TABLE 6.

Susceptibilities of Env-recombinant NL4-3 molecular clones created from maraviroc-resistant CC1/85 by SDM to entry inhibitors in PBL

Clonej	Mutation in gp120a						Entry inhibitor susceptibility in PBLb
	Domain V2	Domain V3			Domain C3	Domain V4	Maraviroc		Aplaviroc IC50 (nM)	Enfuvirtide IC50 (nM)
	Amino acid 163	Amino acid 316	Amino acid 319	Amino acid 323	Amino acid 355	Amino acid 405	IC50 (nM)	Plateau (%)c
MVCres	K	T	A	V	Y	A	>333	NDRi	0.23	5.78
MVCres(TAI)	K	T	A	I	Y	A	0.35	67d	0.13	3.28
MVCres(AAV)	K	A	A	V	Y	A	0.41	74d	0.32	9.29
MVCres(AAI)	K	A	A	I	Y	A	0.50	95	0.23	10.1e
MVCsensh	T	A	A	I	N	S	0.89f	93f	0.53f	12.2g

^aThe 2.56-kb Env gene was cloned by PCR from maraviroc-resistant variants of CC1/85 and inserted into pNL4-3, to produce MVCres. A similar fragment was cloned from the start virus to produce MVCsens. SDM was performed on the MVCres clone to revert mutations in the V3 loop back to the wild type.

^bDrug susceptibility was assessed over 7 days in PBL. Viral replication was quantified by p24. Results shown are the geometric means of five experiments unless otherwise stated.

^cPercent inhibition for the plateau in maximal inhibition.

^dP < 0.05 versus MVCsens (analysis of variance).

^eGeometric mean of four experiments.

^fGeometric mean of three experiments.

^gGeometric mean of two experiments.

^hThere were an additional eight amino acid differences in gp41 between MVCsens and MVCres.

ⁱNDR, no dose response (see Fig. 3A).

^jBoldface letters in clone designations indicate amino acid substitutions in MVCres.