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JAC Advance Access published online on June 13, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn225
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide

Diane Descamps1,2,3,*, Lambert Assoumou4,5, Bernard Masquelier6, Anne-Geneviève Marcelin5,7, Souhila Saidi4,5, Catherine Tamalet8, Jacqueline Cottalorda9, Jean-Christophe Plantier10, Brigitte Montes11, Jacques Izopet12, Gilles Peytavin13, Sabine Yerly14, Véronique Schneider15, Constance Delaugerre16,17, Virginie Ferré18, Annick Ruffault19, Coralie Pallier20, Laurence Morand-Joubert5,21, Marie-Laure Chaix16,17, Vincent Calvez5,7, Françoise Brun-Vézinet1,2,3, Dominique Costagliola on behalf of the ANRS AC-11 Resistance Study Group4,5,22

1 AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Laboratoire de Virologie, Paris F-75018, France 2 Université Denis Diderot-Paris 7, Paris, France 3 INSERM U552, Paris, France 4 INSERM UMR_S 720, F-75013 Paris, France 5 UPMC Univ 06 UMR_S 720, Paris F-75013, France 6 CHU de Bordeaux, Laboratoire de Virologie, Université Victor Segalen Bordeaux 2, EA 2968, Bordeaux F-33076, France 7 AP-HP, Groupe Hospitalier Pitié-Salpétrière, Service de Virologie, Paris F-75013, France 8 Fédération de Microbiologie Hospitalière, CHU Timone, Marseille, France 9 Laboratoire de Virologie, CHU Nice, France 10 Laboratoire de Virologie, GRAM EA2656, Faculté de Médecine-Pharmacie, CHU de Rouen, Rouen, France 11 Laboratoire de Virologie, CHU Montpellier, France 12 Laboratoire de Virologie, CHU Toulouse, France 13 AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Pharmacie, Paris F-75018, France 14 Hôpital de Genève, Laboratoire de Virologie, Genève, Switzerland 15 AP-HP, Hôpital Tenon, Service de Virologie, Paris F-75020, France 16 AP-HP, Hôpital Necker-Enfants Malades, Service de Bactério-Virologie, Paris F-75015, France 17 Université René Descartes, Paris 5, Paris, France 18 Laboratoire de Virologie CHU Nantes, Nantes, France 19 Laboratoire de Virologie CHU Rennes, Rennes, France 20 AP-HP, Hôpital Bicêtre, Service de Microbiologie, Le Kremlin Bicêtre F-94275, France 21 AP-HP, Hôpital Saint-Antoine, Laboratoire de Virologie, Paris F-75012, France 22 AP-HP, Groupe Hospitalier Pitié-Salpétrière, Service de Maladies Infectieuses et Tropicales, Paris F-75013, France

Received 28 February 2008; returned 9 April 2008; revised 7 May 2008; accepted 12 May 2008

* Correspondence address. Laboratoire de Virologie, Groupe Hospitalier Bichat-Claude Bernard, 46 rue Henri Huchard, Paris F-75018, France. Tel: +33-1-4025-6150; Fax: +33-1-4025-6769; E-mail: diane.descamps{at}bch.aphp.fr

Objectives: We studied gp41 mutations associated with failing enfuvirtide salvage therapy.

Methods: This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2.

Results: Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm3, respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment.

Conclusions: Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell count.

Key Words: HIV drug resistance , resistance mutations , gp41 , T-20


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