HIV Resistance mutations Flashcards
M184V - Affected class
NRTI
M184V - high level resistance (2)
3TC (lamivudine)
FTC (emtricitabine)
M184V - low level resistance (2)
ddI (didanosine)
ABC (abacavir)
M184V - Increased susceptibility (3)
ZDV (zidovudine)
d4T (stavudine)
TDF (tenofovir)
M184V - mechanism
Decreases NRTI incorporation
Thymidine analog mutations (TAMs) - Resistance (2)
ZDV (zidovudine)
d4T (stavudine)
TAMs mildly resistance (3)
ABC (abacavir)
ddI (didanosine)
TDF (tenofovir)
TAM mechanism
Enhanced removal of incorporated NRTI by promoting phosphorolytic reaction that leads to primer unblocking
Needed for high-level ABC and ddI resistance
M184V and 3+ TAMs
M41L
L210W
T215Y
Type I TAMs
D67N
K70R
T215F
K219Q/E
Type II TAMs
4+ Of 41, 67, 70, 210, 215, 219
Resistance to all NRTIS
What drugs to Type I TAMs cause cross-resistance to? (3)
ABC
ddI
TDF
K65R Resistance
All NRTI except ZDV
K65R - Increased susceptibility (1)
ZDV
L74V - Intermediate resistance (2)
ddI
ABC
L74V - Slight increase susceptibility (2)
ZDV
TDF
NNRTI Resistance mechanisms
NNRTIs inhibit reverse transcriptase by binding hydrophobic pocket close but not contiguous with RT active site, mutations are within pockets or adjacent residues
Primary NNRTI resistance mutations
K103N/S V106A/M Y181C/I/V Y188L/C/H G190A/S/E E138K
K103N resistance
EFV (efavirenz)
NVP (Nevirapine)
V106
Resistance to DRV
T69 insertion selected by
DDI
D4t
T69 insertion high level resistance
Tenofovir
ABC
DDI
T69 insertion decreased susceptibility (2)
3tc
FTC