TABLE 3.
Phenotypic and genotypic characterization of isolates from 19 subjects
| Patient no. | BL or Rx daya | Protease genotypeb | RT genotypec | Change (n-fold) in IC50
|
|
|---|---|---|---|---|---|
| LPV | NNRTId | ||||
| 1 | BL* | L10I, I54V, L63A, A71V, V82A | No NNRTI mutation | 2.3 | 1.7 |
| 660 | L10(I/V), K20 (K/T), M36 (M/I), M46 (M/I/L), I54V, L63A, A71V, V82A | K103(N/K), G190(G/A) | 24.0 | 555.6 | |
| 2 | BL* | L10F, V32I, M36I, M46L, A71V, V82A | No NNRTI mutation | 5.2 | 8.9 |
| 84* | L10X^, L24I, M36I, M46L, I54V, L63P, V82A | K101(K/Q), K103(K/N), Y181(Y/C) | 20.3 | >85.0 | |
| 140* | L10F, L24I, M36I, M46L, I54V, L63P, V82A | K103(K/N), Y181C | 33.6 | >85.0 | |
| 3 | BL* | L10F, M36V, I54V, L63P, V82A | No NNRTI mutation | 26.0 | 12.3 |
| 867 | L10F, L24I, M36V, M46I, F53(F/L), I54V, R57(R/K), L63P, I64(I/V), V82A | G190A | 59.0 | 182.0 | |
| 4 | BL* | L10X^, L63P, A71V, I84V, L90M | No NNRTI mutation | 2.5 | 2.4 |
| 341* | L10F, E35(D/E), M46I, L63P, K70(R/K), A71V, I84V, L90M | K103N, Y181C | 9.4 | >24.9 | |
| 763 | L10(F/I), L33(L/F), M36(M/I), M46I, I54V, L63P, A71V, I84V, L90M | K103N, Y181C | 37.0 | 461.0 | |
| 922 | L10F, L33F, M46I, I54V, L63P, A71V, I84V, L90M | K103N, Y181C | 67.0 | >625.0 | |
| 5 | BL* | L10I, M36I, L63(A/P), A71V, L90M | No NNRTI mutation | 2.7 | 3.5 |
| 925 | L10I, M36I, I54(I/V), L63(A/P/T), A71V, V82(A/V), L90M | No NNRTI mutation | 1.1 | 0.6 | |
| 6 | BL* | L10(V/I), V32I, I62V, M46I, I47V, L63P, V77I | No NNRTI mutation | 4.5 | 1.3 |
| 1091 | L10(V/I), V32I, M46I, I47A, L63P, V77I, V82(V/I) | K103N | 209 | 197 | |
| 7 | BL* | L10(M/I), M46I, L63P, A71T, V77I, N88S, L90M | K101(K/Q), K103N, G190(G/C) | 0.7 | >22.7 |
| 84* | L10I, M46I, L63P, A71T, V77I, N88G, L90M | K101Q, G190C | 6.5 | >59.5 | |
| 168* | L10I, L33F, M46I, I54(V/I), L63P, A71L, L76V, V77I, N88G, L90M | K101Q, G190C | 23.6 | >59.5 | |
| 337* | L10I, G16(G/A), L33F, M46I, I54V, L63P, A71L, L76V, V77I, N88G, L90M | K101Q, G190C | 46.3 | >24.9 | |
| 501* | L10I, G16A, L33F, M46I, I54V, I62(V/I), L63P, A71L, V82(V/A), N88G, L90M | K101Q, G190C | 90.6 | 52.7 | |
| 8 | BL | L10(V/I), M36I, M46I, L63P, A71V, I84V, L90M | K103N, V106A | 6.2 | 645.2 |
| 330 | L10I, K20(K/R), M36I, M46I, I54V, L63P, A71V, G73S, I84V, L90M | K103N, V106A | 30.0 | 434.8 | |
| 9 | BL | L10I, G48V, I54S, L63P, A71V, V77I, V82A | No NNRTI mutation | 87.0 | 0.2 |
| 339 | L10I, L33(L/F), M46(M/I/V), G48V, I50V, I54S, L63P, A71V, V77I, V82A | K103N, V106A | 218.0 | 434.8 | |
| 10 | BL | V32(V/I), L63P, A71V, V82(V/A) | No NNRTI mutation | 1.6 | 0.5 |
| 168 | M46(M/L), I47(I/V), I54(I/V), L63P, A71V, V82(V/A) | K103(K/N), Y181(Y/C), G190(G/A) | 5.6 | 40 | |
| 11 | BL | V32I, I47V, L63P, V82A | No NNRTI mutation | 2.7 | 0.3 |
| 358 | L10F, V32I, L33F, M46I, I47V, L63P, V82A | K103(N/K), Y181(Y/C), G190(G/A) | 37.0 | 18 | |
| 12 | BL | L10I, M36(M/I), M46I, I54V, L63P, G73(G/C), V82A, L90M | K103(K/N), V106(V/A), Y181(Y/C) | 43.0 | 2 |
| 359 | L10(F/I), T12K, I13(I/V), K20(K/R), L33F, 3bM36I, K43T, M46I, I54V, L63P, I66(I/V), V82A, L90M | K103N, Y181C | 211.0 | 454.5 | |
| 13 | BL | L10(L/I), K20R, M36I, I54(V/I), L63P, V82A | No NNRTI mutation | 13 | 1.1 |
| 268 | L10I, K20R, M36I, R41(R/K), M46I, I54V, L63P, L76(L/V), V82A | K103(K/N), Y181C | 27.0 | 465.1 | |
| 14 | BL | L10(L/I), M46L, I54V, L63P, A71V, V82A | No NNRTI mutation | 13 | 0.6 |
| 339 | L10(L/F/I/V), M46L, I54V, L63P, A71V, V82A | K103(K/I), Y181(Y/C) | 26 | 89 | |
| 15 | BL | L10I, G48V, I54V, L63P, A71V, V77I, V82A, L90M | No NNRTI mutation | 20.0 | 4.7 |
| 336 | L10I, M46(M/I), G48V, I54V, L63P, A71V, V77I, V82A, L90M | K103N | 43.0 | >285.7 | |
| 16 | BL | L10I, M46I, I54V, L63P, A71V, V77I, V82A | No NNRTI mutation | 17.0 | 0.5 |
| 434 | L10I, K14(K/R), L33(L/F), M46I, I54V, L63P, A71V, I72(I/V), V77I, V82A | K101(K/P/Q/T), K103N | 30.0 | >285.7 | |
| 679 | L10I, K14(K/R), L33F, M46I, I54V, L63P, A71V, I72(I/V), V77I, V82(A/S) | K101P, K103(N/S) | 34.0 | 250 | |
| 17 | BL | L10I, I54V, L63P, A71V, V77I, V82T, L90M | No NNRTI mutation | 12.0 | 0.9 |
| 276 | L10F, K20M, E34(E/K), M36(M/I), M46(M/I), I54V, I62(I/V), L63P, A71V, V77I, V82(T/S), L90M | G190S | 23.0 | 104.0 | |
| 506 | L10F, K20(I/M/V), E34K, M36I, I54V, I62V, L63P, H69(H/Q), A71V, V77I, V82S, L90M | G190S | 51.0 | 138.0 | |
| 18 | BL | L10(L/I), K20R, M36I, I54(I/V), L63(L/H), L90M | No NNRTI mutation | 2.8 | 0.3 |
| 112 | L10(L/I), K20R, M36I, I54(A/V), Q61D, A71V, I72R, V82A, L89I, L90M, Q92K | L100(L/I), K103N | 99.0 | >333.3 | |
| 280 | L10(L/I), K20R, V32(V/I), M36I, M46I, I47(I/V), I50(I/V), I54V, K55R, Q61(D/N), A71V, I72R, G73(G/S), V82A, L89(L/F/I/M), L90M, Q92K | L100I, K103N | 149.0 | >333.3 | |
| 427 | L10V, K20R, M36I, M46I, I50V, I54V, K55R, I64(I/L), A71V, I72R, V82A, L89I, L90M, Q92K | L100I, K103N | 252.0 | >285.7 | |
| 19 | BL | L10(I/V), K20(K/R), L33F, M36I, I54V, L63P, A71V, G73(G/S), V82(V/A), I84(I/V), L90M | No NNRTI mutation | 57.0 | 0.7 |
| 111 | L10I, K20R, L33F, F53L, I54V, L63P, A71V, G73S, V82A, L90M | K103N | 121.0 | 128 | |
| 493 | T4(T/P), L10(I/V), K20R, L33F, E34(E/V), M36I, M46(M/I), I47(I/V), F53L, I54V, K55(K/R), L63P, A71V, G73S, V82A, L90M | K101(Q/K), K103N | 177.0 | >285.7 | |
a
BL, baseline sample; Rx, prescription. Asterisk indicates samples tested by Virco, Inc.; all other samples were tested by Virologic, Inc.
b
PI mutations provided in the table include those associated with resistance to LPV (reference 22) and other PIs (reference 15). These include L10(F/I/R/V), K20(M/R), L24I, D30N, V32I, L33F, M36I, M46I, I47V, G48V, I50V, F53L, I54(L/T/V/S), L63P, A71(I/L/T/V), G73(S/A), V77I, V82(A/F/T), I84V, N88(D/S), and L90M. For rebound samples, all new mutations are included. Caret, underlined sequence; ND, not determined. Bold text indicates new mutations.
c
Only NNRTI mutations were included.
d
NNRTIs in the treatment regimen were as follows: for subjects 1 to 14, NVP; for subjects 13 to 19, EFV.