The Journal of antimicrobial chemotherapy · 2026
Inter- and intraindividual variability of long-acting injectable cabotegravir/rilpivirine trough concentrations after 1 year of continuous use.
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Sunagawa Shawnalyn W, Havens Joshua P, Bares Sara H, Kubat Maureen, O'Neill Jennifer, Lyden Elizabeth, Mykris Timothy, Winchester Lee C, Weinhold Jonathan, Avedissian Sean N, Podany Anthony T, Fletcher Courtney V, Scarsi Kimberly K
Аннотация
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.
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.