HIV Prevention with Intramuscular PrEP Regimen May Be Safe Option

Long-acting cabotegravir was found to be safe and well tolerated in men without HIV, according to a recent study.

The double-blind, randomized, placebo-controlled trial was conducted at 10 sites in the USA and included 127 healthy men who were not considered at a high risk for acquiring HIV. Most of the participants were men who had sex with men (83%). A total of 206 participants were assigned to receive cabotegravir and 21 were assigned to received matching placebos.
________________________________________________________________________________________________________________________________________
RELATED CONTENT
Bacterial vaginosis unlikely to reduce anti-HIV efficacy of oral tenofovir PrEP
WHO: Increasing Rates of Drug-Resistant HIV
________________________________________________________________________________________________________________________________________

During the lead-in phase, participants received either 30 mg oral tablets of cabotegravir or placebo tablets. After a 1 week washout period, intramuscular injections of long-acting cabotegravir at a dose of 800 mg or saline injections were administered every 12 week. The safety and tolerability of cabotegravir compared with placebo from the first injection to 12 weeks after the last injection (administered at 41 weeks) was assessed as the primary endpoint.

Overall, 87 participants (82%) in the cabotegravir group and 20 participants (95%) in the placebo group completed the injection phase.

Seven participants (7%) withdrew from cabotegravir treatment due to adverse events, and 4 participants (4%) withdrew due to injection intolerability. Those receiving long-acting cabotegravir experienced more grade 2 or higher adverse events compared with those in the placebo group (75 [80%] vs 10 [48%], respectively), mostly attributed to injection-site pain (n=55 [59%]). However, there were no significant differences in concomitant medications, laboratory abnormalities, electrocardiogram, or vital sign assessments.

In addition, geometric mean trough plasma concentrations for injections 1, 2, and 3, were 0.302 μg/mL, 0.331 μg/mL, and 0.387 μg/mL, respectively, which was lower than the predicted exposure. The geometric mean apparent terminal phase half-life estimated after the third injection was 40 days. During the injection phase, 2 men who had sex with men (2%) and 1 participant in the placebo group acquired HIV. One participant in the cabotegravir group acquired the infection 24 weeks after the final injection when cabotegravir exposure was below the protein-binding-adjusted 90% inhibitory concentration.

“Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile,” the researchers concluded. “Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated. Our findings support further investigation of long-acting injectable cabotegravir as an alternative to orally administered pre-exposure prophylaxis regimens.”

—Melissa Weiss

Reference:

Markowitz M, Frank I, Grant RM, et al. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial [published online May 22, 2017]. Lancet HIV. http://dx.doi.org/10.1016/S2352-3018(17)30068-1.