Inter- and intraindividual variability of long-acting injectable cabotegravir/rilpivirine trough concentrations after 1 year of continuous use.

OBJECTIVES: Long-acting injectable (LAI) cabotegravir/rilpivirine demonstrates substantial inter- and intraindividual variability in trough concentrations during the first year of use. We aimed to characterize trough concentration variability of cabotegravir and rilpivirine after >12 months of continuous use. METHODS: We conducted a prospective pharmacokinetic study in virologically suppressed people with HIV receiving bimonthly LAI cabotegravir/rilpivirine 600 mg/900 mg. Plasma trough samples were collected prior to three consecutive doses over 6 months for drug quantitation. Primary outcomes were inter- and intraindividual variability defined as coefficient of variation (CV) and intraclass correlation coefficient (ICC). Secondary outcomes included concentrations below the proposed 4x-protein-adjusted 90% inhibitory concentration (PA-IC90) for cabotegravir (4x-PA-IC90 = 664 ng/mL) and rilpivirine (4x-PA-IC90 = 48 ng/mL). RESULTS: Among 50 participants, 150 samples were collected. Participants were primarily male (80%) with a median age of 45 years and a body mass index of 28 kg/m2. Median interindividual CVs were high for both cabotegravir [58%, interquartile range (IQR): 15, 59] and rilpivirine (52%, IQR: 18, 59). Median intraindividual CVs were moderate for both cabotegravir (24%, IQR: 15, 39) and rilpivirine (23%, IQR: 15, 39), with ICCs indicating good intraindividual agreement for cabotegravir (0.82) and moderate intraindividual agreement for rilpivirine (0.72). Twelve (8%) cabotegravir concentrations in 8 participants and 24 (16%) rilpivirine concentrations in 16 participants were below 4x-PA-IC90; however, all participants maintained virologic suppression throughout the study period. CONCLUSIONS: After one year of continuous use, inter- and intraindividual variability persists for cabotegravir and rilpivirine, indicating that clinical decisions should not be based on only one trough concentration.