Cabotegravir-Hormone PK/PD Interactions for HIV Prevention

Inclusion criteria

• 19 years of age or older
• For persons using exogenous hormones, must be on a stable regimen for ≥6 months and remain on that regimen throughout study conduct, and exogenous hormone regimens must be prescribed and managed under the care of a healthcare professional
• For females, must be on a non-hormonal contraceptive agent, and must persist in contraceptive use for the duration of the study
• Body weight greater than 35 kg (77.2 lbs)
• HIV-1 uninfected at screening and enrollment as documented by an instrumented Ag/Ab assay and HIV-1 RNA testing
• Understand and agree to local STI reporting requirements
• Willing to abstain from additional antiretroviral agents (including PrEP agents, F/TAF and F/TDF) during the duration of the study
• Willing to abstain from insertion of anything (drug, enema, penis, or sex toy) in the rectum or vagina for 72 hours before and 72 hours after each flexible sigmoidoscopy
• Willing to refrain from aspirin and NSAID use for one week before and after each study biopsy visit
• Willing and able to use condoms for all receptive anal intercourse and receptive vaginal intercourse for the duration of study participation
• Able and willing to communicate in English
• Able and willing to provide written informed consent to take part in the study
• Able and willing to provide adequate information for locator purposes
• Availability to return for all study visits, barring unforeseen circumstances
• Agree not to participate in other research studies involving drugs and/or medical devices for the duration of the study

Exclusion criteria

• History of previous long-acting antiretroviral use, including CAB-LA and long-acting lenacapavir
• History of oral PrEP (F/TDF, F/TAF) use within the prior eight weeks
• For females, if a participant is pregnant or plans to become pregnant during study duration
• For females, if the participant is actively breastfeeding
• For females, if the participant is post-menopausal or accessing exogenous hormone replacement therapy
• For females, has irregular menstrual cycles
• Has a tattoo or other dermatological condition which may interfere with product administration or interpretation of injection site reactions
• Surgically-placed or injected buttock implants or filler, per self-report
• One or more reactive or positive HIV test results at screening or enrollment, even if HIV infection is not confirmed
• Current known HIV-infected partner(s)
• Symptoms suggestive of acute HIV seroconversion at screening and enrollment
• Known or suspected allergy to CAB-LA
• Any ≥ 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 rectal 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 genital infection requiring treatment per current CDC guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts. 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 re-screened once.)
• History of significant gastrointestinal bleeding
• Clinically significant cardiovascular disease, as defined by history of symptomatic arrhythmia, ischemia, or other significant cardiac disease
• 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 or vaginally 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
• 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.
• Individuals with neocervix will be excluded from giving cervical biopsies, if eligible for study participation.