TABLE 5.
Antiviral efficacy results for MK-4965 in combination with 18 FDA-approved antiretroviral compounds in CEM-SS or MAGI-CCR5 cellsa
| Compound class and compoundb | Mean synergy vol/antagonism vol (nM2%, μM2%, or nMμM%)c | Antiviral effect |
|---|---|---|
| NRTIs | ||
| 3TC | 27.9/−3.75 | Nonantagonistic |
| ABC | 47.0/−10.9 | Nonantagonistic |
| AZT | 76.5/−12.6 | Nonantagonistic |
| d4T | 19.1/−6.74 | Nonantagonistic |
| ddC | 12.5/−4.46 | Nonantagonistic |
| ddI | 45.1/−4.07 | Nonantagonistic |
| FTC | 17.0/−0.52 | Nonantagonistic |
| TDF | 22.6/−4.88 | Nonantagonistic |
| Tenofovir DF | 40.5/−7.49 | Nonantagonistic |
| NNRTIs | ||
| DLV | 19.2/−4.43 | Nonantagonistic |
| EFV | 29.5/−1.50 | Nonantagonistic |
| ETR | 14.6/−1.24 | Nonantagonistic |
| NVP | 28.2/−19.6 | Nonantagonistic |
| PIs | ||
| DRV | 35.8/−2.14 | Nonantagonistic |
| IDV | 19.4/−0.08 | Nonantagonistic |
| Entry inhibitors | ||
| MVC | 6.22/−24.3 | Nonantagonistic |
| ENF | 23.8/−2.16 | Nonantagonistic |
| Integrase strand transfer inhibitor (RAL) | 24.6/−3.38 | Nonantagonistic |
| d4T-RBV (positive control) | ||
| CEM-SS cells | 3.80/−311 | Highly antagonistic |
| MAGI-CCR5 cells | 0.53/−591 | Highly antagonistic |
a
The 95% confidence intervals around the experimental dose-response surface were used to evaluate the data statistically.
b
Studies of the antiviral efficacy of MK-4965 in combination with MVC were performed with MAGI-CCR5 cells. All other evaluations were performed with CEM-SS cells.
c
The antiviral synergy plot (95%) data sets from multiple experiments (n = 3) were combined, and the arithmetic means were calculated for each drug-drug concentration. The positive and negative values are individually summed to give the mean volumes for synergistic and antagonistic interactions, respectively.