HIV Resistance mutations

Question 1

M184V - Affected class

Answer 1

NRTI

Question 2

M184V - high level resistance (2)

Answer 2

3TC (lamivudine)

FTC (emtricitabine)

Question 3

M184V - low level resistance (2)

Answer 3

ddI (didanosine)

ABC (abacavir)

Question 4

M184V - Increased susceptibility (3)

Answer 4

ZDV (zidovudine)
d4T (stavudine)
TDF (tenofovir)

Question 5

M184V - mechanism

Answer 5

Decreases NRTI incorporation

Question 6

Thymidine analog mutations (TAMs) - Resistance (2)

Answer 6

ZDV (zidovudine)

d4T (stavudine)

Question 7

TAMs mildly resistance (3)

Answer 7

ABC (abacavir)
ddI (didanosine)
TDF (tenofovir)

Question 8

TAM mechanism

Answer 8

Enhanced removal of incorporated NRTI by promoting phosphorolytic reaction that leads to primer unblocking

Question 9

Needed for high-level ABC and ddI resistance

Answer 9

M184V and 3+ TAMs

Question 10

M41L
L210W
T215Y

Answer 10

Type I TAMs

Question 11

D67N
K70R
T215F
K219Q/E

Answer 11

Type II TAMs

Question 12

4+ Of 41, 67, 70, 210, 215, 219

Answer 12

Resistance to all NRTIS

Question 13

What drugs to Type I TAMs cause cross-resistance to? (3)

Answer 13

ABC
ddI
TDF

Question 14

K65R Resistance

Answer 14

All NRTI except ZDV

Question 15

K65R - Increased susceptibility (1)

Answer 15

ZDV

Question 16

L74V - Intermediate resistance (2)

Answer 16

ddI

ABC

Question 17

L74V - Slight increase susceptibility (2)

Answer 17

ZDV

TDF

Question 18

NNRTI Resistance mechanisms

Answer 18

NNRTIs inhibit reverse transcriptase by binding hydrophobic pocket close but not contiguous with RT active site, mutations are within pockets or adjacent residues

Question 19

Primary NNRTI resistance mutations

Answer 19

K103N/S
V106A/M
Y181C/I/V
Y188L/C/H
G190A/S/E
E138K

Question 20

K103N resistance

Answer 20

EFV (efavirenz)

NVP (Nevirapine)

Question 21

V106

Answer 21

Resistance to DRV

Question 22

T69 insertion selected by

Answer 22

DDI

D4t

Question 23

T69 insertion high level resistance

Answer 23

Tenofovir
ABC
DDI

Question 24

T69 insertion decreased susceptibility (2)

Answer 24

3tc

FTC

Question 25

Q151m selected by

Answer 25

DDI

ZDV

Question 26

Q151M High level resistance

Answer 26

ABC
DDI
Thymidine analogs

Question 27

Q151 low level resistance

Answer 27

3tc
FTC
Tenofovir

Question 28

K103N high level resistance

Answer 28

EFV
NVP
(Rilpivirine and etravirine susceptible)

Question 29

Y181C selected by

Answer 29

Nevirapine

Question 30

Y181C resistance (one high level, 3 low)

What NNRTI still works?

Answer 30

High level R nevirapine
Decreased susceptibility to EFV, RPV, ETV)

Doravirine still works (only)!

Question 31

E138K selected by

Answer 31

RPV

Question 32

E138K resistance

Answer 32

Decreased susceptibility to RPV, ETR, causes failure with K101E

Question 33

Q148R selected by

Answer 33

RAL

EVG

Question 34

Q148R resistance

Answer 34

High level to Raltegravir, elvitegravir
Also R to bic and dtg
Increase dolutegravir to bid if present

Question 35

N155H resistance

Answer 35

High level resistance to RAL, EVG

Decreased DTG and BIC if Q148R also present

Question 36

I50L selected by

Answer 36

Atazanavir

Question 37

I50L resistance

Answer 37

High level Atazanavir

Increase suspect. Other PIs

Question 38

Y188L selected by

Answer 38

NVP, EFV

+/- DOR

Question 39

Y188L Resistance

Answer 39

NVP, EFV

+/- DOR

Question 40

Y143 resistance

Answer 40

Raltegravir

Question 41

T66I resistance

Answer 41

EVG

Question 42

Q151

69SSS

Answer 42

Multi-NRTI