Rilpivirine long-acting (RPV-LA) is a parenteral formulation, allowing prolonged plasma exposure. We explored its multiple compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis (PrEP).Sixty-six HIV-negative volunteers were enrolled; females received an intramuscular dose of 300, 600, or 1200 mg with plasma and genital levels measured to 84 days post-dose. Males receiving 600 mg had similar PK determined in plasma and rectum. Ex-vivo antiviral activity of cervico-vaginal lavage (CVL) was also assessed.After single dose, RPV concentrations peaked at day 6-8 and were present in plasma and GT fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma.With the 1200mg dose, CVL showed greater antiviral activity, above baseline, at days 28 & 56. All doses were well tolerated.All doses gave prolonged plasma and genital tract rilpivirine exposure. PK and viral inhibition of repeated RPV-LA doses will be important in further dose selection.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 26 May 2014 doi:10.1038/clpt.2014.118.
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