The retrovirus HIV-1 is the etiological agent of the decades-long AIDS pandemic. 
Although vaccination is the most common preexposure route to prevent acquisition 
of viral disease, scalable efficacious vaccination strategies have yet to be 
developed for HIV-1. By contrast, small molecule inhibitors of the HIV-1 enzymes 
reverse transcriptase, integrase, and protease have been developed that 
effectively block virus replication. Three different drug compounds are commonly 
prescribed for people living with HIV as once-daily oral tablets. Once-daily 
pills composed of two different reverse transcriptase inhibitors are moreover 
approved as preexposure prophylaxis (PrEP) treatment for virus naïve individuals 
who may partake in behaviors associated with increased risk of HIV-1 acquisition 
such as unprotected sex or injection drug use. Long-acting (LA) injectable HIV-1 
enzyme inhibitors are at the same time being developed to sidestep adherence 
noncompliance issues that can arise from self-administered once-daily oral 
dosing regimens. Cabotegravir (CAB)-LA, which inhibits integrase strand transfer 
activity, has in recent clinical trials been shown to prevent HIV-1 acquisition 
more effectively than once-daily oral dosed reverse transcriptase inhibitors. In 
this Perspective, we examine bench to bedside aspects of CAB-LA treatment and 
development, starting from the biochemical basis of HIV-1 integration and 
pharmacological inhibition of integrase catalysis. We also review the results of 
recent clinical trials that evaluated CAB-LA, as well as the promises and 
challenges that surround its use for HIV/AIDS PrEP.