HIV Resistance mutations Flashcards

1
Q

M184V - Affected class

A

NRTI

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2
Q

M184V - high level resistance (2)

A

3TC (lamivudine)

FTC (emtricitabine)

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3
Q

M184V - low level resistance (2)

A

ddI (didanosine)

ABC (abacavir)

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4
Q

M184V - Increased susceptibility (3)

A

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

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5
Q

M184V - mechanism

A

Decreases NRTI incorporation

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6
Q

Thymidine analog mutations (TAMs) - Resistance (2)

A

ZDV (zidovudine)

d4T (stavudine)

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7
Q

TAMs mildly resistance (3)

A

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

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8
Q

TAM mechanism

A

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

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9
Q

Needed for high-level ABC and ddI resistance

A

M184V and 3+ TAMs

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10
Q

M41L
L210W
T215Y

A

Type I TAMs

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11
Q

D67N
K70R
T215F
K219Q/E

A

Type II TAMs

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12
Q

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

A

Resistance to all NRTIS

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13
Q

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

A

ABC
ddI
TDF

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14
Q

K65R Resistance

A

All NRTI except ZDV

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15
Q

K65R - Increased susceptibility (1)

A

ZDV

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16
Q

L74V - Intermediate resistance (2)

A

ddI

ABC

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17
Q

L74V - Slight increase susceptibility (2)

18
Q

NNRTI Resistance mechanisms

A

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

19
Q

Primary NNRTI resistance mutations

A
K103N/S
V106A/M
Y181C/I/V
Y188L/C/H
G190A/S/E
E138K
20
Q

K103N resistance

A

EFV (efavirenz)

NVP (Nevirapine)

21
Q

V106

A

Resistance to DRV

22
Q

T69 insertion selected by

23
Q

T69 insertion high level resistance

A

Tenofovir
ABC
DDI

24
Q

T69 insertion decreased susceptibility (2)

25
Q151m selected by
DDI | ZDV
26
Q151M High level resistance
ABC DDI Thymidine analogs
27
Q151 low level resistance
3tc FTC Tenofovir
28
K103N high level resistance
EFV NVP (Rilpivirine and etravirine susceptible)
29
Y181C selected by
Nevirapine
30
Y181C resistance (one high level, 3 low) | What NNRTI still works?
High level R nevirapine Decreased susceptibility to EFV, RPV, ETV) Doravirine still works (only)!
31
E138K selected by
RPV
32
E138K resistance
Decreased susceptibility to RPV, ETR, causes failure with K101E
33
Q148R selected by
RAL | EVG
34
Q148R resistance
High level to Raltegravir, elvitegravir Also R to bic and dtg Increase dolutegravir to bid if present
35
N155H resistance
High level resistance to RAL, EVG Decreased DTG and BIC if Q148R also present
36
I50L selected by
Atazanavir
37
I50L resistance
High level Atazanavir Increase suspect. Other PIs
38
Y188L selected by
NVP, EFV | +/- DOR
39
Y188L Resistance
NVP, EFV | +/- DOR
40
Y143 resistance
Raltegravir
41
T66I resistance
EVG
42
Q151 | 69SSS
Multi-NRTI