Introduction
Mpox virus (MPXV) is a large double-stranded DNA virus that causes a febrile illness with rash in humans. Until recently, MPXV caused sporadic zoonotic outbreaks primarily in Africa. However, in May 2022, a cluster of non-travel-related cases of human mpox were reported in the United Kingdom. Since those initial infections, the outbreak has spread world-wide infecting over 85,000 patients and causing over 100 deaths. Early outbreak data suggested no significant difference in outcome among people living with Human Immunodeficiency Virus (PLWH, HIV) and those without HIV. However, subsequent data have shown the majority of severe and fatal cases of human mpox infection occur in those with advanced HIV. It is now clear that advanced HIV is a significant risk factor for severe mpox and death, and that Immune Reconstitution Inflammatory Syndrome (IRIS) may play a role in these outcomes.
While the number of new mpox cases has dropped significantly since the outbreak began, recent case clusters suggest ongoing community transmission. This continued circulation poses an ongoing threat to susceptible hosts. Risk factors for progression of disease other than advanced HIV, natural progression of disease, and optimal management remain undefined. While the STOMP Trial and VIRISMAP are actively enrolling patients to address these questions, the decline in cases worldwide (a positive development overall) has stymied hopes of rapid answers. Given the rare occurrence of this infection in the outbreak’s current phase, and the absence of clinical trial data to address treatment for the most severe cases, optimal management will require vigilant multidisciplinary collaboration between the specialties involved in the care of these patients. This review summarizes the pathogenesis of mpox, available clinical data, identifies knowledge gaps and proposes recommendations on the management of these most severe cases among patients with advanced HIV with an emphasis on early combination antivirals and longitudinal wound care.