TABLE 8.

Synergy/additivity of lersivirine with agents from other antiretroviral classes in vitro^a

Agent (n)	Class	Mean vol ± SD (μM2%) of lersivirine:
		Synergy	Antagonism	Combined effect
Abacavir (3)	NRTI	90.6 ± 26.5	−49.3 ± 84.2	Moderate synergy (minor antagonism)
Didanosine (4)	NRTI	156.0 ± 66.1	−3.7 ± 7.3	Strong synergy
Emtricitabine (4)	NRTI	140.5 ± 57.1	−5.1 ± 8.9	Strong synergy
Lamivudine (4)	NRTI	175.1 ± 81.1	−6.3 ± 12.1	Strong synergy
Tenofovir (3)	NRTI	115.6 ± 40.7	−10.8 ± 11.9	Strong synergy
Zidovudine (3)	NRTI	177.5 ± 183.8	−15.4 ± 26.7	Strong synergyb
Atazanavir (2)	PI	6.6 ± 9.4	−23.1 ± 32.6	Additive
Lopinavir (2)	PI	29.1 ± 19.4	−28.5 ± 30.3	Minor synergy/minor antagonismc
Ritonavir (2)	PI	12.6 ± 0.6	−19.1 ± 27.1	Additive
Elvitegravir (3)	INT	69.7 ± 66.5	−20.1 ± 34.8	Moderate synergy
Raltegravir (2)	INT	34.6 ± 13.8	−10.7 ± 15.1	Minor synergy
Enfuvirtide (3)	Entry	75.1 ± 77.8	−32.8 ± 56.8	Moderate synergy (minor antagonism)

^aExperiments performed using a cytopathic-effect-based assay with HIV-1 NL4-3 in MT-2 cells. Volumes of synergy (μM²%) were calculated at 95% confidence intervals using drug combination data from three to four replicate plates per assay, with the aid of MacSynergy II software. Volumes are expressed as means from two to four independent experiments (± standard deviations [SD]). For these studies, synergy (assigned a positive value) or antagonism (assigned a negative value) was defined as drug combinations yielding mean volumes in excess of 25 μM²%. Moderate synergistic/antagonistic activity and strong synergistic/antagonistic activity were defined as mean volumes between 50 and 100 μM²% and in excess of 100 μM²%, respectively. Additive drug interactions were defined by mean volumes of 0 to 25 μM²%. Elvitegravir is an investigational integrase inhibitor (INT).

^bStrong synergy seen in two experiments; additive interaction in the third experiment.

^cMinor synergy/minor antagonism seen in one experiment; additive interaction in the second experiment.