HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide
Descamps, Diane ; Assoumou, Lambert ; Masquelier, Bernard ; Marcelin, Anne-Geneviève ; Saidi, Souhila ; Tamalet, Catherine ; Cottalorda, Jacqueline ; Plantier, Jean-Christophe ; Montes, Brigitte ; Izopet, Jacques ; Peytavin, Gilles ; Yerly, Sabine ; Schneider, Véronique ; Delaugerre, Constance ; Ferré, Virginie ; Ruffault, Annick ; Pallier, Coralie ; Morand-Joubert, Laurence ; Chaix, Marie-Laure ; Calvez, Vincent ; Brun-Vézinet, Françoise ; Costagliola, Dominique
In: Journal of Antimicrobial Chemotherapy, 2008, vol. 62, no. 3, p. 451-455
Aggiungi alla tua lista- Summary
- 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