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.
AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Laboratoire de Virologie, Paris F-75018, France. diane.descamps@bch.aphp.fr
Diane
D
Descamps
Lambert
L
Assoumou
Bernard
B
Masquelier
Anne-Geneviève
AG
Marcelin
Souhila
S
Saidi
Catherine
C
Tamalet
Jacqueline
J
Cottalorda
Jean-Christophe
JC
Plantier
Brigitte
B
Montes
Jacques
J
Izopet
Gilles
G
Peytavin
Sabine
S
Yerly
Véronique
V
Schneider
Constance
C
Delaugerre
Virginie
V
Ferré
Annick
A
Ruffault
Coralie
C
Pallier
Laurence
L
Morand-Joubert
Marie-Laure
ML
Chaix
Vincent
V
Calvez
Françoise
F
Brun-Vézinet
Dominique
D
Costagliola
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