HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide.
OBJECTIVE
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/mm(3), 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.
Descamps
Diane
D
AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Laboratoire de Virologie, Paris F-75018, France. diane.descamps@bch.aphp.fr
Assoumou
Lambert
L
Masquelier
Bernard
B
Marcelin
Anne-Geneviève
AG
Saidi
Souhila
S
Tamalet
Catherine
C
Cottalorda
Jacqueline
J
Plantier
Jean-Christophe
JC
Montes
Brigitte
B
Izopet
Jacques
J
Peytavin
Gilles
G
Yerly
Sabine
S
Schneider
Véronique
V
Delaugerre
Constance
C
Ferré
Virginie
V
Ruffault
Annick
A
Pallier
Coralie
C
Morand-Joubert
Laurence
L
Chaix
Marie-Laure
ML
Calvez
Vincent
V
Brun-Vézinet
Françoise
F
Costagliola
Dominique
D
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D018791:CD4 Lymphocyte Count; D000077560:Enfuvirtide; D005260:Female; D005602:France; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics*; D016879:Salvage Therapy; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D019562:Viral Load
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide