In healthy men with a low risk of HIV-1 infection, cabotegravir, an HIV-1 integrase strand transfer inhibitor with antiviral activity, was safe and well tolerated despite having a high number of mild-to-moderate injection site reactions, and was found to have suboptimal exposure when dosed 800mg every 12 weeks.

• Phase 2a study conducted at 10 sites in the US evaluated the safety, tolerability, and pharmacokinetics of long-acting cabotegravir in healthy men aged 18-65 years with low risk of acquiring HIV-1
• 127 patients were randomized (5:1) to receive cabotegravir (n=106) or placebo (n=21)
• Dosing regimen of cabotegravir: 30mg daily given orally for 4 weeks, 1 week washout period, and, after a safety assessment, 3 intramuscular injections of 800mg of long-acting cabotegravir every 12 weeks
• Double-blind procedure utilized until time of last injection (week 41 of the study)
• Primary endpoint: safety and tolerability (monitored from time of first injection to 12 weeks after last injection)
• Analyzed the “safety population”, defined as all patients who received 1 dose of study drug

• 99% of patients (126/127) comprised the safety population
• 83% of patients (106/127) were men who have sex with men (MSM) and 56% of patients (71/127) were white
• 82% of cabotegravir patients (87/106) and 95% of placebo patients (20/21) completed the injection phase
• Most common reasons for withdrawal from the study in the cabotegravir group: adverse events (7%) and injection intolerability (4%)
• 80% of long-acting cabotegravir patients (75/106) experienced an adverse event grade 2 or higher vs 48% of placebo patients (10/21; P=0.0049)
• Grade 2 or higher adverse events: injection-site pain (59%)
• For injections 1, 2, and 3, geometric mean trough plasma concentrations were reported as 0.302 g/mL (95% CI: 0.237, 0.385), 0.331 g/mL (95% CI: 0.253, 0.435), and 0.387 g/mL (95% CI: 0.296, 0.505), respectively
• Geometric mean apparent terminal phase half-life: 40 days
• 1 patient in each group acquired HIV-1 infection; occurred in the cabotegravir patient “24 weeks after the final injection when cabotegravir exposure was well below the protein-binding-adjusted 90% inhibitory concentration”