TABLE 1.
Isolatea | Mutation(s) in proteaseb
|
Mutation in the following cleavage sites:
|
FC in IC50 compared to that for WTc
|
RC (% of that for WT) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Amino acid at position 84 | Other mutations | p7/p1 | p1/p6 | NFV | SQV | IDV | RTV | APV | LPV | ATV | ||
A1 | I84A | L10I, M46I, L63H, A71V, V77I | A431V | WT | 600 | 1,000 | 73 | 60 | 32 | 10 | 38 | 41 |
A2 | I84A | L33F, M46I, L63P | NA | NA | 600 | 141 | 27 | 85 | 31 | NA | NA | NA |
A3 | I84A | L10I, M46L, L63T, A71V | NA | NA | 600 | 365 | 78 | 76 | 43 | 11 | NA | 22 |
A4 | I84A | L10F, M46I, L63P, A71V | WT | L449F | 600 | 241 | 58 | 42 | 32 | 14 | NA | 2.5 |
A5 | I84A | L10V, M46I, L63A/P, A71V | A431V | L449Q | 600 | 256 | 53 | 54 | 28 | 9.0 | NA | 18 |
A6 | I84A | L10I, M46I, L63P, A71V, L76V | A431V | WT | 64 | 24 | 38 | 34 | 21 | 14 | NA | 1.0 |
A7 | I84A | L10F, L19I, M46I, I47V, I54V, L63P, A71V | A431V | S451I | 600 | 1,000 | 92 | 141 | 74 | 124 | NA | NA |
A8 | I84A | L10V, K20I, M36I, M46I, A71V, G73S, L76V | A431V | WT | 600 | 265.5 | 400 | 86 | 252 | 94 | NA | 6.4 |
A9 | I84A | L10I, M46I, L63P, A71V, V77I | WT | L449F | 600 | 1,000 | 138 | 167 | 33 | 16 | 52 | 64 |
A10 | I84A | L10F, K20I, M46I, I54M, L63P, A71V, G73T, V77I | A431V | L449L/V, R452R/K | 600 | 1,000 | 400 | 400 | 400 | 59 | 700 | 27 |
A11 | I84A | L10F, M46I, L63P, A71A/V, V77V/I | A431A/V | L449F | 600 | 1,000 | 73 | 73 | 47 | 14 | 63 | 31 |
A12 | I84A | L10I, L33F, M46I, I54V, L63P, A71V, L76V | A431V | L449L/Q, S451T | 600 | 1,000 | 400 | 400 | 400 | 210 | 25 | 16 |
A13 | I84A | L10F, K20I, M36M/I, M46I, I54V, L63P, A71V, G73S | WT | R452S | 196 | 1,000 | 178 | 400 | 43 | 50 | 700 | 5.7 |
A14 | I84A | L10I, M46I, I47V, L63P, A71V, L76V | A431V | WT | 210 | 69 | 152 | 105 | 141 | 104 | 21 | 0.7 |
A15 | I84A | L10I, K20R, M36I, M46I, I54V, Q58E, L63A/T, A71V, V82V/I | A431V | WT | 600 | 1,000 | 118 | 400 | 30 | 75 | 253 | 22 |
Median | 600 | 1,000 | 92 | 86 | 43 | 33 | 57 | 18 | ||||
C1 | I84C | WT | WT | 15 | 6.1 | 1.2 | 1.6 | 1.7 | 0.4 | NA | 12.0 | |
C2 | I84C | K20I, M36I, V82I | WT | S451N | 59 | 14 | 1.3 | 8.6 | 5.4 | NA | NA | 11.0 |
C3 | I84C | L10I, L19L/I, L24I, L63H | WT | L449L/F | 74 | 56 | 4.1 | 10 | 8.6 | 1.6 | NA | 8.9 |
C4 | I84C | L10F, L19L/V, L24I, M46L, L63P | A431V | L449F | 395 | 92 | 11 | 9.1 | 10 | 3.1 | NA | 0.6 |
C5 | I84C | L10L/I, K20R, M36I, M46L, L63P, V82IV/I | WT | WT | 51 | 41 | 3.8 | 15 | 20 | 3.1 | NA | 15.0 |
C6 | I84C | L10I, G16A, M46I, L63P, L76V | A431V | WT | 144 | 24 | 63 | 22 | 64 | 47 | NA | 13.0 |
C7 | I84C | L10I, L24I, M46L, L63P, A71T, G73S, V771 | A431A/V | L449F | 600 | 1,000 | 42 | 60 | 23 | 7.2 | NA | 1.2 |
C8 | I84C | L10I, L19I, K20K/R, L24L/I, M46I, K55K/R, L63P | WT | WT | 86 | 68 | 6.4 | 14 | 12 | 2.9 | NA | 38 |
C9 | I84C | L10V, L24L/I, M46L, I54L, L63P | WT | WT | 70 | 115 | 5.5 | 20 | 30 | 2.3 | 9.1 | NA |
C10 | I84C | L10I, K20T, Q58E, V82I | WT | WT | 286 | 242 | 5.5 | 29 | 53 | 5.1 | 19 | 64 |
C11 | I84C | L10I, L24I, L63H | WT | WT | 91 | 121 | 5.7 | 15 | 18 | 2.8 | 5.0 | 25 |
Median | 86 | 68 | 5.5 | 15 | 18 | 3.0 | 9.1 | 13 |
Except for the patient from whom isolate A1 was obtained, the treatment histories of the patients from which the isolates were obtained are unknown.
Reference sequences were compared with baseline sequences. Polymorphisms at the following positions are not listed: 12, 13, 14, 15, 18, 33 (other than L33F), 35, 37, 39, 41, 43, 45, 57, 60, 61, 62, 64, 65, 66, 67, 69, 70, 72, 74, 83, 89, 91, 93, and 95. Samples with a mixture of sequences at a particular codon were excluded from the analysis.
The current reduced susceptibility cutoffs are 2.5 for RTV, 3.6 for NFV, 2.3 for SQV, 10 for IDV, 4.0 for APV, and 9 for LPV-RTV. For calculation purposes FC values representing 50% inhibitory concentrations (IC50s) higher than the maximum measurable level were assigned an arbitrary value, based on the ratio between the highest drug concentration tested and the reference virus 50% inhibitory concentration: 600 for NFV, 1,000 for SQV, 400 for IDV and APV, 700 for ATV. NA, not available.