title: A prospective clinical and pathological examination of injection site reactions with the HIV-1 fusion inhibitor enfuvirtide.
abstract: OBJECTIVE
  Antiretroviral regimens containing the fusion inhibitor enfuvirtide (ENF) are associated with sustained viral suppression and immunological benefit. However, local injection site reactions (ISR) occur in the majority of patients. The aim of this study was to determine the pathogenesis of ISRs.
  
  
  METHODS
  Injection sites were evaluated prospectively from 30 min up to 15-30 days post-injection in ENF-experienced (Cohort I) and ENF-naive patients (Cohort II) during the first 2 weeks of therapy. Four to five injections were given in rotating abdominal sites by a nurse using a standardized technique and were rigorously evaluated.
  
  
  RESULTS
  Reactions were observed in 80-100% of patients; the majority of the reactions were mild to moderate, generally appeared within 24-48 h post-injection, and pain, induration and erythema were the most common clinical signs. Whereas most patients experienced ISRs, the overall prevalence in Cohort II was low (35% maximum). Punch biopsies of injection sites in Cohort I consisted primarily of mixed lymphocytic infiltrates with eosinophils and neutrophils. Injection vehicle (ENF buffer minus ENF) and reduced volume (2 x 0.5 ml ENF [45 mg] versus 1.0 ml [90 mg] ENF) were investigated in Cohort II. Fewer reactions appeared with vehicle and pain was absent with the smaller injection volume. Pathology was indistinguishable between ENF, vehicle and normal tissue in Cohort II patients.
  
  
  CONCLUSIONS
  These results suggest that injection technique, injection volume and peptide may influence ISR to ENF.
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Myers
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Selim
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McDaniel
authors.forename: Russell
authors.initials: R
authors.lastname: Hall
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: John A
authors.initials: JA
authors.lastname: Bartlett
authors.forename: Andrea L
authors.initials: AL
authors.lastname: True
mesh_terms: D000005:Abdomen / Q000473:pathology; D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D007274:Injections, Intraperitoneal / Q000009:adverse effects*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide