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	M41L	multi-NRTI resistance
	A62V
	* 69 insert
	K70R
	L210W
	T215YF
	K219QE
151 complex	A62V	multi-NRTI resistance
	V75I
	F77L
	F116Y
	Q151M
Thymidine analogue-associated mutations (TAMs)	M41L	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
	D67N
	K70R
	L210W
	T215Y/F
	K219Q/W
Abacavir	K65R/E/N	common
	L74V
	Y115F
	M184V	common; can still use TDF, AZT
Emtricitabine	K65R/E/N	common
	M184V/I	common; can use ABC (if M184I), TDF, AZT; can still use FTC in combination with TDF or TAF
Lamivudine	K65R/E/N	common
	M184V/I	common; can use ABC (if M184I), TDF, AZT; can still use 3TC in combination with TDF or TAF
Tenofovir	K65R/E/N	common
	K70E
Zidovudine	M41L
	D67N
	K70R
	L210W
	T215Y/F
	K219Q/E
NNRTIs
Doravirine	V106A/I/M/T
	Y188C/L/H
	G190E
	P225H
	F227C/L/R
	M230L
	L234I
Efavirenz	L100I
	K101P
	K103N/S
	V106M
	V108I
	Y181C/I
	Y188L
	G190S/A
	P225H
	M230L
Nevirapine	L100I
	K101P
	K103N/S
	V106A/M
	V108I
	Y181C/I	common
	Y188C/L/H
	G190A
	M230L
Rilpivirine	L100I
	K101E/P	common
	E138A/G/K/Q/R	common
	V179L
	Y181C/I/V	common
	Y188L
	H221Y
	F227C
	M230I/L
Protease inhibitors
Atazanavir	L10I/F/V/C
	G16E
	K20R/M/I/T/V
	L24I
	V32I
	L33I/F/V
	E34Q
	M36I/L/V
	M46I/L
	G48V
	I50L	common
	F53L/Y
	I54L/V/M/T/A
	D60E
	I62V
	I64L/M/V
	A71V/I/T/L
	G73C/S/T/A
	V82A/T/F/I
	I84V
	I85V
	N88S
	L90M
	I93L/M
Darunavir	V11I
	V32I
	L33F
	I47V
	I50V
	I54M/L
	T74P
	L76V
	I84V
	L89V
INSTIs
Bictegravir	G118R
	E138K
	G140S
	Q148H
	R263K
Cabotegravir	T66K
	G118R
	E138A/K/T
	G140A/C/R/S
	Q148H/K/R
	S153F/Y
	N155H
	R263K
Dolutegravir	G118R
	F121Y
	E138A/K/T
	G140A/S
	Q148H/K/R
	N155H
	R263K	common
Elvitegravir	T66I/A/K
	E92Q/G
	T97A
	F121Y
	S147G
	Q148H/K/R	common
	N155H	common
	R263K
Raltegravir	L74M
	E92Q
	T97A
	F121Y
	E138A/K
	G140A/S
	Y143R/H/C	common
	Q148H/K/R	common
	N155H	common
	R263K