 |
|
based on interassay variation of control, but current interpretations use either biologic thresholds based on the normal distribution of wild-type virus from untreated patients or, for most drugs, clinical thresholds based on data from clinical trials (Table 2-14).
|
|
|
| Drug |
Mutations
selected |
Comments |
| Nucleoside Reverse Transcriptase Inhibitors (NRTIs): RT gene mutations |
| AZT |
41L, 67N, 70R,
210W, 215Y/F,
219Q/E |
Thymidine analog mutations (TAMs): reduce
susceptibility to all NRTIs. Most frequent TAMs are 41L,
210W, 215Y, which have greatest impact on NRTI
susceptibility. 67N, 70R, 219Q/E also decrease
susceptibility, but to lesser degree. 184V increases AZT
susceptibility and reduces the emergence of TAMs. 44D
and 118I further decrease susceptibility when present
with TAMs. TAMs infrequently coexist with 65R. |
| d4T |
41L, 67N, 70R,
210W, 215Y/F,
219Q/E |
Most d4T resistance is due to TAMs (see AZT) 65R
causes low-level resistance, occasionally selected by
d4T. 75T/M/A seen infrequently. |
| 3TC |
65R,184V/I |
184V/I: high-level 3TC resistance, with increase in activity
of AZT, d4T, and TDF, and partial reduction of resistance
due to TAMs. Reduces susceptibility to ddl, ABC, though
not clinically significant with 184V/I alone. 44D and 118I
not selected by 3TC, but they confer moderate 3TC
resistance. 65R not selected by 3TC, but can cause
intermediate resistance to 3TC. |
| FTC |
65R,184V/I |
Similar or identical to 3TC. |
| ddI |
65R, 74V |
TAMs confer ddI resistance, with degree of resistance
depending on TAM pathway and number of TAMs. 74V
or 65R mutations alone or combined with 184V/I are
associated with ddI resistance and cross-resistance to
ABC (74V, 65R) and TDF (65R). |
| ABC |
65R, 74V,
115F, 184V |
Resistance with 65R or 74V, increased if 184V/I also
present. 74V more commonly selected by ABC then 65R.
TAM-mediated resistance depends on number of TAMs
and TAM-pathway. 184V/I alone does not confer clinically
significant resistance but further decreases susceptibility
in combination with TAMs or ABC mutations. |
| TDF |
65R, 70E |
Reduced activity with 65R or with ≥3 TAMs that include
41L and 210W. 184V/I increases TDF activity, partially
compensating for 65R or TAMs. 70E uncommon, but
reduces TDF susceptibility. |
Multi -
nucleoside
resistance:
Q151M
compex |
151M plus
62V, 75I, 77L,
116Y |
Uncommon with 3TC- or FTC-containing regimens.
Occurs with or without TAMs. The 151M "complex"
confers high-level resistance to AZT, d4T, ABC, ddI,
intermediate resistance to TDF, and low-level resistance
to 3TC, FTC. |
|
| (continued) |
|
TABLE 2-10::