|
|
|
 TABLE 2-10:
|
Resistance Mutations (Continued)
|
|
| Drug |
Mutations
selected |
Comments |
Multi -
nucleoside
resistance:
T69
insertion |
69 insertion
41L, 62V, 70R,
210W, 215Y/F,
219Q/E |
Uncommon with 3TC- or FTC-containing regimens.
Usually occurs with TAMs, conferring high-level
resistance to all NRTIs including TDF. |
Multi -
nucleoside
resistance:
multiple
TAMs |
41L, 67N, 70R,
210W, 215Y/F,
219Q/E |
Most common cause of multinucleoside resistance.
Only AZT and d4T select for TAMs. 44D and 118I
further decrease NRTI susceptibility. |
| Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): RT gene mutations |
| NVP |
100I, 103N,
106A/M, 108I,
181C/I,
188C/L/H, 190A |
181C is favored mutation with NVP unless combined
with AZT, in which case 103N favored. 103N, 106M,
188L/C cause high-level NVP resistance. 188H causes
low-level NVP resistance. |
| DLV |
103N, 106M,
181C, 188L,
236L |
Some NNRTI mutations (190A/S, 225) decrease
susceptibility to NVP and EFV but cause DLV
hypersusceptibility (see Table 2-13); clinical significance
unknown. |
| EFV |
100I, 103N,
106M, 108I,
181I/C, 188L,
190S/A, 225H |
103N is favored mutation with EFV, causing high-level
NNRTI resistance. 188L and 106M also cause highlevel
EFV resistance. Although 181C (and some other
NNRTI mutations) cause only low-level EFV resistance
phenotypically, response to EFV is generally poor, and
other NNRTI mutations may be present in subpopulations. |
| ETR |
90I, 98G, 100I,
10IE/P, 106E,
179D/F/T,
181C/I/V,190A/S |
Poor response to ETR-based therapy in patients with >
ETR mutations.Mutations 179D/F/T, 181V or 190S at
baseline show reduced response. The 181C mutation
has no impact unless other mutations are present. The
103N mutation has no effect on activity. |
|
| Drug |
Major
mutations |
Minor mutations |
Comments |
| Protease Inhibitors (PIs): Protease gene mutations |
IDV and
IDV/r |
46I/L,
82A/F/T,
84V |
101/F/I/R/V, 20M/R,
24I, 32I, 36I, 54V,
71V/T, 73S/A, 76V,
77I, 90M |
At least 3 mutations required for
resistance to unboosted IDV (>4-fold
decrease in susceptibility). |
| NFV |
30N, 90M |
10F/I, 36I, 46I/L,
71V/T, 77I,
82A/F/T/S, 84V,
88D/S |
30N most common mutation, causing no PI cross-resistance. 90M occurs in some (especially non-B subtypes), causing greater PI cross-resistance. |
SQV
and
SQV/r |
48V, 90M |
10I/R/V, 24I, 54L/V,
62V, 71V/T, 73S,
77I, 82A/F/T/S, 84V |
With unboosted SQV 90M is typically first mutation, then 48V. 48V is unique to SQV, but 90M causes PI cross-resistance. Selection of PI mutations is unlikely with SQV/r in PI-naïve patients. |
|
| (continued) |
|
 |
