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Tuesday, March 6, 2012

Long-acting, intramuscular formulation of ripilvirine for PrEP

PRN Report from 19th CROI:

Noting adherence problems seen in several studies of daily oral PrEP, Akil Jackson, from the St Stephen’s AIDS Trust in London, presented data on a long-acting formulation of rilpivirine for intramuscular injection. Rilpivirine Long-Acting (RPV-LA) is a parenteral formulation containing 300 mg/mL, allowing prolonged plasma exposure and potentially monthly or less frequent dosing. This study explored the pharmacokinetics in plasma, the female genital tract and male rectum over 84 days after a single intramuscular dose.This prospective, open-label stratified-dose exploratory study investigated plasma and body fluid/tissue pharmacokinetics in healthy volunteers with low behavioral risk for HIV. Volunteers aged 18 to 50 were screened for general health, HIV and sexually transmitted infections.

Twenty-seven female participants received a single intramuscular dose (gluteus maximus) at 300, 600, or 1200 mg with plasma for RPV levels collected on days 0 (pre-dose and 4 and 8 hours), 1, 3, 7, 11, 14, 21, 28, 42, 56, and 84. Female genital tract fluid was sampled from the posterior fornix at a similar times from 8 hours onward, using a volumetric aspiration device. Biopsies of vaginal epithelium from the peri-cervical fornices were taken at days 14 and (7 or 28) for tissue pharmacokinetics.

A small sub-study with 6 male subjects received an intramuscular dose of 600 mg, with plasma pharmacokinetics (a similar schedule) and rectal biopsies at days 7 and 14. Male rectal fluid was collected with an ophthalmic spear/sponges administered though a proctoscope; fecal contamination may have had a dilutional effect.

All doses were well tolerated; no serious adverse event and no prolongation of QT interval on ECG. Each of the 3 RPV-LA doses in female subjects exhibited prolonged plasma and genital tract exposure supporting further exploration as potential PrEP agent. Rectal secretion concentrations in male subjects were low, most likely due to dilutional effect of fecal contamination, but reassuringly, the male rectal tissue concentrations were equivalent to those in plasma.

Dr Jackson noted that the safety, pharmacokinetics and pharmacodynamics after multiple IM RPV-LA doses will be important further information for future development.

Jackson A, Else L, Tjia J, Seymour N, Stafford M, Back D, Gazzard B, Boffito M. Rilpivirine-LA Formulation: Pharmacokinetics in Plasma, Genital Tract in HIV– Females and Rectum in Males. Presented March 6, 2012 at the 19th CROI, Seattle, WA. Oral Abstract #35.

Source: Source: Reporting from Seattle for PRN News: James Braun DO