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A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod

Fox, Paul Aa; Nathan, Mayurab; Francis, Nicholasc; Singh, Naveenad; Weir, Justinc; Dixon, Glenc; Barton, Simon Ea; Bower, Marka

doi: 10.1097/QAD.0b013e32833d466c
Clinical Science

Objective: To determine whether imiquimod was more effective than placebo for the treatment of high-grade anal canal intraepithelial neoplasia (HG-ACIN).

Design: Double-blind, randomized placebo-controlled clinical trial.

Methods: Sixty-four HIV-positive patients were randomized to self-application of imiquimod cream or matched placebo into the anal canal three times a week for 4 months. Response was assessed by cytology, high-resolution anoscopy and biopsy 2 months after therapy. All patients who failed to resolve were offered treatment with open-label imiquimod for a further 4 months.

Results: Fifty-three patients completed the study, of which 28 patients were on active drug and 25 patients on placebo. In the imiquimod group, four patients resolved and eight patients downgraded to low-grade squamous intraepithelial lesion (LSIL) with a median follow-up of 33 months. In the placebo group, one patient resolved. Imiquimod was significantly associated with a positive outcome (P = 0.003). Only one patient discontinued owing to side effects. Twenty-one patients entered a second open-label phase of treatment. Five of these patients cleared their anal canal intraepithelial neoplasia (ACIN) and four patients downgraded to LSIL. The overall mean duration of follow-up was 36 months. During this extended follow-up period, 61% have exhibited sustained absence of high-grade squamous intraepithelial lesion (HSIL).

Conclusion: This study demonstrates the effectiveness of imiquimod for the treatment of ACIN, and the benefit of prolonged or repeated treatments. This form of therapy is likely to be especially valuable for patients with widespread multifocal ACIN who are otherwise difficult to treat, and should be considered as an adjunct to ablative therapy.

aChelsea and Westminster Hospital NHS Trust, UK

bHomerton Hospital NHS Trust, UK

cDepartment of Cellular Pathology, Imperial College Healthcare NHS Trust, UK

dDepartment of Pathology, Barts and the London NHS Trust, London, UK.

Received 22 April, 2010

Revised 16 June, 2010

Accepted 16 June, 2010

Correspondence to Paul A. Fox, Chelsea and Westminster Hospital NHS Trust, 369 Fulham Road, London, SW10 9NH, UK. E-mail:

© 2010 Lippincott Williams & Wilkins, Inc.