Abstract and Introduction
Abstract
Background: Long-acting injectable cabotegravir (CAB-LA) represents a new additional option for HIV prevention in people at substantial risk of HIV infection that may fill the gaps in pre-exposure prophylaxis (PrEP) uptake, adherence, and retention in users having difficulty with oral PrEP. Data from clinical trials demonstrated that CAB-LA was safe, highly effective, and well-accepted for HIV prevention. However, the occurrence of breakthrough HIV infections despite timely injections, HIV seroconversion timing and patterns, risk of selection and dissemination of resistance-associated mutations to integrase inhibitors, complexity of follow-up, logistical considerations, and its cost effectiveness compared with oral PrEP constitute significant issues for the integration of CAB-LA into clinical routine.
Findings: These concerns need to be addressed before moving forward with large-scale implementation programmes. Pilot and implementation projects are required in the following areas: HIV testing algorithms, patient education, clinic procedures, protocols for switching and discontinuation, efficacy and safety in populations not included in clinical trials, and demedicalization processes. The development of models to increase the uptake of, adherence to, and persistence with and after CAB-LA injections will also be of paramount importance for success. Lessons learned from these projects will increase experience, staff expertise, and organizational and training capacities to support the roll-out of this new agent as part of HIV prevention programmes.
Conclusion: CAB-LA has not yet achieved its full potential in HIV prevention, and strong commitment from all stakeholders is required to push CAB-LA as a game-changer in HIV response.
Introduction
Over the last 10 years, pre-exposure prophylaxis (PrEP) for HIV has become the most important breakthrough in HIV prevention strategies. Randomized controlled trials have shown that oral tenofovir disoproxil (TDF)-based PrEP was highly effective for the prevention of HIV infection if adherence was high.[1–4] This led the World Health Organization (WHO) to recommend its use in all individuals at substantial risk of HIV infection in 2015.[5] After several years, compelling arguments suggest that PrEP deployment has contributed to a decrease in HIV incidence at the community level. In Australia, rapid and targeted PrEP roll-out among 3700 high-risk men who have sex with men (MSM) in a network of 21 clinical sites across New South Wales led to a 31.5% decline in recent HIV infections after 1 year.[6,7] Rolling out PrEP into HIV prevention programmes became a major priority of HIV prevention policy-makers, but there is still a long way to go to reach the Joint United Nations Programme on HIV/AIDS (UNAIDS) goals. In 2022, ~2.5 million people used PrEP worldwide, which represents only 7% of the new global 2025 target.[8,9] PrEP barriers are multi-dimensional and occur at each step of the PrEP care continuum.[10] Social, economic, and political interventions remain crucial to addressing these hurdles, but new PrEP regimens are also needed to improve PrEP adherence and acceptance. Long-acting agents and extended-release formulations are being developed to enhance PrEP adherence and coverage. These include long-acting (LA) injectables and oral agents, subcutaneous LA implants, and neutralising monoclonal antibodies.[11] In December 2021, the US Food and Drug Administration (FDA) approved LA cabotegravir (CAB-LA) for HIV prevention in the wake of the HPTN 083 and 084 clinical trial results.[12] The product is administered by providers as a single 600-mg intramuscular injection given at 2-month intervals after an initial two injections 1 month apart. As the first injectable antiretroviral drug (ART) available for PrEP, CAB-LA has the potential to be a game-changer in HIV prevention, but its positioning in the current HIV PrEP strategy remains to be defined.
HIV Medicine. 2023;24(6):653-663. © 2023 Blackwell Publishing
