Table 1. Synergy volume of double and triple combinations of antivirals against 2009 H1N1 viruses A/California/04/09 (CA04), A/California/05/09 (CA05), and A/California/10/09 (CA10) as determined by Neutral Red assay.
Regimen | CA04 | CA05 | CA10 |
Double combinations (µg/mL2%) | |||
Zanamivir/Oseltamivir carboxylate | −24±116 | −155±89 | −197±98 |
Zanamivir/Peramivir | −35±112 | −197±108 | −239±93 |
Amantadine/Oseltamivir carboxylate | 112±154 | 133±80 | 135±67 |
Amantadine/Ribavirin | 12±82 | 22±36 | 69±59 |
Ribavirin/Oseltamivir carboxylate | 178±188 | 222±143 | 166±73 |
TCAD at fixed concentrations of amantadine (µg/mL3%) | |||
0.1 µg/mL amantadine | 106±208 | 312±195 | 226±84 |
0.32 µg/mL amantadine | 292±212 | 293±154 | 296±82 |
1.0 µg/mL amantadine | 346±212 | 337±196 | 311±139 |
3.2 µg/mL amantadine | 475±221 | 485±97 | 413±163 |
TCAD at fixed concentrations of ribavirin (µg/mL3%) | |||
0.1 µg/mL ribavirin | 92±119 | 146±82 | 171±137 |
0.32 µg/mL ribavirin | 114±250 | 135±95 | 271±105 |
1.0 µg/mL ribavirin | 179±292 | 478±138 | 353±108 |
3.2 µg/mL ribavirin | 691±144 | 763±256 | 632±216 |
TCAD at fixed concentrations of oseltamivir carboxylate (µg/mL3%) | |||
0.001 µg/mL oseltamivir carboxylate | 66±92 | 104±53 | 153±84 |
0.0032 µg/mL oseltamivir carboxylate | 69±285 | 248±93 | 193±101 |
0.01 µg/mL oseltamivir carboxylate | 359±256 | 583±122 | 442±153 |
0.032 µg/mL oseltamivir carboxylate | 465±291 | 437±355 | 317±164 |
Synergy volumes represent the sum of the synergy or antagonism across all concentrations of two drugs for a double combination, or all concentrations of two drugs at a fixed concentration of the third drug for the TCAD regimen. The concentrations of each drug used are provided in Table S1. Combinations with synergy volumes >100 µg/mL2% for double combinations or >100 µg/mL3% for triple combinations are considered to be strongly synergistic (using the lower 95% confidence interval). Conversely, combinations with synergy volumes <−100 µg/mL2% or µg/mL3% are considered to be strongly antagonistic. Bold numbers denote volumes that are defined as strongly synergistic or antagonistic. Synergy volumes are presented as the mean between replicates with 95% confidence intervals. Typically, between 3 and 6 experiments were run for each combination, with each experiment having 3 replicate wells for each condition.