Resistance mutations Flashcards
(25 cards)
M184V
- Most commonly occurring NRTI resistance mutations
- High level (reduces susceptibility 200 fold) to lamivudine and emtricitabine
- Low level resistance to abacavir however if also K65R or L74V then high level resistance
- Associated with reduced virus replication
- Found in up to 1% new diagnosed persons
Most common pattern of NRTI mutations in patients experiencing virological failure on tenofovir and NNRTI based first line treatment
M184V/I alone or M184V/I plus K65R
K65R
- NRTI resistance, intermediate resistance TDF, FTC, ABC, 3TC and increased susceptibility to AZT
- (However NADIA trial showed TDF/3TC still as effective as AZT/3TC even in presence of K65R)
- With M184V also high level resistance to ABC
- More common in Clade C
L74V
- Intermediate resistance to ABC
- More common with M184V and in those with ABC/3TC backbone
Effect of M184V plus TAMS
- Decreases the impact of TAMs on D4T, TFV and AZT
- Enhances the impact of TAMs on ABC and DDI
Classic TAMs (selected by thymidine analogs zidovudine- AZT and stavudine-d4T)
TAM 1 pattern:
M41L
L210W
T215Y
TAM 2 pattern:
D67N
K70R
T215Y/F
K219Q/E
Presence of 3 or more TAMs or K65R
- Reduced susceptibility to 3TC/FTC
- Type 1 TAMS have greater negative impact on virological response to ABC or TDF than type 2 TAMS
Primary NNRTI resistance mutations:
- K101, K103N/S, Y181C/I/V, V106A/M, Y188L/C/H, G190A/S/E, E138K
-> Cause high level resistance to NVP, variable resistance to EFZ - K103N: most commonly transmitted drug resistance mutation
What INSTI resistance might you see in those with Vf on DTG?
- G118R and R263K, associated with 5-10 fold reduced susceptibility to most INSTIs
Most common INSTI mutation seen in persons with virological failure receiving CAB/RPV
Q148HR
G140S/A/C together with Q148H/R/K
Together >100 reduced susceptibility to RAL and EVG, 10 fold CAB, 2-5 fold DTG + BIC
E92Q/G/V
Reduces RAL 5 fold and EVG 30 fold, does not reduce BIC/CAB/DTG
Y143C/R
Selected by RAL and causes reduced RAL susceptibility especially if in combination with T97A
K103N
- Most commonly transmitted drug resistance mutation
- Selected in persons on NVP or EFV (and reduces susceptibility to)
E138K
- Selected in a high proportion of people failing RPV, and smaller proportion receiving ETV, but does not appear to reduce susceptibility to EFV, DOR or NVP
- (often develops with a M184V when failing something with RPV)
3 Common RAL resistance mutations:
- Q148HRK (also most common seen in VF in CAB/RPV)
- N155H (selected by RAL/EVG/DTG/CAB, reduces susceptibility to RAL/EVG with minimal effect on others)
- Y143CR (especially when in combination with T97A)
Failing dolutegravir:
- R263K most common
- N155H seen in a third
- Q1488HRK
Darunavir resistance mutations
- Double dose darunavir with any DRV resistance mutation
Typical resistance patterns on failing NRTI
70% Wild type
NRTI: M184V (3TC/FTC)
Typical resistance pattern failing NNRTI
K103N/Y181C (EFV)
K101/E138K (RPV)
Typical resistance pattern failing INSTI
Q148/N155/Y143 (RAL)
R263K (DTG)
What constitutes a positive result on western blot?
- Presence of bands at at least 2 of the following:
- p24, gp41 and gp120/160
Causes of indeterminate Western blot
o Indeterminate:
Presence of some bands but not meeting criteria
Can occur in early HIV infection, HIV-2, pregnancy or cross reactivity with other antibodies e.g. recent Flu vaccine or autoimmune disorder
Definition of sensitivity
Proportion of true positives that will correctly be identified as positive
