Eligibility Details:
Inclusion Criteria:
- 18 years of age or older at screening
- Willing and able to communicate in English
- Willing and able to provide written informed consent to take part in the study;
non-literate individuals may indicate consent with a thumbprint accompanied by the
signature of an objective witness
- Willing and able to provide adequate locator information
- Understand and agree to local Sexually Transmitted Infection (STI) reporting
requirements
- HIV-1 uninfected at screening as documented by Combo Ag/Ab HIV-1/HIV-2 immunoassay
(refer to Appendix II for confirmatory testing algorithm)
- Available to return for all study visits, barring unforeseen circumstances
- Per participant report at screening, a history of consensual Receptive Anal
Intercourse (RAI) at least five times in lifetime
- Per participant report at screening, experience with receiving or self-administering
multiple rectal douches in the context of RAI in the past year.
- If the study participant is currently prescribed oral Tenofovir Disoproxil Fumarate
(TDF) 300 mg/Emtricitabine (FTC) 200 mg (TruvadaTM) as HIV Pre-Exposure Prophylaxis
(PrEP), the participant may continue to take oral TDF/FTC as prescribed as long as the
participant agrees to adhere to a consistent dosing schedule throughout the study
duration.
- If of reproductive potential (defined as pre-menopausal cisgender women or transgender
men who have not had a sterilization procedure per self-report, such as hysterectomy,
bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative beta
human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of ≤ 25
milli-international units per milliliter (mIU/mL)) performed (and results known) on
the same day as and before initiating the protocol-specified study product at Visit 3.
- If of reproductive potential, women must agree to use a reliable form of
contraception, during the trial and for 4 weeks after the final study product doses,
from the list below:
1. Intrauterine device (IUD) or intrauterine system (IUS) that meets <1% failure
rate as stated in the product label.
2. Hormone-based contraceptive that meets <1% failure rate as stated in the product
label
- Willing to abstain from insertion of anything (drug/medication, penis, object, sex
toy, or douche) into the anorectum for 72 hours before and after each research unit
study product exposure and 7 days after each flexible sigmoidoscopy with biopsy
collection.
- Willing to refrain from aspirin and Nonsteroidal anti-inflammatory drug (NSAID) use
for one week before and after each study biopsy visit
- Willing and able to use condoms provided by the study for all RAI for the duration of
participation
- Agrees not to participate in other research studies involving drugs and/ or medical
devices for the duration of the study
Exclusion Criteria:
- History of Hepatitis B infection, as documented by positive HBsAg at screening
- ≥ Grade 2 laboratory abnormality at baseline as defined by Division of AIDS Table for
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 -
July 2017, and Addendum 3 (Rectal Grading Tables for Use in Microbicide Studies)
- Significant colorectal symptom(s) as determined by medical history or by participant
self-report (including but not limited to presence of any unresolved injury,
infectious or inflammatory condition of the local mucosa, history of inflammatory
bowel disease, presence of symptomatic hemorrhoids, and presence of any painful
anorectal conditions that would be tender to manipulation)
- At screening or within the past 2 months: participant-reported symptoms and/or
clinical or laboratory diagnosis of active rectal or reproductive tract infection
requiring treatment per current Centers for Disease Control and Prevention (CDC)
guidelines or symptomatic urinary tract infection (UTI). Infections requiring
treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active Herpes Simplex
Virus (HSV) lesions, chancroid, genital sores or ulcers, and, if clinically indicated,
genital warts. Note that HSV seropositivity with no active genital lesions is not an
exclusion criterion. (Note: if an STI apart from HIV is detected, the participant will
be referred for treatment and can be retested in 30 days and rescreened once.)
- History of an underlying clinically significant cardiac arrhythmia or renal disease
(including creatinine clearance <60 mL/min using Cockcroft-Gault equation)
- Serum phosphate < 2.3 mg/dL
- History of severe or recent cardiac or pulmonary event
- History of significant gastrointestinal bleeding
- Current use of warfarin or heparin or other anticoagulant medications associated with
increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin
[>81 mg], NSAIDs, or Pradaxa®)
- Use of systemic or anorectal immunomodulatory medications within 4 weeks of enrollment
or planned use at any time during study participation
- Per participant report, use of any rectally administered products containing N-9
(including condoms) or investigational products within 4 weeks of enrollment, or
planned use of either at any time during study participation
- Known allergic reaction to TFV or other components of the test articles
- Current known HIV-infected partner(s)
- History of recurrent urticaria
- Symptoms suggestive of acute HIV seroconversion at screening and enrollment
- 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.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
