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.
Author(s): Fox PA, Nathan M, Francis N, Singh N, Weir J, Dixon G, Barton SE, Bower M.
Affiliation(s): Chelsea and Westminster Hospital NHS Trust, London, UK. paul.fox@chelwest.nhs.uk
Publication date & source: 2010, AIDS. , 24(15):2331-5
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.
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