CROSSOVER STUDY OF ON-DEMAND PREP FORMULATIONS COMPARING RECTAL AND ORAL TENOFOVIR

Exclusion Criteria

• •1. Any reactive/positive HIV test at screening or at least one reactive/positive test result at enrollment, even if HIV infection is not confirmed
• •2. History of active (including chronic) hepatitis B virus (HBV) infection, as documented by positive HBV surface antigen (HBsAg) at screening
• •3. Co-enrollment in any other interventional research study that may interfere with this study (as provided by self-report or other available documentation). Exceptions may be made after consultation with the Clinical Management Committee (CMC).
• •4. ≥ Grade 2 clinically significant laboratory abnormality at baseline as defined by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017, except for estimated glomerular filtration rate (eGFR), which must be \>75 mL/min/1.73m\^2. (Coagulation (PT/INR) results ≥ Grade 2 are not exclusionary for the main study).
• •5. 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 external hemorrhoids, and presence of any painful anorectal conditions that would be tender to manipulation)
• •6. At screening, participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current CDC guidelines or symptomatic urinary tract infection (UTI)
• •a.Infections requiring treatment include chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts.
• •Note: if an STI apart from HIV is detected, the participant will be referred for treatment and, upon documented confirmation of definitive treatment, can be retested in three weeks for evidence of adequate treatment.
• •7. History of an underlying clinically significant cardiac arrhythmia or renal disease
• •8. History of severe or recent cardiac or pulmonary event
• •9. History of significant gastrointestinal bleeding
• •10. Use of F/TDF or use of F/TAF as HIV PrEP within 8 weeks prior to screening visit or anticipated use throughout study participation
• •11. Use of injectable PrEP within 8 weeks prior to the screening visit or anticipated use throughout study participation
• •12. Use of systemic or anorectal immunomodulatory medications, rectally administered products containing N-9 or corticosteroids, or any investigational products unless otherwise permitted within 4 weeks of screening or planned use at any time during study participation
• •13. Known allergic reaction to TFV or other components of the test articles
• •14. Current known partners with HIV, unless with sustained viral suppression on antiretroviral treatment (ART)
• •15. History of recurrent urticaria
• •16. Symptoms suggestive of acute HIV infection at screening or enrollment
• •17. 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
• •ADDITIONAL EXCLUSION FOR THOSE IN THE PK/PD SUB-STUDY
• •1. Current medically-indicated use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin \[\>81 mg\], non-steroidal anti-inflammatory drugs \[NSAIDs\], or Pradaxa®)
• •2. Previous use of injectable PrEP
• •3. ≥ Grade 2 laboratory result for coagulation testing (PT/INR) at baseline as defined by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.