Modern antiretroviral therapy has demonstrated effectiveness in preexposure 
prophylaxis (PrEP) and treatment of HIV infection. There is a demand for 
prevention and treatment regimens that could overcome challenges of improving 
adherence, toxicity, and dosing convenience. Cabotegravir is an integrase strand 
transfer inhibitor and an analog of dolutegravir. Unlike dolutegravir, 
cabotegravir has a long half-life and can be formulated into a long-acting 
nanosuspension for parenteral administration. Initial pharmokinetic studies in 
humans have demonstrated adequate drug levels with intramuscular (IM) 
administration at 4 weekly and 8 weekly intervals, with few interactions with 
commonly used concomitant medications. Preliminary animal PrEP studies have 
shown that IM cabotegravir can prevent simian/HIV acquisition from rectal, 
vaginal, and intravenous challenge. Currently, there are two ongoing Phase II 
studies assessing cabotegravir as a PrEP agent in humans: ÉCLAIR and HPTN077. 
Cabotegravir has been studied in combination with rilpivirine as long-acting IM 
maintenance therapy. The Long-Acting Antiretroviral Treatment Enabling study 
demonstrated that those switching to oral cabotegravir/rilpivirine once 
virologically suppressed were more likely to maintain suppression than those 
continuing standard efavirenz-based therapy (82% vs 71% at 24 weeks). Initial 
results of the Long-Acting Antiretroviral Treatment Enabling-2 study of 
parenteral regimens found that 12 weeks after randomization to parenteral or 
oral regimens, there was no difference in proportions virologically suppressed 
on cabotegravir/rilpivirine daily orally vs IM every 4 weeks or 8 weeks (91% vs 
94% vs 95%). The injections were well tolerated as, although they caused 
injection site pain in most recipients, most participants reported satisfaction 
with parenteral therapy. Cabotegravir offers a new member of the integrase 
strand transfer inhibitor class with potential for alternative mode of delivery. 
We await Phase III studies to define its efficacy and real-world experience to 
learn which patient groups stand to benefit most from the novel mode of delivery 
of treatment and PrEP.