Does iatrogenic scleroderma due to injection-site reaction to enfuvirtide impair absorption of the drug?
BACKGROUND
Chronic iatrogenic scleroderma is a possible obstacle to the absorption of subcutaneously administered drugs. This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV.


METHODS
Fourteen patients treated with an enfuvirtide-based antiretroviral regimen for a median of 45 weeks were enrolled and their ISRs were evaluated. Twelve patients with evidence of ISRs underwent cutaneous biopsies using a 4-mm punch. The maximum plasma enfuvirtide concentration (Cmax) and the area under the enfuvirtide concentration-time curve (AUC) were assessed using blood sampling.


RESULTS
Four different macroscopic patterns of ISR were identified: A--no evidence of cutaneous lesions; B--transient infiltrative lesions that auto-resolved within 24 hours; C--transient nodular lesions that auto-resolved within 7-15 days; and D--stable lesions after more than 30 days. Histological examination showed three morphological patterns: (1) acute urticaria/vasculitis-like pattern, (2) subacute pattern and (3) chronic scleroderma-like pattern. No differences among patients with the various patterns of ISRs were observed, except for a higher Cmax and AUC in patients with pattern 1.


CONCLUSIONS
These results confirm that although iatrogenic scleroderma is not related to impaired enfuvirtide absorption, higher Cmax and AUC values are observed in patients with urticaria/vasculitis-like patterns.
Maggi
Paolo
P
Clinica delle Malattie Infettive, University of Bari, Bari, Italy. p_maggi@yahoo.com
Filotico
Raffaele
R
Bonora
Stefano
S
Volpe
Anna
A
Bellacosa
Chiara
C
Cinori
Eliana
E
de Requena
Daniel Gonzalez
DG
D'Avolio
Antonio
A
Di Perri
Giovanni
G
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D007049:Iatrogenic Disease; D007275:Injections, Intravenous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012594:Scleroderma, Localized / Q000139:chemically induced* / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D014581:Urticaria / Q000473:pathology; D014657:Vasculitis / Q000473:pathology
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D000077560:Enfuvirtide