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.

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.