Injection-site pain after long-acting rilpivirine: No association with tempering time in a prospective observational...

Long-acting injectable Rilpivirine (RPV-LA) is an essential component of current HIV maintenance therapy. Local injection-site reactions, particularly pain, are common and may influence treatment adherence. The product label advises allowing vials to reach room temperature before administration, although here is limited clinical evidence to support this practice.

We conducted a prospective observational study to assess whether the time elapsed between removing the RPV-LA vial from refrigerated storage and intramuscular injection ("tempering time") was associated with the intensity of pain at the injection site. Pain was recorded immediately after administration using a 0-10 visual analogue scale (VAS) and on days 3 and 5. Tempering time was measured in minutes. Linear regression and mixed-effects models assessed the relationship between tempering time and pain, adjusting for demographic and clinical factors.

A total of 179 participants contributed 195 injections. The median tempering time was 85 minutes (IQR 50-150). Median immediate pain score was 4.0 (IQR 2.0-6.0). In univariable analysis, longer tempering time was associated with lower pain (r = -0.31; 95% CI -0.56 to -0.03; P = 0.03). However, in multivariable analysis adjusting for tempering time, age and number of injections, the association was attenuated and no longer statistically significant (β = -0.27; 95% CI -0.59 to 0.06; P = 0.11). Age remained independently associated with lower pain scores (β = -0.03; 95% CI -0.05 to -0.01; P = 0.01). No associations were observed on days 3 or 5 post-injection.

In this real-world cohort, tempering time of RPV-LA was not independently associated with injection-site pain. Age was the only consistent predictor of pain intensity. These findings suggest that strict adherence to tempering recommendations may not substantially influence patient comfort. Further randomized studies are warranted to confirm these observations and explore additional strategies to minimize injection-site discomfort.