On Jul. 28, 2022, the World Health Organization (WHO) released new guidelines for the use of long-acting injectable cabotegravir (CAB-LA) as pre-exposure prophylaxis (PrEP) for HIV and called for countries to consider this safe and highly effective prevention option for people at substantial risk of HIV infection.

CAB-LA is an intramuscular injectable, long-acting form of PrEP, with the first 2 injections administered 4 The guidelines, released ahead of the 24th International AIDS Conference (AIDS 2022), will support countries as they plan for CAB-LA introduction as part of a comprehensive approach to HIV prevention and will facilitate urgently needed operational research.

The guidelines are launched at a critical moment, as HIV prevention efforts have stalled with 1.5 million new HIV infections in 2021 – the same as 2020. There were 4000 new infections every day in 2021, with key populations (sex workers, men who have sex with men, people who inject drugs, people in prisons and transgender people) and their sexual partners accounting for 70% of HIV infections globally.

CAB-LA is an intramuscular injectable, long-acting form of PrEP, with the first 2 injections administered 4 weeks apart, followed thereafter by an injection every 8 weeks. CAB-LA was shown to be safe and highly effective among cisgender women, cisgender men who have sex with men, and transgender women who have sex with men in 2 randomized controlled trials, HPTN 083 and HPTN 084. Together, these landmark studies found that use of CAB-LA resulted in a 79% relative reduction in HIV risk compared with oral PrEP, where adherence to taking daily oral medication was often a challenge. Long-acting injectable products have also been found to be acceptable and sometimes preferred in studies examining community PrEP preferences.

Consistent with previous WHO guidelines, the new CAB-LA guidelines are based on a public health approach that considers effectiveness, acceptability, feasibility and resource needs across a variety of settings. The guidelines are designed to facilitate CAB-LA delivery and the operational research which is urgently needed to address implementation and safety issues. These will inform decisions on how to successfully provide and scale up CAB-LA. The guidelines highlight critical research gaps, including issues relating to HIV drug resistance, HIV testing, service delivery models, resource requirements, safety in pregnancy and breastfeeding, and provision of CAB-LA in geographies and for populations not included in the trials.