Dynamics of enfuvirtide resistance mutations in enfuvirtide-experienced patients remaining in virological failure under salvage therapy

Abstract

Background: Evaluation of the dynamics of enfuvirtide (ENF) resistance mutations after ENF withdrawal in patients with virological failure under salvage therapy may be helpful to optimize the management of ENF in human immunodeficiency virus (HIV)-infected patients. Methods: Seven patients with a failing ENF-containing regimen, initiated for at least 3 months (median 6.4 months, range 3–14), were included and followed up prospectively at the time of virological failure. Genotypic analysis of the gp41 region by bulk sequencing and clonal analysis was performed in plasma and/or peripheral blood mononuclear cells to detect ENF resistance mutations. Results: Genotypic profiles of ENF-resistant variants at ENF discontinuation were as follows: V38A in 3 patients, V38A+N42T+N43D in 1 patient, N43D in 2 patients, and N43K in 1 patient. Clonal analysis showed that maintaining ENF treatment after virological failure has an impact on both (1) the number of resistance profiles detected, and (2) the time of persistence of ENF-resistant variants. ENF-resistant variants were archived in HIV DNA in 5/7 patients. At 1 month after ENF withdrawal, no significant increase in HIV-1 viral load was observed. Conclusion: The persistence of ENF-resistant variants was found to be correlated to exposure time to failing drug. ENF withdrawal should be considered in patients with virological failure to preserve the possible efficacy of ENF recycling or upcoming entry inhibitors.

Keywords::

• HIV
• enfuvirtide
• resistance
• archiving

Declaration of interest: The authors have no commercial, or other associations that might pose a conflict of interest (e.g., pharmaceutical stock ownership, consultancy advisory board membership, relevant patents, research funding). This work was supported by the Roche Laboratory and the Assistance Publique-Hôpitaux de Paris.