Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions

Inclusion Criteria:

• HIV-positive; documentation of HIV infection must be based on a federally approved,licensed HIV test performed in conjunction with screening (enzyme linkedimmunosorbent assay [ELISA], western blot, or other test); alternatively, thisdocumentation may include a record that another physician has documented that thepatient has HIV based on prior ELISA and western blot; an approved antibody testwill be used to confirm diagnosis; if the physician is treating a patient withcombination antiretroviral therapy (cART) with a history of HIV positivity based onan approved antibody test then repeat antibody confirmation is not necessary

• Biopsy-proven HSIL (anal intraepithelial neoplasia 2 (AIN2) and/or AIN3) of the analcanal at either the squamocolumnar junction or distal anus, documented within 60days prior to enrollment, but not less than 1 week prior to enrollment

• HSIL occupies at least 25% of the circumference of the anal canal at either thesquamocolumnar junction or distal anus on high-resolution anoscopy (HRA) atscreening or entry based on available biopsy results and visual appearance

• Anal HSIL lesions are visible at study entry and no lesions are suspicious forinvasive cancer

• Ability to understand and willing to provide informed consent

• Participants must, in the opinion of the Investigator, be capable of complying withthe requirements of this protocol including self-administration of study treatment

• Karnofsky performance status of >= 70%

• Cluster of differentiation (CD)4 count >= 200 within 120 days prior to enrollment orplasma HIV-1 ribonucleic acid (RNA) < 200 copies/mL within 120 days prior toenrollment

• For females, cervical cytology (if having a cervix) and gynecologic evaluationwithin 12 months prior to enrollment

• Absolute neutrophil count (ANC) > 750 cells/mm^3 within 90 days prior to enrollment

• Hemoglobin >= 9.0 g/dL within 90 days prior to enrollment

• Platelet count >= 75,000/mm^3 within 90 days prior to enrollment

Exclusion Criteria:

• History of anal cancer

• Prior intra-anal use of topical 5-fluorouracil 5% or imiquimod 2.5%, 3.75% or 5% atany point, or use of perianal imiquimod 2.5%, 3.75% or 5% or topical 5-fluorouracil 5% within 6 months prior to enrollment

• Extensive concurrent perianal or lower vulvar HSIL or condyloma requiring adifferent treatment modality than the study treatment, or treatment that cannot bedeferred in observation arm, per examining provider

• Condyloma occupying more than 50% of the circumference of the anal canal or thatobscures a satisfactory exam

• Ongoing use of anticoagulant therapy other than aspirin or nonsteroidalanti-inflammatory drugs (NSAIDs)

• Acute treatment for an infection (excluding fungal infection of the skin andsexually transmitted infections) or other serious medical illness within 14 daysprior to study entry

• Malignancy requiring systemic therapy; note: Kaposi's sarcoma limited to the skin isnot exclusionary unless requiring systemic chemotherapy

• Concurrent systemic corticosteroids, cytokines, and immunomodulatory therapy (e.g.interferons)

• Prior history of HPV vaccination

• Treatment for anal or perianal HSIL, low-grade squamous intraepithelial lesion (LSIL) or condyloma within 4 months of entry; please note that infrared coagulation (IRC) or electrocautery of a biopsy site to stop bleeding does not constitutetreatment

• Female participants who are pregnant or breastfeeding; women of childbearingpotential must have a negative urine or serum pregnancy test within 72 hours priorto initiating study treatment; all women of childbearing potential must be willingto comply with an acceptable birth control regimen to prevent pregnancy whilereceiving treatment and for 3 months after treatment is discontinued as determinedby the Investigator; post-menopausal women must be amenorrheic for at least 12months to be considered of non-childbearing potential; (note: a woman ofchildbearing potential is one who is biologically capable of becoming pregnant; thisincludes women who are using contraceptives or whose sexual partners are eithersterile or using contraceptives)