpolymorphic PI-selected accessory mutation. It is one of the 11 mutations associated with decreased response to DRV in the POWER trials. L90M causes resistance to NFV, SQV, ATV, and IDV. When present with other mutations it also compromises the activity of FPV, LPV, and TPV. Its effect on DRV is not known. I93L is a common polymorphism that becomes even more common in persons receiving PIs. I93M is a rare PI-associated mutation; its effect on PI susceptibility is not known.
Generic RT	M41L usually occurs with T215Y. Together these mutations confer intermediate-to-high level resistance to AZT and d4T and a lower level of resistance to ddI, ABC, and TDF. E44A/D occur in patients receiving multiple NRTIs. E44D causes low-level resistance to 3TC and probably to each of the other NRTIs when present with V118I or one or more TAMs. A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known. K65N is a rare mutation that is associated with reduced susceptibility to ddI, ABC, 3TC, FTC and TDF. K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF, and low-level resistance to d4T. K65R causes AZT hypersusceptibility. D67N contributes some degree of resistance to each of the NRTIs except 3TC and FTC. It usually occurs with mutations at positions 70 or 215. D67E/G occur in heavily treated patients but their precise effect on NRTI susceptibility is not known. D67N contributes some degree of resistance to each of the NRTIs except 3TC and FTC. It usually occurs with mutations at positions 70 or 215. Amino acid deletions (d) in this region occur uncommonly and are often assigned to position 67. They occur in combination with other NRTI mutations and contribute decreased susceptibility to each of the NRTIs. T69D contributes resistance to ddI and d4T. T69G occurs in isolates with a deletion at position 67 but its effect on NRTI susceptibility is not known. T69N/S/A/I are NRTI-selected mutations but their effect on NRTI susceptibility is not known. Amino acid insertions (i) at this position occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to each of the NRTIs. Most susceptibility data are available for double amino acid insertions. However, insertions of 1 or >2 amino acids also occur. K70E reduces TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility. K70E does not reduce AZT or d4T susceptibility. K70G appears to reduce TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility. K70G does not reduce AZT susceptibility. Its effect on d4T susceptibility is not known. K70N is a rare NRTI-selected variant. Its effect on drug susceptibility is not known. K70R causes low-level AZT, d4T, and possibly TDF resistance and appears to have little if any effect on the other NRTIs. L74I, like L74V, reduces ddI and ABC susceptibility. L74V reduces ddI and ABC susceptibility. L74V increases AZT and TDF susceptibility. V75I increases multinucleoside resistance caused by Q151M when present with F77L and F116Y; its effect in the absence of Q151M is not known. V75TM/A reduce d4T and possibly ddI susceptibility. Like V75T, V75S may also reduce d4T and ddI susceptibility. V75T reduces d4T and ddI susceptibility. F77L increases multinucleoside resistance caused by Q151M when present with V75I or F116Y; its effect in the absence of Q151M is not known. A98G occurs in about 1% of NNRTI-naive persons and causes low-level NVP resistance. A98G occurs in about 1% of NNRTI-naive persons and causes low-level NVP resistance. A98S is a common polymorphism that does not reduce NNRTI susceptibility. L100I causes intermediate resistance to NVP, DLV, and EFV, and low-resistance to ETR. It nearly always in combination with K103N. L100I increases susceptibility to AZT and TDF. K101E is associated with intermediate resistance to NVP and DLV and low-level resistance to EFV and ETR. K101H/N are NNRTI-associated mutations with uncertain phenotypic and clinical effects. K101P usually occurs with K103N and in this setting causes high-level resistance to NVP, DLV, and EFV and low-intermediate resistance to ETR. K101Q/R occasionally occur in untreated persons and do not decrease NNRTI susceptibility. K103N causes high-level resistance to NVP, DLV, and EFV. By itself it has no effect on ETR susceptibility. K103Q is a rare mutation. It has not been associated with NNRTI resistance. K103R occurs in about 1%-2% of untreated persons and by itself has no effect on NNRTI susceptibility. However, the combination of K103R + V179D, reduces intermediate resistance to NVP, DLV, and EFV. K103S causes high-level resistance to NVP and intermediate resistance to DLV and EFV. K103T/H are rare mutations that appear to be associated with high-level resistance to NVP, DLV, and EFV. V106A causes high-level NVP resistance, intermediate DLV resistance, and low-level EFV and ETR resistance. V106I is a common polymorphism that does not decrease NNRTI susceptibility. However, in a multivariate analysis it was associated with decreased ETR response in the DUET study. V106L is a rare mutation of uncertain significance. V106M causes high-level resistance to NVP, EFV, and DLV but does not appear to decrease ETR susceptibility. V108I causes low-level reductions in susceptibility to each of the NNRTIs except possibly ETR. Y115F causes intermediate resistance to ABC and low-level resistance to TDF. F116Y increases multinucleoside resistance caused by Q151M when present with F77L or V75I; its effect in the absence of Q151M is not known. V118I occurs in ~2% of untreated persons and with increased frequency in persons receiving multiple NRTIs. It causes low-level resistance to 3TC and possibly to other NRTIs when present with E44A/D and/or one or more TAMs. E138K is selected in vitro by ETR and reduces its susceptibility by about 5-fold. E138K reduces susceptibility other NNRTIs by about 2-5 fold. By itself, Q151M causes intermediate resistance to AZT, ddI, d4T, and ABC; and low-level resistance to TDF. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC; intermediate resistance to TDF, and low-level resistance to 3TC and FTC. Q151L is a rarely observed transitional mutation that appears to precede the emergence of the Q151M. By itself, Q151M causes intermediate resistance to AZT, ddI, d4T, and ABC; and low-level resistance to TDF. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC; intermediate resistance to TDF, and low-level resistance to 3TC and FTC. V179D/E cause low-level reductions in susceptibility to each of the NNRTIs. V179D occurs in about 1% of untreated persons. The combination of K103R + V179D reduces the susceptibility of NVP, DLV, and EFV by about 15-fold; the combination's effect on ETR is not known. V179F nearly always occurs in combination with Y181C. The combination of V179F + Y181C reduces ETR susceptibility >100-fold and causes low-level EFV resistance. V179I is a common polymorphism that does not decrease NNRTI susceptibility. Y181C/I/V cause high-level resistance to NVP and DLV and low-level resistance to EFV. Y181C/I/V reduces ETR susceptibility by 5-10 fold and lays the mutational foundation for the development of higher levels of ETR resistance. Y181C increases susceptibility to AZT and TDF. M184V/I cause high-level in vitro resistance to 3TC and FTC and low-level in vitro resistance to ddI and ABC. M184V/I increase susceptibility to AZT, TDF, and d4T. Y188C causes high-level resistance to NVP and low-level resistance to EFV and DLV; its effect on ETR is not known. Y188H causes low-level resistance to NVP, EFV, and DLV and has been selected in vitro by ETR. Y188L causes high-level resistance to NVP and EFV and low-level resistance to ETR and DLV. G190A causes high level resistance to NVP, intermediate resistance to EFV, and low-level ETR resistance. G190A increases DLV susceptibility. G190C/T/V are rare mutations that cause high-level resistance to NVP and EFV and variable resistance to DLV. Their effect on ETR is not known. G190E/Q cause high-level resistance to NVP and EFV and intermediate resistance to DLV. G190E + Y181C is associated with >100-fold decreased ETR susceptibility. G190S causes high-level resistance to NVP and EFV and low-level / intermediate resistance to ETR. G190S increases DLV susceptibility. L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. L210F/S occur rarely and are of unknown significance. L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and to a lesser extent TDF. T215S/C/D/E/I/V/A/N represent transitions between wild type and the mutations Y and F. Most of these mutations do not reduce NRTI susceptibility but their presence suggests that a resistant virus may have been transmitted. T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W. K219N/R occur commonly in heavily NRTI-treated patients. Their effect on NRTI susceptibility is uncertain. K219Q/E decrease AZT and probably d4T susceptibility when present with K70R or T215Y/F but have little if any effect on the remaining NRTIs. P225H increases EFV resistance when present in combination with K103N. F227C is a rare mutation which has been associated with inconsistently reported levels of resistance to each of the NNRTIs particularly ETR. F227L usually occurs in combination with V106A and in this setting is associated with high level resistance to NVP and intermediate resistance to DLV and EFV. Its effect on ETR is not known. M230L causes intermediate-to-high-level resistance to each of the NNRTIs. It has been selected in vitro by ETR and reduces ETR susceptibility by about 10-fold. 234I has been selected in vitro by etravirine and it acts synergistically with Y181C to reduce etravirine susceptibility. Its clinical significance and effect on other NNRTIs is not known. P236L causes high-level DLV resistance. K238N/T are NNRTI-selected mutations that usually occur in combination with other NNRTI-resistance mutations and which appear to confer intermediate levels of resistance to NVP and possibly DLV and EFV. K238R is a naturally occurring variant that is common in some non-B subtypes and does not reduce NNRTI susceptibility. Y318F is a rare mutation that causes high-level DLV resistance and low/intermediate NVP resistance. It usually occurs with other NNRTI-associated mutations. G333D/E are polymorphisms that occur more frequently in persons receiving NRTIs than in untreated persons. They may facilitate AZT resistance in isolates that contain M184V and multiple TAMs.