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.
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.
Authors: Mark Nelson; Keikawus Arastéh; Bonaventura Clotet; David A Cooper; Keith Henry; Christine Katlama; Jacob P Lalezari; Adriano Lazzarin; Julio S G Montaner; Mary O'Hearn; Peter J Piliero; Jacques Reynes; Benoit Trottier; Sharon L Walmsley; Calvin Cohen; Joseph J Eron; Daniel R Kuritzkes; Joep Lange; Hans-Jürgen Stellbrink; Jean-François Delfraissy; Neil E Buss; Lucille Donatacci; Cynthia Wat; Lynn Smiley; Martin Wilkinson; Adeline Valentine; Denise Guimaraes; Ralph Demasi; Jain Chung; Miklos P Salgo Journal: J Acquir Immune Defic Syndr Date: 2005-12-01 Impact factor: 3.731
Authors: Antonio D'Avolio; Mauro Sciandra; Daniel Gonzalez de Requena; Allende Ibañez; Stefano Bonora; Giovanni Di Perri Journal: Ther Drug Monit Date: 2006-02 Impact factor: 3.681
Authors: Adriano Lazzarin; Bonaventura Clotet; David Cooper; Jacques Reynes; Keikawus Arastéh; Mark Nelson; Christine Katlama; Hans-Jürgen Stellbrink; Jean-François Delfraissy; Joep Lange; Les Huson; Ralph DeMasi; Cynthia Wat; John Delehanty; Claude Drobnes; Miklos Salgo Journal: N Engl J Med Date: 2003-05-29 Impact factor: 91.245
Authors: Jacob P Lalezari; Keith Henry; Mary O'Hearn; Julio S G Montaner; Peter J Piliero; Benôit Trottier; Sharon Walmsley; Calvin Cohen; Daniel R Kuritzkes; Joseph J Eron; Jain Chung; Ralph DeMasi; Lucille Donatacci; Claude Drobnes; John Delehanty; Miklos Salgo Journal: N Engl J Med Date: 2003-03-13 Impact factor: 91.245