Real-life therapeutic concentration monitoring of long-acting cabotegravir and rilpivirine: Preliminary results of an ongoing prospective observational study in Switzerland.  Pharmaceutics
Thoueille et al. assessed cabotegravir (CAB) and rilpivirine (RPV) plasma concentrations in a preliminary analysis of individuals who receive long-acting CAB/RPV within the Swiss HIV Cohort Study.
Plasma drug concentrations were measured among individuals who received CAB/RPV either as oral lead-in or as intramuscular injection (at 4- or 8-week intervals) at unselected time-points using high-performance chromatography coupled to tandem mass spectrometry (LC-MS/MS).
Within five months after the approval of CAB/RPV in Switzerland, 46 individuals who received CAB/RPV were included in the present analysis. Study participants were predominantly male (83%) and Caucasian (63%), with 61% being less than 50 years old. Overall, 54% had a BMI above 25 kg/m2, and seven (15%) were considered to be obese. Intramuscular injections were administered without oral lead-in in 8 (17%) individuals, and 96% received injections every 8 weeks. Although observed drug concentrations were generally within the ranges reported in registration trials, the authors observed a considerable inter-individual variability of drug levels for both CAB and RPV and unexpectedly low RPV concentrations which were only two-times above the 90% inhibitory concentration (IC90). Viral blips were observed in 3 individuals overall within the study period, but no viral failures occurred.
In summary, the present study highlights the importance of monitoring CAB/RPV drug levels in a real-life cohort outside of randomized registration trials. The considerable inter-individual variability and the low RPV concentrations observed warrant further investigation. Population pharmacokinetic models may provide valuable tools to evaluate individual factors affecting drug levels and to optimize long-acting ART for our patients.