Rectal Safety and Acceptability Study of Tenofovir 1% Gel

Exclusion Criteria

• •1. Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition
• •2. At screening: participant-reported symptoms, and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current Centers for Disease Control (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or symptomatic genital warts requiring treatment. Note that an HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required Note: In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after screening visit will be allowed
• •3. Anorectal sexually transmitted infections (STI) within six months prior to the Screening Visit
• •4. At screening:
• •Positive for hepatitis B surface antigen Hemoglobin \< 10.0 g/dL Platelet count less than 100,000/mm3 White blood cell count \< 2,000 cells/mm3 or \> 15,000 cells/mm3 For females: calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min (140- age in years) x (weight in kg) x (0.85 for female)/72 x (serum creatinine in mg/dL) For males: calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL) Serum creatinine \> 1.3× the site laboratory upper limit of normal (ULN) Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \> 2.5× the site laboratory ULN
• •+1 glucose or +1 protein on urinalysis (UA) History of bleeding problems
• •5. History of significant gastrointestinal bleeding in the opinion of the investigator
• •6. Allergy to methylparaben, propylparaben, sorbic acid, and components of N-9
• •7. Known HIV-infected partners
• •8. By participant report at enrollment, history of excessive daily alcohol use (as defined by the CDC as heavy drinking consisting of an average consumption of more than 2 drinks per day for men, and more than 1 drink per day for women), frequent binge drinking or illicit drug use that includes any injection drugs, methamphetamines (crystal meth), heroin, or cocaine including crack cocaine, within the past 12 months
• •9. Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation: Heparin, including Lovenox® Warfarin Plavix® (clopidogrel bisulfate) Rectally administered medications (including over-the-counter products) Aspirin Non-steroidal anti-inflammatory drugs (NSAIDS) Any other drugs that are associated with increased likelihood of bleeding following mucosal biopsy
• •10. By participant report at screening, use of post-exposure prophylaxis for HIV exposure, systemic immunomodulatory medications, rectally administered medications, rectally administered products (including condoms) containing N-9, or any investigational products within the 4 weeks prior to the Enrollment/Baseline Evaluation Visit and throughout study participation
• •11. History of recurrent urticaria
• •12. Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease In addition to the criteria listed above, female participants will be excluded if they meet any of the following criteria:
• •13. Pregnant at the Enrollment/Baseline Visit
• •14. Breastfeeding at screening or intend to breastfeed during study participation per participant report.