TABLE 4.
Cross resistance to other NRTIs and resistance reversal in viruses selected with d4T in vitro
| Recombinant and passage | RT genotype | IC50, μM (fold change) fora:
|
|||||
|---|---|---|---|---|---|---|---|
| ABC | ddI | 3TC | Tenofovir | ddC | AZT | ||
| RD 01 | |||||||
| p0 | 215C | 1.44 (0.8) | 4.59 (0.8) | 1.88 (0.9) | 0.87 (0.9) | 0.66 (0.8) | 0.035 (1.3) |
| p6 | V75I, C215Y, H481Y | 2.91 (1.7) | 7.8 (1.3) | 6.42 (3.1) | 0.82 (0.8) | 1.44 (1.7) | 0.050 (1.9) |
| RD 02 | |||||||
| p0 | 210W, 215C | 1.93 (1.1) | 4.85 (0.8) | 3.01 (1.5) | 0.82 (0.8) | 0.99 (1.2) | 0.03 (1.1) |
| p6 | 210W, C215Y | 3.03 (1.8) | 6.52 (1.1) | 4.06 (2.0) | 1.16 (1.2) | 1.06 (1.2) | 0.29 (11) |
| RD 03 | |||||||
| p0 | 41L, 210W, 215C | 2 (0.9) | 4.73 (0.8) | 2.39 (0.6) | 1.02 (1.0) | 0.78 (0.6) | 0.037 (1.9) |
| p5 | 41L, 210W, 215C, K65R | 4.27 (1.9) | 9.1 (1.6) | 29.6 (7.7) | 2.07 (2) | 2.36 (1.7) | 0.023 (1.2) |
| p8 | 41L, 210W, C215Y, K65R | 5.37 (2.4) | 9.47 (1.7) | 43.6 (11) | 2.18 (2.2) | 2.83 (2.1) | 0.033 (1.7) |
| RD 04 | |||||||
| p0 | 210W, 215D | 1.51 (0.9) | 5.98 (1.0) | 3.6 (1.7) | 0.64 (0.7) | 0.93 (1.1) | 0.016 (0.6) |
| p6 | 210W, 215D, K65R | 3.6 (2.1) | 10.9 (1.8) | 38.8 (19) | 1.58 (1.6) | 2.45 (2.9) | 0.011 (0.4) |
| RD 05 | |||||||
| p0 | 41L, 215D | 1.83 (0.8) | 5.45 (1.0) | 5.95 (1.6) | 0.68 (0.7) | 1.22 (0.9) | 0.02 (1.0) |
| p5 | 41L, 215D, K65R | 3.5 (1.6) | 9.35 (1.7) | 27.5 (7.2) | 1.21 (1.2) | 2.9 (2.1) | 0.016 (0.8) |
| p6 | 41L, D215Y, K65R | 4.14 (2.4) | 10.5 (1.8) | 36.8 (18) | 1.68 (1.7) | 2.11 (2.5) | 0.02 (0.7) |
| HXB2215D | |||||||
| p0 | 215D | 1.27 (0.7) | 5.1 (0.9) | 3.9 (1.9) | 0.35 (0.4) | 0.99 (1.2) | 0.005 (0.2) |
| p6 | 215D, K65R | 4.09 (2.4) | 12.5 (2.1) | 31.63 (15) | 1.29 (1.3) | 2.85 (3.3) | 0.01 (0.4) |
| RD 22wt | |||||||
| p0 | 1.12 (0.6) | 4.61 (0.8) | 1.79 (0.9) | 0.56 (0.6) | 0.69 (0.8) | 0.014 (0.5) | |
| p6 | K65R, M202I | 4.18 (2.4) | 12.5 (2.1) | 26.5 (13) | 2.11 (2.2) | 2.88 (3.4) | 0.02 (0.7) |
| p0K65Rb | K65R | 3.39 (1.5) | 10.3 (1.5) | 19.2 (7.2) | 1.7 (1.6) | 2.52 (2.6) | 0.01 (0.4) |
| RD 23wt | |||||||
| p0 | 1.78 (1.0) | 4.52 (0.8) | 2.13 (1.0) | 0.84 (0.9) | 0.84 (1.0) | 0.02 (0.7) | |
| p6 | K65R | 4.87 (2.8) | 8.8 (1.5) | 22.4 (11) | 1.76 (1.8) | 2.09 (2.4) | 0.014 (0.5) |
| p0K65Rb | K65R | 4.50 (1.9) | 12.5 (1.6) | 28.9 (11) | 2.18 (1.9) | 2.7 (2.9) | 0.012 (0.4) |
| HXB2wt | |||||||
| p0 | 1.36 (0.8) | 4.56 (0.8) | 2.39 (1.2) | 0.48 (0.9) | 0.89 (1.0) | 0.007 (0.3) | |
| p7 | V75A, K65R | 3.43 (2.0) | 13.6 (2.3) | 21.1 (11) | 1.19 (1.2) | 2.35 (3.5) | 0.009 (0.4) |
| HXB265Rb | K65R | 3.45 (2.0) | 11.5 (2.0) | 16.9 (8.8) | 1.12 (1.2) | 2.21 (3.3) | 0.007 (0.3) |
| HXB265R/215Yb | K65R, T215Y | 3.35 (2.0) | 11.2 (1.9) | 29.3 (15) | 1.07 (1.1) | 2.51 (3.7) | 0.008 (0.3) |
| HXB2215Yb | T215Y | 1.74 (1.0) | 6.72 (1.2) | 4.46 (2.3) | 0.52 (0.5) | 1 (1.5) | 0.015 (0.6) |
a
Values in parentheses are changes in drug susceptibility compared to the IC50 value of the reference WT NL4-3 isolate used in the PhenoSense assay. In boldface are indicated the isolates that had evidence of reduced susceptibility using the assay cutoff values of the PhenoSense assay. ABC, abacavir.
b
Mutations were introduced by site-directed mutagenesis.