TABLE 4.
Antiviral activity of ISL and comparator molecules against a panel of HIV-1 variants with mutations in RT in a multiple cycle assay with 10% NHSa
| HIV-1 variant | ISL |
TDF |
AZT |
3TC |
FTC |
|||||
|---|---|---|---|---|---|---|---|---|---|---|
| IC50 (nM) (n)b | FCc | IC50 (nM) (n)b | FCc | IC50 (nM) (n)b | FCc | IC50 (nM) (n)b | FCc | IC50 (nM) (n)b | FCc | |
| WT | 0.80 ± 0.08 (11) | 1 | 45.99 ± 11.56 (16) | 1 | 9.99 ± 1.38 (16) | 1 | 849.86 ± 265.52 (6) | 1 | 291.28 ± 47.80 (17) | 1 |
| M41L | 1.65 ± 0.11 (7) | 2.1 | 97.16 ± 12.88 (8) | 2.1 | 19.82 ± 2.50 (10) | 2 | 1,481.14 ± 301.45 (8) | 1.7 | 370.94 ± 54.58 (8) | 1.3 |
| K65R | 0.34 ± 0.06 (6) | 0.4 | 492.20; 580.36 (2) | 11.6 | 7.79; 9.42 (2) | 0.9 | 4,590.35; 4,787.03 (2) | 5.5 | NA | NA |
| L74I | 1.08 ± 0.09 (5) | 1.4 | 89.50 ± 25.02 (6) | 1.9 | 20.83 ± 3.42 (7) | 2.1 | 2280.97 ± 285.92 (5) | 2.7 | 576.15 ± 86.19 (8) | 2 |
| A114S | 1.74 ± 0.31 (4) | 2.2 | 2.89 ± 2.01 (6) | 0.1 | 4.67 ± 0.28 (7) | 0.5 | 715.56 ± 84.49 (4) | 0.8 | 217.75 ± 24.97 (8) | 0.7 |
| M184I | 8.50 ± 0.59 (7) | 10.6 | 44.96 ± 1.87 (4) | 1 | 8.68 ± 0.55 (4) | 0.9 | >42,016.67 (6) | >49.4 | >42,016.67 (4) | >144.2 |
| M184V | 9.89 ± 0.93 (7) | 12.4 | 48.09 ± 10.38 (4) | 1 | 9.40 ± 1.07 (4) | 0.9 | >42,016.67 (7) | >49.4 | >42016.67 (8) | >144.2 |
| T215Y | 1.99 ± 0.33 (7) | 2.5 | 192.86 ± 13.04 (3) | 4.2 | 82.79 ± 8.07 (6) | 8.3 | 4,045.70 ± 715.99 (5) | 4.8 | 1184.01 ± 135.29 (7) | 4.1 |
| A114S/M184V | 28.25 ± 6.93 ( 8) | 35.3 | 1.81 ± 0.38 (8) | 0.04 | 2.39 ± 0.40 (11) | 0.2 | >42,016.67 (10) | >49.4 | >42,016.67 (12) | >144.2 |
| M41L/A114S/M184V | 32.25 ± 6.20 (4) | 40.3 | 1.98 ± 0.25 (4) | 0.04 | 3.82 ± 0.38 (4) | 0.4 | >42,016.67 (4) | >49.4 | >42,016.67 (4) | >144.2 |
| M41L/L210W/T215Y | 2.95 ± 0.13 (4) | 3.7 | 271.97 ± 26.11 (4) | 5.9 | 73.80 ± 12.01 (4) | 7.4 | 1,796.43 ± 249.18 (3) | 2.1 | 764.22 ± 84.02 (7) | 2.6 |
| D67N/K70R/T215F/K219Q | 3.05 ± 0.43 (7) | 3.8 | 192.94 ± 7.21 (3) | 4.2 | 78.19 ± 12.79 (5) | 7.8 | 4,099.30 ± 508.53 (3) | 4.8 | 3,354.82 ± 218.48 (4) | 11.5 |
| D67N/K70R/A114S/T215F/K219Q | 2.72 ± 0.44 (6) | 3.4 | 3.51 ± 0.40 (7) | 0.1 | 6.73 ± 1.09 () | 0.7 | 969.34 ± 77.79 (3) | 1.1 | 646.52 ± 138.82 (7) | 2.2 |
a
3TC, lamivudine; AZT, zidovudine; FC, fold change; FTC, emtricitabine; HIV-1, human immunodeficiency virus type 1; IC50, half maximal inhibitory concentration; ISL, islatravir; NA, not available; TDF, tenofovir disoproxil fumarate; WT, wild-type.
b
IC50 (half maximal inhibitory concentration; nM) displayed as geometric mean ± standard deviation.
c
Fold change (FC) is calculated as (IC50 against mutant isolate) / (IC50 against WT) for each test article.