Background Human immunodeficiency virus (HIV) positive patients taking antiretroviral drugs, including protease inhibitors have shown a significant increase in the development of oral complications, a major health issue for those patients. The effect of these drugs on oral epithelium growth and differentiation is presently unknown. In this study, we explore for the first time, the effect of HIV protease inhibitor Amprenavir on gingival epithelium growth and differentiation. Methods Organotypic (raft) cultures of gingival keratinocytes were established. Raft cultures were treated with a range of Amprenavir concentrations. Hematoxylin and eosin staining was performed to examine the effect of Amprenavir on gingival epithelium growth and stratification. Further, raft cultures were immunohistochemically analyzed to determine the effect of Amprenavir on the expression of key differentiation and proliferation markers including cytokeratins, PCNA and cyclin A. Results Amprenavir severely inhibited the growth of gingival epithelium when the drug was present throughout the growth period of the tissue. When drug was added at day 8, Amprenavir treatments altered the proliferation and differentiation of gingival keratinocytes. Expression of cytokeratins 5, 14, 6, 10, PCNA and cyclin A was increased, and their expression pattern was also altered over time in treated rafts. Therefore, biochemically the tissue exhibited characteristics of increased proliferation in the suprabasal layers of Amprenavir treated tissue. Conclusions Our results suggest that Amprenavir treatments deregulated the cell cycle/proliferation and differentiation pathways resulting in abnormal epithelial repair and proliferation. Our system could be developed as a potential model for studying HIV/ highly active antiretroviral therapy (HAART) affects in vitro.

Posaconazole (Noxafil (Schering-Plough Corporation) is a triazole antifungal approved in the United States for the treatment of oropharyngeal candidiasis and for the prophylaxis of Candida and Aspergillus infections in the immunocompromised host. Posaconazole is available only as an oral suspension. When used for the prevention of Candida and Aspergillus infections, posaconazole should be taken three times daily with a high fat meal to maximize oral absorption. Failure to take posaconazole with food will lead to subtherapeutic serum levels and decreased clinical effectiveness of the drug.We report the case of a 49-year-old woman with acute myeloid leukemia who received 4 months of posaconazole as an outpatient for the labeled indication of prophylaxis of Candida and Aspergillus infections. During her last admission, the patient presented with an invasive sinus infection diagnosed as a mixed Aspergillus and Mucor etiology. The patient succumbed to this infection five weeks after presentation. Upon investigation it was found that the patient did not self-administer posaconazole as required in the product labeling, which may have led to drug failure in this patient. We submit this case to illustrate the importance of patient education regarding proper administration of posaconazole. The important role of the outpatient physician, nurse, and pharmacist in this setting is underscored.

Oral complications associated with immunodeficiency virus (HIV) with antiretroviral drugs are becoming a mounting concern in HIV patients. Protease inhibitors have been shown to change the proliferation and differentiation state of oral tissues but the effect of nucleoside inhibitors is currently unknown. This study examines the effect of Zidovudine, also known as AZT, on the growth and differentiation of gingival epithelium. Methods Gingival keratinocytes Organotypic (raft) cultures were established. Raft cultures were treated with a range of Zidovudine concentrations. Hematoxylin and eosin staining was performed to examine the effect of Zidovudine on gingival epithelium growth and stratification. Raft cultures were immunohistochemically analyzed to determine the effect of this drug on the expression of key differentiation and proliferation markers including cytokeratins and PCNA. Results Zidovudine dramatically changed the proliferation and differentiation state of gingival tissues both when it was present throughout the growth period of the tissue and when it was added to established tissue at day 8. Zidovudine treatment increased the expression of cytokeratin 10, PCNA and cyclin A. Conversely, cytokeratins 5, involucrin and cytokeratin 6 expression was decreased. The tissue exhibited characteristics of increased proliferation in the suprabasal layers as well as an increased fragility and an inability to heal itself. Conclusions Zidovudine treatments, even when applied in low concentrations for short periods of time, deregulated the cell cycle/proliferation and differentiation pathways resulting in abnormal epithelial repair and proliferation. Our system could be developed as a potential model for studying HIV/ highly active antiretroviral therapy affects in vitro.