Rectal Microbicide Safety and Acceptability Trial of Topically Applied Tenofovir Compared With Oral Tablet

Inclusion criteria

• ≥ Age of 18 at screening
• Willing and able to provide written informed consent for screening and enrollment
• HIV-1 uninfected at screening according to the standard DAIDS algorithm in Appendix II
• Willing and able to communicate in English
• Willing and able to provide adequate locator information, as defined in site standard operating procedures (SOP)
• Availability to return for all study visits, barring unforeseen circumstances
• Per participant report at screening, a history of consensual RAI at least once in the prior year
• Willing to abstain from insertion of anything rectally including sex toys, other than the study gel during the active phases of the study and for 5 days following biopsy collection
• Willing to abstain from sexual intercourse (rectal and vaginal) during the active phases of the study and for 5 days following biopsy collection
• Must agree to use study provided condoms for the duration of the study for vaginal and insertive anal intercourse
• Must be in general good health
• Must agree not to participate in other drug trials

In addition to the criteria listed above, female participants must meet the following criteria:

• Post-menopausal or using (or willing to use) an acceptable form of contraception (e.g., barrier method, IUD, hormonal contraception, surgical sterilization, or vasectomization of male partner). If the female participant has female partners only, the method of contraception will be noted as a barrier method in the study documentation.

Exclusion criteria

• 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 of the local mucosa, and presence of symptomatic external hemorrhoids)
• At screening, clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines or urinary tract infection (UTI). Infections requiring treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or symptomatic genital warts requiring treatment. Note that HSV-2 seropositive with no active lesions is allowed, since treatment is not required.

Note: Allow one re-screening after documented treatment (30 days) in cases of GC/CT identified at screening

• At screening:

• Positive for hepatitis B surface antigen
• Hemoglobin < 10.0 g/dL
• Platelet count < 100,000/mm3
• White blood cell count less than 2,000 cells/mm3 or > than 15,000 cells/mm3
• Calculated creatinine clearance less than 80 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 females)/72 x (serum creatinine in mg/dL)
• Serum creatinine > 1.3× the site laboratory upper limit of normal (ULN)
• ALT and/or AST > 2.5× the site laboratory ULN
• +1 glucose or +1 protein on urinalysis (UA)
• History of bleeding problems (i.e. INR > 1.5× the site laboratory ULN or PTT > 1.25× the site laboratory ULN)
• History of significant gastrointestinal bleeding in the opinion of the investigator
• Allergy to methylparaben, propylparaben, sorbic acid
• 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
• 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
• NSAIDS
• Acyclovir
• Valacyclovir
• TDF
• Any other drugs that are associated with increased likelihood of bleeding following mucosal biopsy
• By participant report at screening, use of 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
• History of recurrent urticaria
• 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:

• Pregnant at Enrollment/Baseline Evaluation Visit
• Breastfeeding or intent to breastfeed during duration of study