CHIPP-PrEP: Cabotegravir-Hormone Interrogation of Pharmacokinetics/Pharmacodynamics (PK/PD) for HIV Prevention

The CHIPP-PrEP protocol is a phase 1, open label study to compare the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of long-acting cabotegravir injectable (CAB-LA) administration in adults aged 19 years or older. Long-acting cabotegravir (Apretude™) is an FDA-approved injectable antiretroviral medication administered every two months for HIV pre-exposure prophylaxis (PrEP). While clinical efficacy trials have demonstrated CAB-LA's effectiveness in preventing HIV infection, knowledge gaps remain regarding drug penetration into mucosal tissues where HIV transmission primarily occurs and potential drug-drug interactions with therapeutic hormone therapies. Current PK data derives predominantly from plasma measurements, which may not accurately reflect drug concentrations at actual sites of HIV exposure in rectal and genital mucosa. This study addresses these critical gaps by directly measuring CAB-LA concentrations in blood, mucosal tissues, and genital secretions across three distinct population cohorts: males not using exogenous hormones, males using therapeutic hormone therapy, and females using non-hormonal contraception. This design enables isolation of hormone effects on CAB-LA pharmacokinetics while controlling for biological sex differences.

Following successful screening, eligible participants will return for a Baseline Visit (Day 0) to complete pre-treatment evaluations. At baseline, participants will undergo laboratory assessment of circulating hormone concentrations (estradiol and testosterone), HIV antibody/antigen and RNA testing to confirm HIV-negative status, and collection of rectal biopsies (all participants) and cervical biopsies (females only) for baseline HIV explant challenge pharmacodynamic assessment. These baseline tissue samples undergo ex vivo HIV-1 challenge experiments to establish pre-treatment viral susceptibility prior to CAB-LA exposure. One week following baseline biopsy collection (Visit 1, Day 7), participants will be administered a single 3 mL intramuscular injection of 600 mg cabotegravir long-acting injectable suspension (Apretude™, ViiV Healthcare; 200 mg/mL formulation) using the recommended ventrogluteal approach by licensed clinical staff.

Biopsy Collection Visits will occur at study visits 2,4, 6, 7, and 8 (Days 7, 14, 35, 63, and 91). At these intensive study visits, blood will be collected for hormone testing (estradiol and testosterone), plasma CAB-LA concentration determination, and eGFR monitoring. Rectal fluid and cervicovaginal fluid will be collected using specialized swabs to measure mucosal drug concentrations. Rectal biopsies (all participants) and cervical biopsies (females only) will be collected using flexible sigmoidoscopy and standard gynecological techniques, respectively, for both tissue drug concentration measurement and pharmacodynamic HIV explant challenge experiments.

Interim Pharmacokinetic Visits (Visits 3 and 5 at Days 10 and 21): Blood will be collected for plasma CAB-LA concentration determination, eGFR assessment, and hormone measurements. A final safety visit (Visit 9 at Day 98) will be performed. Select concomitant medications, with particular emphasis on exogenous hormones and medications that may affect cabotegravir or hormone metabolism, will be collected on daily concomitant medication logs maintained by participants throughout the study.

Safety assessments, including history/physical, chemistry/hematology labs at screening and interim history will be performed at study visits