Antiretroviral resistance in HIV

• Genotyping sequences reverse transcriptase, integrase, and protease
• Resistance point mutations names as wild-type amino acid, position, and mutant amino acid (e.g. K 103 N)
• Bulk sequencing can only detect mutations that represent >20% of HIV

Common Mutations

• NRTIs
  • M184V/I confers resistance to lamivudine, emtricitabine, and abacavir, but increases susceptibility to tenofovir, so combinations that include tenofovir are still safe to use
  • K65R confers resistance to lamivudine, emtricitabine, and abacavir
  • TAMS (M41L, D76N, K70R, L210W, T215Y, K219Q) confer resistance to basically all NRTIs as they increase in number
  • Q151M, 69SSS confers resistance to NRTIs
• NNRTIs
  • K103N confers resistance to efavirenz and nevirapine
  • Y181C confers resistance to nevirapine and other NNRTIs
  • E138K and K101E confer resistance to rilpivirine and other NNRTIs
  • I50L confers resistance to atazanavir
• INSTIs
  • N155H and Q148H/R?K confer resistance to raltegravir and elvitegravir
  • Y143C confers resistance to raltegravir
  • R263K confers resistance to dolutegravir

All Mutations

Drug	Mutation	Notes
NRTIs
69 insertion complex	M 41 L	multi-NRTI resistance
	A 62 V
	* 69 insert
	K 70 R
	L 210 W
	T 215 Y F
	K 219 Q E
151 complex	A 62 V	multi-NRTI resistance
	V 75 I
	F 77 L
	F 116 Y
	Q 151 M
Thymidine analogue-associated mutations (TAMs)	M 41 L	resistance to AZT and d4T; resistance to others is proportional to the number of TAMs, and with 4 or more mutations there is resistance to essentially all NRTIs
	D 67 N
	K 70 R
	L 210 W
	T 215 Y F
	K 219 Q W
Abacavir	K 65 R E N	common
	L 74 V
	Y 115 F
	M 184 V	common; can still use TDF, AZT
Emtricitabine	K 65 R E N	common
	M 184 V I	common; can use ABC (if M184I), TDF, AZT; can still use FTC in combination with TDF or TAF
Lamivudine	K 65 R E N	common
	M 184 V I	common; can use ABC (if M184I), TDF, AZT; can still use 3TC in combination with TDF or TAF
Tenofovir	K 65 R E N	common
	K 70 E
Zidovudine	M 41 L
	D 67 N
	K 70 R
	L 210 W
	T 215 Y F
	K 219 Q E
NNRTIs
Doravirine	V 106 A I M T
	Y 188 C L H
	G 190 E
	P 225 H
	F 227 C L R
	M 230 L
	L 234 I
Efavirenz	L 100 I
	K 101 P
	K 103 N S
	V 106 M
	V 108 I
	Y 181 C I
	Y 188 L
	G 190 S A
	P 225 H
	M 230 L
Nevirapine	L 100 I
	K 101 P
	K 103 N S
	V 106 A M
	V 108 I
	Y 181 C I	common
	Y 188 C L H
	G 190 A
	M 230 L
Rilpivirine	L 100 I
	K 101 E P	common
	E 138 A G K Q R	common
	V 179 L
	Y 181 C I V	common
	Y 188 L
	H 221 Y
	F 227 C
	M 230 I L
Protease inhibitors
Atazanavir	L 10 I F V C
	G 16 E
	K 20 R M I T V
	L 24 I
	V 32 I
	L 33 I F V
	E 34 Q
	M 36 I L V
	M 46 I L
	G 48 V
	I 50 L	common
	F 53 L Y
	I 54 L V M T A
	D 60 E
	I 62 V
	I 64 L M V
	A 71 V I T L
	G 73 C S T A
	V 82 A T F I
	I 84 V
	I 85 V
	N 88 S
	L 90 M
	I 93 L M
Darunavir	V 11 I
	V 32 I
	L 33 F
	I 47 V
	I 50 V
	I 54 M L
	T 74 P
	L 76 V
	I 84 V
	L 89 V
INSTIs
Bictegravir	G 118 R
	E 138 K
	G 140 S
	Q 148 H
	R 263 K
Cabotegravir	T 66 K
	G 118 R
	E 138 A K T
	G 140 A C R S
	Q 148 H K R
	S 153 F Y
	N 155 H
	R 263 K
Dolutegravir	G 118 R
	F 121 Y
	E 138 A K T
	G 140 A S
	Q 148 H K R
	N 155 H
	R 263 K	common
Elvitegravir	T 66 I A K
	E 92 Q G
	T 97 A
	F 121 Y
	S 147 G
	Q 148 H K R	common
	N 155 H	common
	R 263 K
Raltegravir	L 74 M
	E 92 Q
	T 97 A
	F 121 Y
	E 138 A K
	G 140 A S
	Y 143 R H C	common
	Q 148 H K R	common
	N 155 H	common
	R 263 K