TABLE 3.

Mean synergy and antagonism volumes for pairwise combination studies performed between BI 224436 and HIV antiviral inhibitors^a

Inhibitor class and drug	Volumeb (nM2%; ±SD)		Combination effect
	Synergy	Antagonism
NRTI
Lamivudine	39 ± 7.4	−5.8 ± 3.2	Additive
Abacavir	12 ± 5.6	−44 ± 28	Minor antagonism
Zidovudine	26 ± 26	−14 ± 15	Additive
Tenofovir	124 ± 18	−5.1 ± 4.1	Synergy
Emtricitabine	19 ± 5.0	−0.36 ± 0.63	Additive
Didanosine	15 ± 19	−4.3 ± 6.4	Additive
Stavudine	17 ± 15	−9.0 ± 6.6	Additive
NNRTI
Nevirapine	0.2 ± 0.3	−12 ± 13	Additive
Efavirenz	20 ± 16	−4.7 ± 4.1	Additive
Etravirine	43 ± 70	−12 ± 13	Additive
Protease inhibitor
Amprenavir	72 ± 51	−12 ± 12	Moderate synergy
Atazanavir	72 ± 33	−26 ± 23	Moderate synergy
Darunavir	25 ± 18	−24 ± 10	Additive
Indinavir	24 ± 24	−19 ± 17	Additive
Lopinavir	4.6 ± 8.0	−12 ± 20	Additive
Nelfinavir	67 ± 33	−30 ± 10	Moderate synergy
Ritonavir	42 ± 48	−28 ± 12	Additive
Saquinavir	3.4 ± 3.0	−16 ± 22	Additive
Tipranavir	37 ± 34	−17 ± 3.9	Additive
Integrase inhibitor
Raltegravir	11 ± 12	−5.9 ± 7.9	Additive
Dolutegravir	23 ± 44	−12 ± 14	Additive
Entry inhibitors
Maraviroc	19 ± 11	−3.2 ± 4.9	Additive
Enfuvirtide	4.5 ± 1.4	−5.9 ± 6.3	Additive

^aResults are mean synergy and antagonism volumes at 95% confidence intervals, as calculated by MacSynergy II software, for pairwise combination studies performed between BI 224436 and HIV antiviral inhibitors. Mean volumes were calculated based on a minimum of three separate experiments. Cytotoxicity assays were performed in parallel at the highest drug concentrations tested, and no increase in cytotoxicity was observed in drug combinations with BI 224436.

^bMean synergy volumes at 95% confidence (in nM²%) are described at the following levels: >100, strong synergy; 50 to 100, moderate synergy; 25 to 50, minor amount of synergy; 25 to −25, additive; −25 to −50, minor amount of antagonism; −50 to −100, moderate antagonism; and <−100, strong antagonism.