Antiretroviral resistance in HIV: Difference between revisions

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*Bulk sequencing can only detect mutations that represent >20% of HIV
*Bulk sequencing can only detect mutations that represent >20% of HIV


== Common Mutations ==
==Common Mutations==


* NRTIs
*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
**'''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]]
**'''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
**'''TAMS (M41L, D76N, K70R, L210W, T215Y, K219Q)''' confer resistance to basically all NRTIs as they increase in number
** '''Q151M, 69SSS''' confers resistance to NRTIs
**'''Q151M, 69SSS''' confers resistance to NRTIs
* NNRTIs
*NNRTIs
** '''K103N''' confers resistance to [[efavirenz]] and [[nevirapine]]
**'''K103N''' confers resistance to [[efavirenz]] and [[nevirapine]]
** '''Y181C''' confers resistance to [[nevirapine]] and other NNRTIs
**'''Y181C''' confers resistance to [[nevirapine]] and other NNRTIs
** '''E138K and K101E''' confer resistance to [[rilpivirine]] and other NNRTIs
**'''E138K and K101E''' confer resistance to [[rilpivirine]] and other NNRTIs
** '''I50L''' confers resistance to [[atazanavir]]
**'''I50L''' confers resistance to [[atazanavir]]
* INSTIs
*INSTIs
** '''N155H and Q148H/R?K''' confer resistance to [[raltegravir]] and [[elvitegravir]]
**'''N155H and Q148H/R?K''' confer resistance to [[raltegravir]] and [[elvitegravir]]
** '''Y143C''' confers resistance to [[raltegravir]]
**'''Y143C''' confers resistance to [[raltegravir]]
** '''R263K''' confers resistance to [[dolutegravir]]
**'''R263K''' confers resistance to [[dolutegravir]]


== All Mutations ==
==All Mutations==
{| class="wikitable"
{| class="wikitable"
!Drug
!Drug
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! colspan="3" |NRTIs
! colspan="3" |NRTIs
|-
|-
| rowspan="7" |69 insertion complex multi-NRTI resistance
| rowspan="7" |69 insertion complex
|M '''41''' '''L'''
|M'''41L'''
| rowspan="7" |multi-NRTI resistance
|
|-
|-
|A '''62''' '''V'''
|A'''62V'''
|
|-
|-
|* '''69''' '''insert'''
|* '''69''' '''insert'''
|
|-
|-
|K '''70''' '''R'''
|K'''70R'''
|
|-
|-
|L '''210''' '''W'''
|L'''210W'''
|
|-
|-
|T '''215''' '''Y F'''
|T'''215YF'''
|
|-
|-
|K '''219''' '''Q E'''
|K'''219QE'''
|
|-
|-
| rowspan="5" |151 complex multi-NRTI resistance
| rowspan="5" |151 complex
|A '''62''' '''V'''
|A'''62V'''
| rowspan="5" |multi-NRTI resistance
|
|-
|-
|V '''75''' '''I'''
|V'''75I'''
|
|-
|-
|F '''77''' '''L'''
|F'''77L'''
|
|-
|-
|F '''116''' '''Y'''
|F'''116Y'''
|
|-
|-
|Q '''151''' '''M'''
|Q'''151M'''
|
|-
|-
| rowspan="6" |Thymidine analogue-associated mutations (TAMs) multi-NRTI resistance
| rowspan="6" |Thymidine analogue-associated mutations (TAMs)
|M '''41''' '''L'''
|M'''41L'''
| rowspan="6" |resistance to AZT and d4T; resistance to others is proportional to the number of TAMs
| rowspan="6" |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'''
|D'''67N'''
|-
|-
|K '''70''' '''R'''
|K'''70R'''
|-
|-
|L '''210''' '''W'''
|L'''210W'''
|-
|-
|T '''215''' '''Y F'''
|T'''215Y/F'''
|-
|-
|K '''219''' '''Q W'''
|K'''219Q/W'''
|-
|-
| rowspan="4" |[[Abacavir]]
| rowspan="4" |[[Abacavir]]
|K '''65''' '''R E N'''
|K'''65R/E/N'''
|common
|
|-
|-
|L '''74''' '''V'''
|L'''74V'''
|
|
|-
|-
|Y '''115''' '''F'''
|Y'''115F'''
|
|
|-
|-
|M '''184''' '''V'''
|M'''184V'''
|common; can still use TDF, AZT
|common; can still use TDF, AZT
|-
|-
| rowspan="2" |[[Emtricitabine]]
| rowspan="2" |[[Emtricitabine]]
|K '''65''' '''R E N'''
|K'''65R/E/N'''
|common
|
|-
|-
|M '''184''' '''V I'''
|M'''184V/I'''
|common; can use ABC (if M184I), TDF, AZT; can still use FTC in combination with TDF or TAF
|common; can use ABC (if M184I), TDF, AZT; can still use FTC in combination with TDF or TAF
|-
|-
| rowspan="2" |[[Lamivudine]]
| rowspan="2" |[[Lamivudine]]
|K '''65 '''R E N
|K'''65'''R/E/N
|common
|
|-
|-
|M '''184''' '''V I'''
|M'''184V/I'''
|common; can use ABC (if M184I), TDF, AZT; can still use 3TC in combination with TDF or TAF
|common; can use ABC (if M184I), TDF, AZT; can still use 3TC in combination with TDF or TAF
|-
|-
| rowspan="2" |[[Tenofovir]]
| rowspan="2" |[[Tenofovir]]
|K '''65''' '''R E N'''
|K'''65R/E/N'''
|common
|
|-
|-
|K '''70''' '''E'''
|K'''70E'''
|
|
|-
|-
| rowspan="6" |[[Zidovudine]]
| rowspan="6" |[[Zidovudine]]
|M '''41''' '''L'''
|M'''41L'''
|
|
|-
|-
|D '''67''' '''N'''
|D'''67N'''
|
|
|-
|-
|K '''70''' '''R'''
|K'''70R'''
|
|
|-
|-
|L '''210''' '''W'''
|L'''210W'''
|
|
|-
|-
|T '''215''' '''Y F'''
|T'''215Y/F'''
|
|
|-
|-
|K '''219''' '''Q E'''
|K'''219Q/E'''
|
|
|-
|-
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|-
|-
| rowspan="7" |[[Doravirine]]
| rowspan="7" |[[Doravirine]]
|V '''106''' '''A''' I '''M''' T
|V'''106A'''/I/'''M'''/T
|
|
|-
|-
|Y '''188''' C '''L''' H
|Y'''188'''C/'''L'''/H
|
|
|-
|-
|G '''190''' E
|G'''190'''E
|
|
|-
|-
|P '''225''' H
|P'''225'''H
|
|
|-
|-
|F '''227''' C L R
|F'''227'''C/L/R
|
|
|-
|-
|M '''230''' L
|M'''230'''L
|
|
|-
|-
|L '''234''' I
|L'''234'''I
|
|
|-
|-
| rowspan="10" |[[Efavirenz]]
| rowspan="10" |[[Efavirenz]]
|L '''100''' '''I'''
|L'''100I'''
|
|
|-
|-
|K '''101''' '''P'''
|K'''101P'''
|
|
|-
|-
|K '''103''' '''N S'''
|K'''103N'''/'''S'''
|
|
|-
|-
|V '''106''' '''M'''
|V'''106M'''
|
|
|-
|-
|V '''108''' '''I'''
|V'''108I'''
|
|
|-
|-
|Y '''181''' '''C I'''
|Y'''181C'''/'''I'''
|
|
|-
|-
|Y '''188''' '''L'''
|Y'''188L'''
|
|
|-
|-
|G '''190''' '''S A'''
|G'''190S'''/'''A'''
|
|
|-
|-
|P '''225''' '''H'''
|P'''225H'''
|
|
|-
|-
|M '''230''' '''L'''
|M'''230L'''
|
|
|-
|-
| rowspan="9" |[[Nevirapine]]
| rowspan="9" |[[Nevirapine]]
|L '''100''' '''I'''
|L'''100I'''
|
|
|-
|-
|K '''101''' '''P'''
|K'''101P'''
|
|
|-
|-
|K '''103''' '''N S'''
|K'''103N'''/'''S'''
|
|
|-
|-
|V '''106''' '''A M'''
|V'''106A'''/'''M'''
|
|
|-
|-
|V '''108''' '''I'''
|V'''108I'''
|
|
|-
|-
|Y '''181''' '''C I'''
|Y'''181C'''/'''I'''
|common
|
|-
|-
|Y '''188''' '''C L H'''
|Y'''188C'''/'''L'''/'''H'''
|
|
|-
|-
|G '''190''' '''A'''
|G'''190A'''
|
|
|-
|-
|M '''230''' '''L'''
|M'''230L'''
|
|
|-
|-
| rowspan="9" |[[Rilpivirine]]
| rowspan="9" |[[Rilpivirine]]
|L '''100''' '''I'''
|L'''100I'''
|
|
|-
|-
|K '''101''' '''E P'''
|K'''101E'''/'''P'''
|common
|
|-
|-
|E '''138''' '''A G K Q R'''
|E'''138A'''/'''G'''/'''K'''/'''Q'''/'''R'''
|common
|
|-
|-
|V '''179''' '''L'''
|V'''179L'''
|
|
|-
|-
|Y '''181''' '''C I V'''
|Y'''181C'''/'''I'''/'''V'''
|common
|
|-
|-
|Y '''188''' '''L'''
|Y'''188L'''
|
|
|-
|-
|H '''221''' '''Y'''
|H'''221Y'''
|
|
|-
|-
|F '''227''' '''C'''
|F'''227C'''
|
|
|-
|-
|M '''230''' '''I L'''
|M'''230I'''/'''L'''
|
|
|-
|-
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|-
|-
| rowspan="24" |[[Atazanavir]]
| rowspan="24" |[[Atazanavir]]
|L '''10''' I F V C
|L'''10'''I/F/V/C
|
|
|-
|-
|G '''16''' E
|G'''16'''E
|
|
|-
|-
|K '''20''' R M I T V
|K'''20'''R/M/I/T/V
|
|
|-
|-
|L '''24''' I
|L'''24'''I
|
|
|-
|-
|V '''32''' I
|V'''32'''I
|
|
|-
|-
|L '''33''' I F V
|L'''33'''I/F/V
|
|
|-
|-
|E '''34''' Q
|E'''34'''Q
|
|
|-
|-
|M '''36''' I L V
|M'''36'''I/L/V
|
|
|-
|-
|M '''46''' I L
|M'''46'''I/L
|
|
|-
|-
|G '''48''' V
|G'''48'''V
|
|
|-
|-
|I '''50''' '''L'''
|I'''50L'''
|common
|
|-
|-
|F '''53''' L Y
|F'''53'''L/Y
|
|
|-
|-
|I '''54''' L V M T A
|I'''54'''L/V/M/T/A
|
|
|-
|-
|D '''60''' E
|D'''60'''E
|
|
|-
|-
|I '''62''' V
|I'''62'''V
|
|
|-
|-
|I '''64''' L M V
|I'''64'''L/M/V
|
|
|-
|-
|A '''71''' V I T L
|A'''71'''V/I/T/L
|
|
|-
|-
|G '''73''' C S T A
|G'''73'''C/S/T/A
|
|
|-
|-
|V 82 A T F I
|V82A/T/F/I
|
|
|-
|-
|I '''84''' '''V'''
|I'''84V'''
|
|
|-
|-
|I85V
|I 85 V
|
|
|-
|-
|N '''88''' '''S'''
|N'''88S'''
|
|
|-
|-
|L90M
|L 90 M
|
|
|-
|-
|I 93 L M
|I93L/M
|
|
|-
|-
| rowspan="10" |[[Darunavir]]
| rowspan="10" |[[Darunavir]]
|V11I
|V 11 I
|
|
|-
|-
|V32I
|V 32 I
|
|
|-
|-
|L33F
|L 33 F
|
|
|-
|-
|I '''47''' '''V'''
|I'''47V'''
|
|
|-
|-
|I '''50''' '''V'''
|I'''50V'''
|
|
|-
|-
|I '''54''' '''M L'''
|I'''54M'''/'''L'''
|
|
|-
|-
|T74P
|T 74 P
|
|
|-
|-
|L '''76''' '''V'''
|L'''76V'''
|
|
|-
|-
|I '''84''' '''V'''
|I'''84V'''
|
|
|-
|-
|L89V
|L 89 V
|
|
|-
|-
Line 353: Line 343:
|-
|-
| rowspan="5" |[[Bictegravir]]
| rowspan="5" |[[Bictegravir]]
|G118R
|G 118 R
|
|
|-
|-
|E138K
|E 138 K
|
|
|-
|-
|G140S
|G 140 S
|
|
|-
|-
|Q '''148''' '''H'''
|Q'''148H'''
|
|
|-
|-
|R '''263''' '''K'''
|R'''263K'''
|
|
|-
|-
| rowspan="8" |[[Cabotegravir]]
| rowspan="8" |[[Cabotegravir]]
|T66K
|T 66 K
|
|
|-
|-
|G '''118''' '''R'''
|G'''118R'''
|
|
|-
|-
|E 138 A K T
|E138A/K/T
|
|
|-
|-
|G '''140''' A C '''R''' S
|G'''140'''A/C/'''R'''/S
|
|
|-
|-
|Q '''148''' '''H K R'''
|Q'''148H'''/'''K/R'''
|
|
|-
|-
|S153F/Y
|S 153 F Y
|
|
|-
|-
|N155H
|N 155 H
|
|
|-
|-
|R '''263''' '''K'''
|R'''263K'''
|
|
|-
|-
| rowspan="7" |[[Dolutegravir]]
| rowspan="7" |[[Dolutegravir]]
|G '''118''' '''R'''
|G'''118R'''
|
|
|-
|-
|F121Y
|F 121 Y
|
|
|-
|-
|E 138 A K T
|E138A/K/T
|
|
|-
|-
|G140A/S
|G 140 A S
|
|
|-
|-
|Q '''148''' '''H K R'''
|Q'''148H'''/'''K'''/'''R'''
|
|
|-
|-
|N155H
|N 155 H
|
|
|-
|-
|R '''263''' '''K'''
|R'''263K'''
|common
|
|-
|-
| rowspan="8" |[[Elvitegravir]]
| rowspan="8" |[[Elvitegravir]]
|T '''66''' '''I''' A K
|T'''66I'''/A/K
|
|
|-
|-
|E '''92''' '''Q''' G
|E'''92Q'''/G
|
|
|-
|-
|T97A
|T 97 A
|
|
|-
|-
|F '''121''' '''Y'''
|F'''121Y'''
|
|
|-
|-
|S '''147''' '''G'''
|S'''147G'''
|
|
|-
|-
|Q '''148''' '''H K R'''
|Q'''148H'''/'''K'''/'''R'''
|common
|
|-
|-
|N '''155''' '''H'''
|N'''155H'''
|common
|
|-
|-
|R '''263''' '''K'''
|R'''263K'''
|
|
|-
|-
| rowspan="10" |[[Raltegravir]]
| rowspan="10" |[[Raltegravir]]
|L74M
|L 74 M
|
|
|-
|-
|E92Q
|E 92 Q
|
|
|-
|-
|T97A
|T 97 A
|
|
|-
|-
|F '''121''' '''Y'''
|F'''121Y'''
|
|
|-
|-
|E138A/K
|E 138 A K
|
|
|-
|-
|G140A/S
|G 140 A S
|
|
|-
|-
|Y '''143''' '''R H C'''
|Y'''143R'''/'''H'''/'''C'''
|common
|
|-
|-
|Q '''148''' '''H K R'''
|Q'''148H'''/'''K'''/'''R'''
|common
|
|-
|-
|N '''155''' '''H'''
|N'''155H'''
|common
|
|-
|-
|R '''263''' '''K'''
|R'''263K'''
|
|
|}
|}

Latest revision as of 12:59, 22 October 2020

  • 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

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
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