Zidovudine treatment increased the expression of cytokeratin 10, PCNA and cyclin A. Conversely, cytokeratin 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. Zidovudine treatment, even when applied at 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 potentially be developed as a model for studying the effects of HIV and highly active antiretroviral therapy in vitro. An estimated 33.4 million people are infected with HIV world-wide [1]. The advent of antiviral drugs has greatly decreased mortality from this virus BMS-907351 in vivo and improved the life expectancy of HIV-infected patients. Highly PLX4032 in vivo active antiretroviral therapy

(HAART), which consists of therapy with a combination of reverse transcriptase inhibitors and protease inhibitors, is able to greatly reduce the HIV viral load of patients and help to restore their immune function. However, continuous drug regimens and the patients’ ability to live longer with a suppressed immune system have led to complications. Oral complications are very common in HIV-positive patients. The incidence of the oral complications oral candidiasis and oral hairy leukoplakia has been shown to drop significantly in patients on much HAART [2-4]. Other oral complications that are common in HIV-positive patients, such as Kaposi’s sarcoma and oral aphthous ulceration, have been shown to be unaffected by HAART [2, 3, 5]. Long-term use of

HAART has been associated with increases in the rates of many complications, including oral warts [2, 5], erythema multiforme [6, 7], xerostomia [6, 7], toxic epidermal necrolysis, lichenoid reactions [7, 8], exfoliative cheilitis [6], oral ulceration and paraesthesia [6, 9]. Such adverse oral complications greatly affect the quality of life of patients on HAART, leading to noncompliance with drug regimens. This in turn results in interrupted dosing schedules and suboptimal levels of exposure to the drugs. Nonadherence to a strict drug regimen could eventually lead to drug resistance and compromise future therapy [10]. Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine [ZDV; formerly azidothymidine (AZT) or 3'-azido-3'-deoxythymidine], were first approved by the US Food and Drug Administration for use against HIV/AIDS in 1987 [11]. ZDV has become an essential component of HAART and has a two-pronged antiviral effect. It disrupts the virus both by incorporating itself into viral DNA and by inhibiting the viral reverse transcriptase [11]. ZDV also exhibits some affinity for cellular polymerases [12, 13].