Rapid achievement of protective cabotegravir concentrations in a real-world HIV PrEP cohort

To assess early cabotegravir (CAB) long-acting (LA) plasma concentrations following initiation of HIV pre-exposure prophylaxis (PrEP).

This was a prospective pharmacokinetic study of individuals initiating CAB-LA PrEP, administered as 600 mg intramuscular injections into the gluteal muscle (two initial doses 28 days apart, followed by injections every 56 days). Plasma samples for therapeutic drug monitoring were collected on days 3, 7, 28, and 84 after the first injection; days 28 and 84 corresponded to pre-injection troughs. CAB plasma concentrations were quantified by liquid chromatography-tandem mass spectrometry (lower limit of quantification, 40 ng/mL) and categorized according to the protein-adjusted (PA) IC90 (166 ng/mL) and 4×PA-IC90 (664 ng/mL). A multilevel regression model was fitted to log-transformed CAB concentrations, with visit day as a categorical predictor and participant-level characteristics (age, BMI, ethnicity) as covariates.

Sixty-four male participants initiated CAB-LA PrEP (median age, 37 years [IQR 32-42]; median BMI, 24.0 kg/m² [IQR 22.2-26.4]). All participants had concentrations above the PA IC90 at every time point. Median CAB concentrations were 637 ng/mL (IQR 448-1568; 50% >4×PA-IC90), 966 ng/mL (IQR 616-1895; 71.4%), 936 ng/mL (IQR 582-1739; 67.7%), and 1480 ng/mL (IQR 1067-2006; 93.8%) on days 3, 7, 28, and 84, respectively. Higher BMI was inversely associated with CAB concentrations (β = -0.044; 95% CI, -0.080 to -0.009; p = 0.016).

CAB-LA PrEP achieved protective plasma concentrations within the first week of initiation and demonstrated consistent accumulation with subsequent injections.