Background: Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor, available as a long-acting injectable nanosuspension, under development for HIV treatment and prevention.
Methods: HPTN 077 is a Phase 2a, randomized double-blind placebo-controlled study of CAB at two doses. Participants were low-risk HIV-uninfected individuals at eight sites globally, randomized (3:1) to daily oral CAB 30mg (or placebo [PBO]) for four weeks(W), followed by CAB (or PBO) 800mg IM at W5, 17, and 29 (Cohort 1[C1]) or 600 mg IM at W5, 9, 17, 25, and 33 (Cohort 2[C2]).
Results: 110 participants enrolled in C1, 89 in C2. Median age 31y (IQR: 24,40), BMI 27 (IQR: 23,32), 66% female, 41% Black, 27% White, 24% Latino, 8% mixed/other. Overall, 94% completed the oral phase, 89% received at least one injection, and 75% completed all injections, which did not differ by arm, cohort or sex (Table). Over 41W, injection site pain and injection site reactions (ISR) were more common in CAB vs. PBO. No other differences were found in safety or tolerability. ISR led to injection discontinuation in 2/134 (1.5%).

Table. Outcomes of Study PPTs by Cohort/Sex
[Table. Outcomes of Study PPTs by Cohort/Sex]

One seizure (participant with previous seizures) and one seroconversion (48W post last injection) occurred in CAB participants; CAB levels at the time of events were 278 ng/mL and < 25 ng/mL (LLQ), respectively. C2 dosing consistently achieved plasma trough targets; C1 dosing did not (Figure).

Figure. Geometric Mean Conc and 90% Pred Interval
[Figure. Geometric Mean Conc and 90% Pred Interval]

Conclusions: CAB was well tolerated among low-risk HIV-uninfected men and women. Pharmacokinetics support the development of CAB for HIV prevention using 600mg IM every 8 weeks with a 4-week loading dose for all sexes.