LAUSR

A decade has passed since the World Health Organization (WHO) first recommended daily oral pre-exposure prophylaxis (PrEP) as an additional HIV prevention option [1]. The global potential for PrEP to reduce new HIV infections has yet to be realized. An estimated 1.5 million new HIV infections occurred in 2020, a decline of only 31% since 2010 and significantly below the 75% reduction target [2]. Scale-up of oral PrEP has begun to accelerate [3], yet only 28% of the 3 million PrEP users target for 2020 was reached [2]. Important advances in PrEP delivery are now beginning to expand access and uptake, including differentiated service delivery [4] and greater choices, including event-driven oral PrEP, and the first long-acting PrEP product, the dapivirine vaginal ring [5]. However, to further expand HIV prevention coverage and reduce new infections, rapid scale-up of existing PrEP options and the introduction of additional PrEP products, alongside other HIV prevention interventions, are urgently needed. Long-acting injectable cabotegravir (CAB-LA) is a new, safe and highly efficacious additional PrEP choice. Results from two randomized controlled trials (HPTN 083 and HPTN 084) suggested an estimated 66% relative reduction in HIV risk among cisgender men and transgender women who have sex with men [6] and 88% reduction among cisgender women compared with oral PrEP [7]. Long-acting injectable products have been found to be acceptable and often preferred in studies examining community PrEP preferences [8–12]. As such, CAB-LA may reach new clients for HIV prevention and be a more acceptable choice for people who have concerns about oral PrEP or other prevention options or difficulty taking these as prescribed. In July 2022, WHO is releasing a recommendation about the use of CAB-LA for PrEP to encourage availability in lowand middle-income countries (LMICs) and support inclusion in national guidelines and PrEP programmes [13]. This WHO recommendation will let manufacturers apply for inclusion on the WHO list of prequalified medicinal products, allowing agencies, such as the Global Fund, UNICEF and Unitaid, to procure CAB-LA. However, important issues regarding use in LMICs remain unresolved, and a bold programme of implementation research is urgently needed for CAB-LA to be implemented acceptably, safely and effectively at scale to achieve significant impact. Current experience with CAB-LA provision is largely limited to clinical trial settings. Evidence is lacking about effective models for providing CAB-LA in real-world settings, especially for populations either not included or under-represented in the trials, including sex workers, people who inject drugs and transgender men, and others living in diverse settings and geographies. There is also a need for further studies to support obtaining additional data about CAB-LA safety in some populations. While pharmacokinetic analyses did not show any clinically relevant effect by gender [14], research needs to ensure that there is no interaction between CAB-LA and genderaffirming hormone use among trans and gender diverse populations. Alternative injection sites should be considered for those unable to receive intramuscular gluteal injections, such as those with buttock implants. In addition, the acceptability, feasibility, safety and training needs for individuals to self-administer injections could be explored. This approach has been acceptable and feasible in other contexts, including for hormone injections, and may increase convenience and acceptability of CAB-LA and reduce service visits. Furthermore, while the limited evidence available suggests that CAB-LA is safe during pregnancy and breastfeeding, further large-scale implementation and post-market surveillance will be needed to understand whether there are any serious adverse events associated with CAB-LA use during pregnancy and breastfeeding. Where to deliver CAB-LA for maximum impact and acceptability must also be explored, including sexual and reproductive health services, anteand post-natal services, and community settings. Differentiated service delivery models have been crucial to oral PrEP access globally by providing personcentred services, adapted to the needs and preferences of individuals and communities. CAB-LA must be offered as a choice alongside a range of HIV prevention options, including oral PrEP, and must not create additional barriers to service access or reduce integration in settings where task-sharing with non-physician providers is important, such as community-