Point-of-care ultrasound guidance for long-acting cabotegravir-rilpivirine administration improves injection-site tolerability and preserves pharmacokinetics.

OBJECTIVE

Long-acting injectable cabotegravir + rilpivirine (CAB + RPV) streamlines HIV care but may be limited by injection-site reactions (ISRs) and pharmacokinetic (PK) variability. Point-of-care ultrasound (POCUS) can visualize tissue planes in real time, yet its impact on drug exposure and tolerability remains unclear.

DESIGN

This is a prospective crossover study in 51 virologically suppressed adults receiving bimonthly CAB + RPV who underwent one ventrogluteal injection guided by POCUS, followed by routine unguided ventrogluteal injections.

METHODS

Trough and one month postinjection plasma concentrations were quantified by LC-MS/MS. ISRs were evaluated with a validated questionnaire. Mixed-effects models compared PK and tolerability outcomes.

RESULTS

We analyzed 143 trough and 46 one month postinjection samples. Intramuscular deposition was confirmed in 75% of ultrasound-guided injections. Median trough and one month post injection concentrations for both CAB and RPV were comparable between ultrasound-guided and ultrasound-unguided injections. Notably, the proportion of CAB though concentrations below the PAIC90 threshold was higher in the ultrasound-unguided group (9.8% vs. 0%; P  = 0.001). Ultrasound guidance reduced the overall ISR burden by 16% [relative risk (RR) 0.84, 95% confidence interval (CI) 0.72-0.97; P  = 0.018], with fewer reports of induration (8% vs. 19%; P  = 0.026) and redness (6% vs. 15%; P  = 0.034).

CONCLUSIONS

These findings support ultrasound guidance as a practical approach to improve injection accuracy and patient comfort, particularly in individuals at higher risk of poor intramuscular deposition or prior tolerability issues.