Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long‐acting formulation in healthy volunteers

Abstract

Single and multiple i.m. injections of RPV LA demonstrated favourable local/systemic tolerability in healthy volunteers. RPV pharmacokinetics suggested that clinically relevant plasma concentrations can be achieved with this LA formulation.

Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

“…Although untreated macaques were not included as a comparison control, the peaks and set points of plasma viremia in the two animals in this study were similar to those in our previous study (30). While RPV LA dosing of and metabolism in macaques were different than those in humans, its administration in this study led to plasma RPV concentrations detected in the animals that were comparable to concentrations reported for humans who received 600-mg RPV LA doses (22,24). RPV LA treatment displayed a therapeutic effect with approximate 2-log decreases in plasma (12) N54S (1) D76G (1) E79G (1) G112D (1) G155R (1 viremia 1 week after treatment that was sustained for roughly 15 weeks after the first injection, and viremia increased as plasma RPV concentrations dropped below 25 ng/ml (68 nM).…”

“…During these trials, patients failing RPV-based ART also tended to select unique NNRTI-associated resistance mutations in reverse transcriptase (RT) compared with those on an efavirenz-based regimen (20). Long-acting rilpivirine (RPV LA) is an injectable nanoparticle formulation and has been shown to be safe and tolerable, with detectable drug concentrations maintained in plasma and tissues weeks after a single injection (21)(22)(23)(24). Multiple clinical trials are under way to test safety and acceptability of RPV LA as PrEP in HIV-1-uninfected men and women (13).…”

Formulation and pharmacology of long-acting rilpivirine

“…A small Phase I clinical study investigated the safety, tolerability and pharmacokinetics of RPV LA (G001, 300 mg/ml) in HIV-seronegative participants [22]. Three separate cohorts of individuals received either 300 mg (1 ml) single dose, 600 mg (2 ml) single dose or 1,200 mg (2 Â 2 ml) single dose, followed, in this third cohort only, by two 600 mg doses at 4-week intervals.…”

Durability of Boosted Atazanavir (ATV) or Darunavir (DRV) Plus Maraviroc (MVC) Dual rescue Therapy in Poorly Adherent Subjects in View of Long-Acting Drugs

“…Nanoformulation allows drugs to maintain stable plasma levels over time [5,6], overcoming the problem of daily adherence but not that of adherence to a monthly schedule. This paper presents an update of the preliminary data published elsewhere [7], concerning the concept of a 'disposable' regimen, in which the high risk of drug failure may not hamper the future eligibility of patients for long-acting regimens.…”