Mpox: Exploring Epidemiology, Disease Outcomes, and Preventative Vaccination Among People with HIV During the Ongoing Outbreaks

Human mpox, caused by the mpox virus, is a reemerging viral zoonosis that has gained global attention due to recent Clade IIb outbreaks outside of Africa, as well as ongoing Clade Ia and Ib outbreaks in the Democratic Republic of Congo (DRC) and surrounding regions. Since the start of these outbreaks in 2022, approximately 160,000 people have been affected across more than 100 countries. People with human immunodeficiency virus (HIV; hereafter referred to as PWH) have been disproportionately affected, accounting for approximately 50% of all cases. Mpox is typically a self-limiting illness causing smallpox-like symptoms lasting 2-4 weeks, which can cause significant pain and morbidity. People with uncontrolled or advanced HIV face an elevated risk of severe mpox, secondary complications, and worse outcomes. Vaccination with second- and third-generation vaccinia-based smallpox vaccines has emerged as an important tool in mpox prevention, alongside behavioural modification to mitigate risk. However, only the third-generation, live-attenuated, non-replicating vaccine, modified vaccinia Ankara (MVA-BN [Bavarian Nordic]), is approved for use in PWH. Real-world estimates suggest that two doses of MVA-BN administered as pre-exposure prophylaxis confers vaccine effectiveness in the range of 66-90%. Additionally, MVA-BN has been widely demonstrated to have an acceptable safety profile. This narrative review explores the changing epidemiology, clinical manifestations, and outcomes of mpox in PWH. We also summarise evidence from the Clade IIb outbreaks on the effectiveness and safety of MVA-BN among PWH. Despite progress in our understanding, knowledge gaps persist regarding vaccine performance in individuals with advanced immunosuppression. Furthermore, due to the emergent nature of outbreaks in the DRC and surrounding areas, limited information is available regarding implications for PWH in the context of Clade Ia and Ib. We aim to provide healthcare providers, community stakeholders, and researchers with a foundational understanding of mpox in PWH and the role of MVA-BN in mpox prevention among this group, while highlighting areas of uncertainty. These insights may be helpful in the planning of future research and to inform strategies for the prevention and management of mpox among PWH, particularly those with advanced or uncontrolled HIV.