Uncommon mutations at residue positions critical for enfuvirtide (T-20) resistance in enfuvirtide-naive patients infected with subtype B and non-B HIV-1 strains.
Enfuvirtide (T-20) is the lead compound of the new class of antiretroviral drugs called fusion inhibitors. T-20 resistance-associated mutations located in the heptad repeat 1 (HR-1) domain of gp41 have been described in vitro and in clinical trials. In this study, the authors investigated the primary genotypic T-20 resistance in subtype B and non-B HIV-1 strains from patients at the beginning of their follow-up in the Luxembourg HIV Cohort as well as the emergence of primary resistance to T-20 in patients who had long-term infection with subtype B HIV-1 strains. HR-1 fragments including the gp41 amino acid 36-45, T-20-sensitive region were screened for amino acid variation. No classic T-20 resistance-associated mutations were identified in subtype B or non-B isolates. However, several uncommon mutations were found at residues 37, 39, and 42 for subtype B isolates and at residue 42 for a subtype non-B isolate. The results indicate that primary genotypic T-20 resistance seems to be rare in HIV-1, regardless of subtype or prior antiretroviral therapy (excluding fusion inhibitors). However, episodic variation within HR-1 can occur and needs further phenotypic evaluation in accurate fusion inhibitor resistance assays.
Roman
François
F
Retrovirology Laboratory, Centre de Recherche Public-Santé, Biomedical Information Unit, Centre Hospitalier de Luxembourg, 4 rue Barblé, L-1210 Luxembourg. roman.f@retrovirology.lu
Gonzalez
Dimitri
D
Lambert
Christine
C
Deroo
Sabrina
S
Fischer
Aurélie
A
Baurith
Thérèse
T
Staub
Thérèse
T
Boulmé
Ronan
R
Arendt
Vic
V
Schneider
François
F
Hemmer
Robert
R
Schmit
Jean-Claude
JC
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000627:therapeutic use*; D016415:Sequence Alignment; D013997:Time Factors
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D000077560:Enfuvirtide