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


METHODS
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).


CONCLUSIONS
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.
Fox
Paul A
PA
Chelsea and Westminster Hospital NHS Trust, London, UK. paul.fox@chelwest.nhs.uk
Nathan
Mayura
M
Francis
Nicholas
N
Singh
Naveena
N
Weir
Justin
J
Dixon
Glen
G
Barton
Simon E
SE
Bower
Mark
M
D000279:Administration, Cutaneous; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1 / Q000187:drug effects*; D018451:Homosexuality, Male; D006801:Humans; D000077271:Imiquimod; D008297:Male
D000634:Aminoquinolines; D000077271:Imiquimod