Interruption of enfuvirtide in HIV-1 infected adults with incomplete viral suppression on an enfuvirtide-based regimen.
Many antiretroviral drugs continue to exert an anti-human immunodeficiency virus (HIV) benefit in the presence of drug resistance mutations. The degree to which enfuvirtide exerts continued antiviral activity in the presence of incomplete viral suppression has not been defined. To address this question, 25 subjects interrupted enfuvirtide while remaining on a stable background regimen. Enfuvirtide interruption was associated with an immediate but limited increase in plasma HIV-1 RNA levels. Enfuvirtide resistance waned rapidly in the absence of drug pressure and was no longer detectable by week 16 in most individuals. These data indicate that enfuvirtide has measurable antiviral activity in the setting of incomplete viral suppression. Although enfuvirtide resistance mutations are associated with significant fitness defects in vivo, the clinical significance of these mutations remains undefined.
Deeks
Steven G
SG
University of California, San Francisco, San Francisco, CA 94110, USA. sdeeks@php.ucsf.edu
Lu
Jing
J
Hoh
Rebecca
R
Neilands
Torsten B
TB
Beatty
George
G
Huang
Wei
W
Liegler
Teri
T
Hunt
Peter
P
Martin
Jeffrey N
JN
Kuritzkes
Daniel R
DR
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide