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JAIDS Journal of Acquired Immune Deficiency Syndromes:
BASIC SCIENCE: PDF Only

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

Roman, François; Gonzalez, Dimitri; Lambert, Christine; Deroo, Sabrina; Fischer, Aurélie; Baurith, Thérèse; Staub, Thérèse; Boulmé, Ronan; Arendt, Vic; Schneider, François; Hemmer, Robert; Schmit, Jean-Claude

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Abstract

Summary: 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.

(C) 2003 Lippincott Williams & Wilkins, Inc.

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