Resistance

Question 1

M184V/I decreases….

Answer 1

Selects 3TC/FTC and decreases >100 fold
LLR to ABC and DDI

M184I emerges first - more common HIV-1 substitution - overcome by M184V within several weeks

Question 2

M184V/I increases…

Answer 2

Susceptibility to AZT, d4T and TDF

Slows emergence of resistance to these

Question 3

K65R reduces…

Answer 3

TDF, ABC, ddI, d4T - small decrease in sensitivity but enough to stop activity

LLR to FTC and 3TC - larger decrease in sensitivity but not enough to stop activity

More likely to emerge in those with subtype C

Question 4

K65R increases…

Answer 4

AZT susceptibility (except when occurs with Q151M)

Question 5

L100I decreases susceptibility to…

Answer 5

EFV, ETR, RPV - HLR

Occurs in those taking these drugs

NVP - less significant reduction

Question 6

L100I when combined with k103N reduces…

Answer 6

NVP and EFV by >50 fold

Also RPV, ETR and DOR (lesser extent)

Question 7

K101E

Answer 7

Selected in patients receiving each NNRTI
Usually occurs in combination with other NNRTI mutations
Alone - highest effect on NVP, lesser on EFV, ETR, RPV, DOR
(Minimal data re DOR)

Question 8

K101P

Answer 8

More effect than K101E
NVP, EFV, RPV - >50 fold decrease
ETR - 5 fold
DOR - no effect

Question 9

K103N

Answer 9

NVP, EFV > 50 fold

Question 10

V106A

Answer 10

Selected in patients on NVP or DOR
50 fold reduction NVP
5 fold EFV
Intermediate reductions in DOR if alone - if combined with other DOR ass. mutations can cause high level resistance

Question 11

V106M

Answer 11

NVP, EFV - 30 fold reduction

DOR - low/intermediate reductions

Question 12

E138K

Answer 12

Occurs in those on RPV
Alone - 2 fold reduction
With M184 - enough to cause failure on RVP containing regime

Question 13

Y181I/V

Answer 13

HLR NVP
Also reduced susceptibility to ETR, RPV
Variable effect on DOR

Question 14

Y181C

Answer 14

HLR NVP
Also reduces RVP, EFV, ETR
Alone does not appear to reduce DOR susceptibility

Question 15

Y188L/C

Answer 15

L - HLR to NVP, EFV, DOR.

C - HLR to NVP, EFV

Question 16

G190A/S/E

Answer 16

A - HLR NVP, 5-10 fold EFV

S - HLR NVP, EFV

E - HLR NVP, EFV, RPV, ETR, DOR

Question 17

M230L

Answer 17

IR to HLR - all NNRTIs incl DOR

Question 18

T66A/I/K reduces susceptibility to -

Answer 18

All - elvitegravir

K - elvitegravir plus Raltegravir

Question 19

E92Q reduces susceptibility to

Answer 19

ELVITEGRAVIR

Ral to lesser extent

Question 20

E138K/A/T and G140S/A/C

Answer 20

Alone E138 do not reduce INSTI susceptibility
G140 - ELV slight reduction

With Q148 - HLR to RAL and ELV, lesser effect on DTG

Question 21

Y143c/r

Answer 21

Reduce susceptibility to RAL

HLR to RAL if combined with accessory mutations eg t97a

Question 22

S147G

Answer 22

Elvitegravir

Question 23

Q148H/R/K

Answer 23

Reduce susceptibility to RAL and ELV particularly if with accessory mutations

Can also decrease BIC and DTG susceptibility if combined with other mutations eg e138 and g140 and accessory mutations

Question 24

N155H

Answer 24

RAL, ELV

DTG to a lesser extent if combined

Question 25

R263K

Answer 25

Decrease susceptibility to DTG and BIC

Question 26

Baseline testing

Answer 26

For all patients.
Baseline integrate resistance not recommended until background rate of resistance >3% or if history suggestive of transmission from patient with likely or proven insti resistance