TABLE 2.
Analysis of two-drug combinations at fixed concentration ratios by use of the Loewe additivity model
| Drug combination | Molar ratio | CI valuea at level of HCMV inhibition of: |
CIwtb | Overall result | ||
|---|---|---|---|---|---|---|
| 50% | 75% | 90% | ||||
| Letermovir + GCV | 1:166 | 0.90 ± 0.22 | 0.83 ± 0.13 | 0.90 ± 0.25 | 0.88 | Additive |
| 1:500 | 1.03 ± 0.08 | 1.00 ± 0.11 | 1.09 ± 0.27 | 1.05 | ||
| 1:1,500 | 1.00 ± 0.05 | 1.06 ± 0.06 | 1.15 ± 0.09 | 1.09 | ||
| Letermovir + CDV | 1:16.6 | 1.21 ± 0.18 | 1.18 ± 0.05 | 1.18 ± 0.07 | 1.18 | Additive |
| 1:50 | 1.19 ± 0.25 | 1.19 ± 0.18 | 1.22 ± 0.14 | 1.20 | ||
| 1:150 | 1.01 ± 0.30 | 1.08 ± 0.14 | 1.19 ± 0.04 | 1.12 | ||
| Letermovir + FOS | 1:8,333 | 1.15 ± 0.36 | 1.18 ± 0.18 | 1.30 ± 0.01 | 1.23 | Additive/minor antagonism |
| 1:25,000 | 1.25 ± 0.14 | 1.35 ± 0.03 | 1.49 ± 0.20 | 1.40 | ||
| 1:75,000 | 1.15 ± 0.11 | 1.20 ± 0.09 | 1.28 ± 0.17 | 1.23 | ||
| Letermovir + ACV | 1:1,666 | 1.09 ± 0.13 | 0.86 ± 0.16 | 0.83 ± 0.20 | 0.89 | Additive |
| 1:5,000 | 1.18 ± 0.24 | 1.04 ± 0.11 | 0.97 ± 0.05 | 1.03 | ||
| 1:15,000 | 1.19 ± 0.16 | 1.21 ± 0.11 | 1.26 ± 0.12 | 1.23 | ||
a
CI values were determined for the indicated two-drug combinations at 50%, 75%, and 90% inhibition of HCMV replication according to the method described by Chou and Talalay (34) using the CalcuSyn program (Biosoft, Ferguson, MO, USA). CIs of <0.8, 0.8 to 1.2, or >1.2 indicate synergism, additive effect, and antagonism respectively.
b
The CIwt value was assigned as follows: (CI50 + 2CI75 + 3CI90)/6. Datasets from at least 3 independent experiments were combined, and arithmetic means ± standard deviations were calculated for each drug-drug combination.