January 3, 2008
The NYU Bluestone Center for Clinical Research is actively engaged in an exciting study examining the effectiveness and safety of administering a topical drug for the treatment of oral warts.
The investigators are examining the use of natural human interferon alpha (IFNα) administered by the oral mucosal route in the treatment of oral warts in HIV-seropositive subjects receiving combination anti-retroviral therapy.
In this study, safety and efficacy will be determined by a combination of objective and subjective assessments, in order to develop a global overview of this novel and potentially therapeutic drug.
It is well known that viral lesions of the mouth in subjects infected with the human immunodeficiency virus (HIV) are common, and may be indicative of disease progression. One of the most common causes of oral lesions is the human papillomaviruses (HPV), a group of DNA viruses which induce a host of hyperplastic lesions in the oral soft tissues (e.g., papillomas, warts, condylomata and focal epithelial hyperplasia). Oral warts due to HPV infection generally conform to one of three clinical presentations: cauliflower, spiky or flat.
Although introduction of Highly-Active Anti-Retroviral Therapy (HAART) has reduced the frequency of many secondary infections in HIV disease, there has been an increase in the occurrence of oral warts. It has also been suggested that there is a link of increased occurrence of oral warts and HAART. Based on a 2001 retrospective study on 1280 HIV-infected patients, it was been reported that the prevalence of oral warts was highest among the patients who were being treated with HAART (23%) compared to those without medication (5%) and those who were being treated with other antiretroviral therapy (15%). While HPV infection has been identified as the most significant risk factor in the development of malignant anogenital lesions, the development of malignant oral lesions in association with HPV infection has not been demonstrated consistently. Even though the threat of malignancy has not been conclusively established, oral warts do cause a significant reduction in quality of life due to their harmful affects on appearance and potential for causing discomfort during routine activities such as eating and talking. Current treatments include physical interventions such as cryosurgery, electrocoagulation, CO2 laser and excision; however, the rate of recurrence is high.
Interferon was identified in 1957 as a mediator of viral interference. They are proteins derived from different cell types in response to many stimuli including viruses, bacteria, foreign cells, macromolecules, and other chemical compounds. In addition to their antiviral activities, interferons have potent immunomodulating effects. Most commonly, IFNα is used via injection or intraveneously, and it is approved for clinical use in the USA for condyloma acuminata AIDS-related Kaposi's sarcoma, hairy cell leukemia, chronic myelogenous leukemia, malignant melanoma, chronic hepatitis B and chronic hepatitis C.
This study will use a topical formulation of Interferon (natural human interferon alpha or IFNα) to treat the oral warts. Although oral ingestion is not generally used as a route of administration for IFN because of the concern for rapid inactivation by digestive enzymes and the lack of detectable IFN in the bloodstream after oral (ingestion) administration, the biologic activity of low-dose IFNα by oral mucosal administration has demonstrated important biological responses even when given in very low doses. A previous open-label pilot study with 15 HIV-seropositive males with multiple oral warts treated with combination antiretroviral chemotherapy and orally-dissolved IFNα lozenges showed positive results at week 16. In the subjects who showed positive response, defined as ≥10% reduction in total surface area involved by warts, IFNα treatment was continued up to week 40. A dramatic reduction in total surface area of warts was discovered in many of the subjects who continued treatment up to week 40. During 40 weeks of treatment there were no serious adverse events reported among these subjects. The pilot study concluded that IFNα used topically could be well tolerated.
For these reasons, NYU is conducting a larger and more powerful study to determine the safety and efficacy of IFNα treatment delivered via the oral mucosal route for HIV-infected patients with oral warts who are also receiving anti-viral therapies.
The NYU Bluestone Center for Clinical Research is still enrolling patients eligible for this study. If interested, please call 212-998-9310.