 |
 TABLE 2-11:
|
Nucleoside and Nucleotide Analog Resistance Mutations by Category (Continued)
|
|
| Mutation Category |
Mutation |
Comments |
Multinucleoside
resistance
mutations |
T69
insertion |
Selected by thymidine analogs, but rare in HAART era,
especially with 3TC- or FTC-containing regimens. Causes
high-level resistance to all NRTIs and TDF. |
Multinucleoside
resistance
mutations |
Q151M
complex |
Selected by thymidine analogs, but rare in HAART era,
especially with 3TC- or FTC-containing regimens. Causes
high-level resistance to all NRTIs when combined V75I,
F77L, F116Y. TDF may retain activity. |
| d4T mutation |
V75T/M/
A |
Selected by d4T in vitro and results in decreased d4T
susceptibility, but uncommon with clinical use of d4T. |
| ABC mutation |
Y115F |
Selected by ABC, resulting in ~3-fold decrease in ABC
susceptibility. |
|
TABLE 2-12: |
Non-nucleoside Reverse Transcriptase Inhinitor (NNRTI) Resistance Mutations
|
|
| Mutation |
Comments |
| A98G |
Selected by NVP (uncommon), resulting in minimal decrease in NVP
susceptibility. Associated with decreased ETR susceptibility in
combination with other ETR mutations. |
| L100I |
Causes intermediate resistance to DLV, NVP, and EFV. Usually occurs
with K103N, resulting in further loss of NNRTI susceptibility especially to
EFV and DLV. Associated with decreased ETR susceptibility in
combination with other ETR mutations. Increases susceptibility to AZT and
possibly d4T. |
| K101E/P |
K101E: Selected by NVP and EFV (uncommon), resulting in intermediatelevel
resistance to NVP and DLV, and low-level resistance to EFV. K101P:
Associated with intermediate resistance. to DLV, NVP, and EFV, but
usually occurs in combination with K103N, resulting in high-level
resistance. K103E/P is associated with decreased ETR susceptibility in
combination with other ETR mutations. |
| K103N/S/R |
K103N: Commonly selected by all NNRTIs, resulting in high-level
resistance to DLV, NVP, EFV. Does not affect ETR susceptibility. K103S
less common, resulting in lower degree of resistance to DLV and EFV, but
moderate resistance to NVP. K103R: Polymorphism with minimal effect
on NNRTI susceptibility, unless combined with V179D. |
| V106M/A |
V106M: Selected by NVP (common with subtype C), resulting in high-level
resistance to DLV, NVP, and EFV. Does not affect ETR susceptibility.
V106A: Selected by NVP (uncommon), resulting in high-level NVP
resistance, intermediate DLV resistance, and low-level EFV resistance.
V106I was considered a polymorphism that does not cause NNRTI
resistance; however, in the DUET studies it was associated with
decreased ETR susceptibility in combination with other ETR mutations. |
| V108I |
Selected by NVP and EFV (uncommon), resulting in minimal decrease in
DLV, NVP and EFV susceptibility. Does not affect ETR susceptibility. |
|
|
