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A Pilot Study of the Immunologic, Virologic, and Pathologic Consequences of Intra-anal 5% Imiquimod in HIV-1–Infected Men With High-Grade Squamous Intraepithelial Lesions

Cranston, Ross, D., M.D., F.R.C.P.1; Baker, Jonathan, R., P.A.-C.2; Siegel, Aaron, B.A.3; Brand, Rhonda, M., Ph.D.3–5; Janocko, Laura, Ph.D.3; McGowan, Ian, M.D., Ph.D., F.R.C.P.3,4

Diseases of the Colon & Rectum: March 2018 - Volume 61 - Issue 3 - p 298–305
doi: 10.1097/DCR.0000000000000991
Original Contributions: Anal Neoplasia
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BACKGROUND: Imiquimod can be used to treat internal anal high-grade squamous intraepithelial lesions. In HIV-1–infected individuals there is a theoretical concern for increased HIV replication in anorectal tissue secondary to imiquimod-induced mucosal inflammation.

OBJECTIVE: The purpose of this study was to assess local virologic, immunologic, and pathologic effects of imiquimod treatment in HIV-infected individuals.

DESIGN: This was a pilot study at a single academic center.

SETTINGS: The study was conducted at the University of Pittsburgh Anal Dysplasia Clinic.

PATIENTS: HIV-1–infected individuals with biopsy-confirmed internal anal high-grade squamous intraepithelial lesions were included.

INTERVENTION: Imiquimod cream was prescribed for intra-anal use 3 times per week for 9 weeks.

MAIN OUTCOME MEASURES: Anal human papillomavirus typing, anal and rectal tissue HIV-1 RNA and DNA quantification, cytokine gene expression, and anal histology were measured.

RESULTS: Nine evaluable participants (1 participant was lost to follow-up) were all white men with a median age of 46 years (interquartile range = 12 y) and a median CD4 T-cell count of 480 cells per cubic millimeter (interquartile range = 835). All were taking antiretroviral therapy, and 7 of 9 had HIV-1 RNA <50 copies per milliliter. The median dose of imiquimod used was 27.0 (interquartile range = 3.5), and there was a median of 11 days (interquartile range = 10 d) from last dose to assessment. There was no progression to cancer, no significant change in the number of human papillomavirus types detected, and no significant change in quantifiable cytokines/HIV-1 RNA or DNA levels in anal or rectal tissue. Seven (35%) of 20 high-grade lesions resolved to low-grade squamous intraepithelial lesions.

LIMITATIONS: The study was limited by the small number of participants and variable time to final assessment.

CONCLUSIONS: Intra-anal imiquimod showed no evidence of immune activation or increase in HIV-1 viral replication in anal and rectal tissue and confirmed efficacy for intra-anal high-grade squamous intraepithelial lesion treatment morbidity. See Video Abstract at http://links.lww.com/DCR/A498.

1 Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

2 University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

3 Magee–Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania

4 Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

5 Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania

Funding/Support: This work was supported by a supplement from the National Cancer Institute (5P30CA047904-26).

Financial Disclosure: Dr Cranston receives royalties from UpToDate medical encyclopedia and Dr McGowan is a Novicol Life Sciences board member and a consultant for ABIVAX and Aelix Therapeutics.

Presented at the 29th International Union Against Sexually Transmitted Infections European Conference on Sexually Transmitted Infections, Sitges, Spain, September 24 to 26, 2015.

Correspondence: Ross D. Cranston, M.D., F.R.C.P., Fundació Lluita contra la Sida, Hopsital Universitari Germans Trias i Pujol, Badalona 08916, Spain. E-mail: rdcranston@outlook.com

© 2018 The American Society of Colon and Rectal Surgeons