Rectal Microbicide Acceptability, Tolerability and Adherence

Inclusion Criteria: 1. Men (cis or transgender) and TGW who are 18-35 years old at Screening, verified per site SOP. 2. Able and willing to provide written informed consent. 3. HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results. 4. Able and willing to provide adequate locator information, as defined in site SOP. 5. Available to return for all study visits and willing to comply with study participation requirements. 6. In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee. 7. At Screening, history of consensual RAI at least three times in the past three months and expecting to maintain at least this frequency of RAI during study participation per participant report. 8. Willing to not take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation (including the time between Screening and Enrollment). 9. For individuals who can get pregnant (i.e., TGM with a female reproductive system): a negative pregnancy test at Screening and Enrollment. 10. For individuals who can get pregnant: Per participant report at Enrollment, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment and intending to use an effective method for the duration of study participation; effective methods include: 1. Hormonal methods; 2. Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions); 3. Sterilization (of participant or, if in a monogamous relationship, of partner, as defined in site SOPs); 4. Abstinence from RVI for 90 days prior to Enrollment, and intention to abstain from RVI for the duration of study participation. Exclusion Criteria: 1. At Screening: 1. History of inflammatory bowel disease; 2. Current anorectal condition that would impede product placement or assessment of tolerability by participant report or exam. 2. Anticipated use and/or unwillingness to abstain from using non-study rectally-administered medications and products during study participation, including personal lubricants containing nonoxynol-9 (N-9). Note: The use of non-study personal lubricants and usual pre-RAI douches that do not contain N-9 is permitted during study participation. 3. Known adverse reaction to any of the components of the study products. 4. Participation in research studies involving drugs, medical devices, genital products, or vaccines within 30 days of the Enrollment Visit. 5. Participation in research studies involving rectal products (ever). 6. Per participant report, use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment. 7. In the 3 months prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is HIVpositive and either not on ART or of unknown ART use status (by self report). 8. In the month prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is of unknown HIV status and unknown PrEP/ART use status (by self-report). 9. Non-therapeutic injection drug use in the 12 months prior to Enrollment. 10. At either Screening or Enrollment, participant-reported symptoms and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection (RTI) requiring treatment per current WHO guidelines (http://www.who.int/hiv/ pub/sti/pub6/en/), or symptomatic urinary tract infection (UTI). Infections requiring treatment include: Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts, chancroid, pelvic inflammatory disease (PID), symptomatic bacterial vaginosis (BV), symptomatic vaginal candidiasis, and trichomoniasis. Note: Otherwise eligible participants with a symptomatic UTI or an STI/RTI requiring treatment per current WHO guidelines may be retested during the screening process and if treatment is completed and symptoms have resolved within the screening window the participant may be enrolled. Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is permitted since treatment is not required. 11. For individuals who can get pregnant: Pregnant or breastfeeding at either Screening or Enrollment or planning to become pregnant during study participation. 12. For individuals who can get pregnant: Last pregnancy outcome 90 days or less prior to Screening. 13. Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.