TABLE 2.

ENF susceptibilities of NL4-3/D36G mutants and clinical isolates carrying single substitutions in gp41 amino acid residues 36 to 45

Substitution(s)cData for NL4-3/D36G based virusesaData for primary clinical isolatesb
ENF IC50 (μg/ml)Fold change compared to NL4-3/D36G (parental virus)Baseline ENF IC50 (μg/ml)Treatment ENF IC50 (μg/ml)Fold change compared to baseline virus
NL4-3/D36G (parental virus)0.012
Q40H0.256210.0280.53619
N43D0.210180.0040.996249
N43D0.0131.593123
V38A0.188160.0181.07960
V38E13.21,100d
G36D0.0917.60.0062.701f450
G36D0.0140.24217
G36D0.0030.0134.3
G36E0.47139.30.0190.81143
G36S0.0887.30.0140.4129
G36S0.0410.49912
N43S0.0675.6d
N43K0.0635.30.0270.0853.1
N42T0.0453.8d
L44M0.0211.8d
L45M0.0171.4d
N42Se0.0060.5
  • a Produced by site-directed mutagenesis of NL4-3, altered to match the consensus sequence at amino acid position 36 (aspartic acid replaced by glycine).

  • b On-treatment clinical isolates from trials T20-205 and T20-208 that acquired single amino acid substitutions between amino acids 36 and 45 of gp41 and their paired baseline isolates, which had the consensus sequence indicated in footnote c.

  • c Relative to the consensus wild-type sequence GIVQQQNNLL.

  • d Mutation only observed in recovered on-treatment isolates in combination with another mutation at positions 36 to 45.

  • e N42S is a polymorphism observed in ≈16% of fusion inhibitor-naïve baseline isolates and was not seen as a change during treatment.

  • f The isolate also contained an N-K mixture at position 126 in HR-2 of gp41.