HIV: Resistance Testing

Question 1

NRTI: K65R

Answer 1

reduced response to TDF and all NRTIs (likely K65E and K65N too) except increased S to AZT; decreases fitness; virus will either go down TAM pathway or K65R pathway (of note, K70E is also a significant TDF mutation)

Question 2

NRTI: T69S (or insertion complex at 69)

Answer 2

pan-NRTI R when present w/ TAM at 41, 210, or 215 (avoid all NRTIs except TDF even if no TAMs present); insertion complex is when 2 or more amino acids are there (usually S and one other, so seen as S-A or S-G); comes as part of the 69 insertion complex that also includes TAMs and others –> M41L, A62V, K70R, L210W, T215Y/F, K219Q/E

Question 3

NRTI: L74V

Answer 3

R to ddI; reduced S to ABC; increased S to AZT and TDF; decreases fitness

Question 4

NRTI: Q151M

Answer 4

R to all NRTIs except TDF

Question 5

NRTI: M184V

Answer 5

decreases fitness; usually first mutation in regimens w/ 3TC or FTC; R to 3TC and FTC; reduced response to ABC if TAMs present; increased S to AZT and TDF; may be hidden and not show up on panel given reduced fitness (consider this if a number of other mutations)

Question 6

NRTI: H208Y

Answer 6

increased S to NVP and EFV

Question 7

NRTI: T215Y

Answer 7

Increased S to NVP and EFV

Question 8

NRTI: TAM1 mutations

Answer 8

M41L, L210W, T215Y

Question 9

NRTI: TAM2 mutations

Answer 9

D67N, K70R, K219E/Q

Question 10

NRTI: TAMs

Answer 10

from exposure to AZT, d4T; reduced response to all NRTIs (especially if 3 or more TAMs or for ABC if M184V and 1 TAM) for TAM1 and all NRTIs but TDF for TAM2; increased S to NNRTIs; virus will either go down TAM pathway or K65R pathway

Question 11

NNRTI: K103N

Answer 11

R to EFV and NVP but not ETR or RPV

Question 12

NNRTI: E138K

Answer 12

R to RVP and some ETR R

Question 13

NNRTI: Y181C/I

Answer 13

R to NVP; reduced response to EFV; moderate/severe impact on ETR

Question 14

PI: V32I

Answer 14

Major LPV; minor DRV, ATV

Question 15

PI: I47V

Answer 15

Major LPV; minor DRV (I47A also major for LPV)

Question 16

PI: I50L or I50V

Answer 16

I50L: major ATV (first mutation to unboosted ATV can increase S to other PIs which is why ATV is a good first regimen); I50V major DRV and minor LPV

Question 17

PI: I54M/L

Answer 17

Major DRV (this and many other I54_ mutations are minor for ATV and LPV)

Question 18

PI: L76V

Answer 18

Major DRV, LPV; may increase ATV S if no other ATV mutations present

Question 19

PI: V82A/F/T

Answer 19

Major LPV, minor ATV (V82I also minor ATV and V82S also major LPV); V82A increases DRV S

Question 20

PI: I84V

Answer 20

Major ATV, DRV, minor LPV

Question 21

PI: N88S

Answer 21

Major ATV

Question 22

INSTI: Y143R/H/C

Answer 22

Major RAL and EVG (usually need a minor mutation too), minor DTG

Question 23

INSTI: Q148H/K/R

Answer 23

Major RAL and EVG (usually need a minor mutation too); DTG will not work if Q148H and N155H present or reduced S if this and at least 2 other minor mutations are present

Question 24

INSTI: G140S

Answer 24

Minor RAL, part of combination that can reduce S to DTG

Question 25

INSTI: N155H

Answer 25

Minor RAL and EVG; DTG will not work if this and Q148R present

Question 26

Pathways of failure if on TDF/FTC

Answer 26

M184V then K65R

Question 27

Pathways of failure if on ABC/3TC

Answer 27

M184V then L74V or K65R

Question 28

NNRTI: L100I

Answer 28

R or reduced S to EFV, NVP, ETR, RPV

Question 29

NNRTI: K101P

Answer 29

R or reduced S to EFV, NVP, ETR, RPV (also K101E for RPV)

Question 30

NNRTI: V106M

Answer 30

R to EFV, NVP, V106 is a minor ETR mutation

Question 31

NNRTI: V108I

Answer 31

R to EFV, NVP