Pharmacokinetics of a Long-Acting Monthly Injection of Rilpivirine in Patients With HIV Infection

Researchers conducted a study to assess the pharmacokinetics of a long-acting formulation of rilpivirine for the treatment of patients with HIV infection.

Results of a population study found that a long-acting (LA) formulation of rilpivirine administered monthly for the treatment of patients with HIV infection was absent of a clinically relevant effect of covariates on rilpivirine pharmacokinetics. These findings were published in the Journal of Antimicrobial Chemotherapy.

This analysis was conducted using pooled data from 4 phase 1 studies, 1 phase 2b study, and 2 phase 3 studies. Healthy volunteers (n=131) and patients with HIV infection (n=855) were given 300 to 1200 mg of rilpivirine as a single dose or in multiple doses every 4 or 8 weeks. The phase 3 studies used a treatment regimen comprising an oral lead-in period of rilpivirine 25 mg once daily for 4 weeks, followed by an intramuscular (IM) injection of a 900-mg dose of LA rilpivirine, and subsequent monthly IM injections with a 600-mg dose of LA rilpivirine. Rich and sparse rilpivirine plasma concentrations were assessed.

Compared with the phase 3 studies, rilpivirine exposure was increased by 41.3% and 17.5% in the phase 1 and 2b studies, respectively. The researchers found that concentrations of rilpivirine had a 1.14-fold increase during the oral lead-in period.

Rilpivirine was found to be absorbed in a 1-compartment model with 2 parallel, sequential, zero-first-order pathways comprising slow and fast absorptions with a linear elimination. The half-life of the LA rilpivirine formulation was observed to be 200 days.

Age was found to be a statistically significant covariate of the fast absorption pathway (minimum value of objective function, -18.8; P <.001), in which the fast absorption was decreased with increasing age. Patients who were twice the age of younger patients included in the analysis had a 45% decreased maximum concentration of plasma rilpivirine.

After adjustment for the effect of patient age on the fast absorption pathway, no other covariates including body weight, BMI, sex, ethnicity, health status, or needle length were found to be statistically significant. Rilpivirine concentrations were highly consistent between patient subgroups, and no clinically relevant variations were reported.

This study was limited by its small sample size and its inclusion of only 6 men.

These data indicated that a 1-compartment, parallel absorption pathway best fit the pharmacokinetic process of rilpivirine. These findings “suggest that dose adjustments [for LA rilpivirine] are not warranted for specific [patient] subgroups,” the researchers concluded.

Disclosure: Some author(s) declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Neyens M, Crauwels HM, Perez-Ruixo JJ, Rossenu S. Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV. J Antimicrob Chemother. 2021;dkab338. doi:10.1093/jac/dkab338