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November 21, 2006
Imiquimod for Anal Intraepithelial Neoplasia? (Reuters Health)
Clinicians in Germany report that treatment with imiquimod usually clears human papillomavirus (HPV)-related anal intraepithelial neoplasia (AIN), without having to resort to surgical or ablative treatments, in HIV-positive men.
Even with HAART, the prevalence of AIN and anal cancer has not decreased among HIV-infected men who have sex with men (MSM). AIN is usually treated with surgical excision -- which causes significant morbidity, such as stenosis or incontinence -- or with ablative treatments that have high recurrennce rates.
Dr. Alexander Kreuter, at Ruhr University Bochum, and associates had previously reported successful results using topical imiquimod treatment to treat AIN among 10 HIV-positive men.
Imiquimod is a topical immune response modifier approved in the US for treatment of anogenital warts, superficial basal cell carcinoma, and actinic keratoses. It binds to the Toll-like receptor 7 on monocytes, macrophages and dendritic cells, which induces proinflammatory cytokines, thereby activating innate- and T helper 1-immune responses.
For their current report, published in the Archives of Dermatology for November, Dr. Kreuter's team conducted a prospective, open-label pilot study in 28 HIV-positive MSM with histologically confirmed AIN. At the start of the trial, all carried high-risk HPV types.
Patients were treated with 5% imiquimod cream applied overnight three times a week for 16 weeks, during which time they were requested to refrain from receptive anal intercourse.
Twenty-two patients complied with treatment, and 17 experienced a complete clinical and histologic response, although long-term clearance of HPV was rare. Response to treatment was not affected by the grade or the localization of AIN.
All the compliant patients experienced erythema, four reported flu-like symptoms during the first 2 weeks, seven developed mild erosions, and one had severe erosions resulting from overdosage.
The six patients who used imiquimod only occasionally had no erythema and no clinical response. In two patients, the grade of AIN progressed. Four patients failed to comply because of pain from the imiquimod and refusal to refrain from sex. One patient had depression, and one had HIV encephalopathy and so was unable to apply the drug.
Dr. Kreuter's group advises physicians to discuss the need for refraining from sex before patients start therapy. For those unwilling to abstain, or whose illness prevents them from applying the cream, the researchers believe that ablative therapies are the best option.
