Optimal Management
The optimal management of these severe cases in PLWH remains unknown. However, based on the available published data summarized above, recommendations from the CDC and our institutional experience, we make the following recommendations on the management of severe mpox in PLWH.
  1. Upon identification of severe mpox in PLWH, we recommend consultation with CDC and local health departments, and immediate initiation of tecovirimat in combination with VIGIV and either cidofovir or brincidofivor if these agents are available and not contraindicated. While CDC guidance makes the addition of multiple agents a consideration, we feel strongly that a combination of agents should be employed to maximally inhibit viral replication while the immune system regains the ability to clear the virus. None of the available agents is viricidal, and therefore management should aim for maximal inhibition, effectively ‘bridging’ the host into a reconstituted state. This strategy also employs the theoretical benefits of protecting against resistance that may result from active viral replication in the presence of a single inhibitor, as well as antiviral synergy. These agents should be continued at least until lesions stop progressing and begin healing, which may take several weeks to months.
  2. Eligible patients should be encouraged to enroll the STOMP Trial and VIRISMAP, as combination antivirals against mpox does not exclude patients from these studies.
  3. ART should be initiated as soon as feasible, and in accordance with other HIV management guidance. While data are scarce, there appears to be no benefit to delaying ART to attenuate possible IRIS.
  4. Patients should be evaluated for alternative etiologies of their disease, as well as concomitant sexually transmitted infections and opportunistic infections as recommended by other HIV management guidance.
  5. Providers should perform a thorough history and physical examination to identify all possible organ systems that may be affected but may not be immediately apparent; these include musculoskeletal, ocular, central nervous system, gastrointestinal, pulmonary, and cardiovascular systems.
  6. In patients with suspected bacterial infection, providers should obtain appropriate cultures and then provide empiric antibiotics. The duration of empiric antibacterial therapy should be no longer than what would be given for the specific diagnosis that is suspected (ie SSTI or bacteremia) if the suspected diagnosis cannot be ruled out. Antibiotics should not be given indefinitely. While bacterial superinfection of mpox patients is low in the general population, patients with uncontrolled HIV and severe disease have higher incidence of bacterial superinfection. Bacterial infection resulting in sepsis can also be a significant cause of death in these patients, particularly those with anogenital and gastrointestinal lesions.
  7. Patients should be closely reassessed longitudinally over the full course of their recovery. As these severe mpox patients progress, they often develop fevers, leukocytosis, progression of lesions and new symptoms over the course of their management. Based on the heterogeneity of published cases, it is not clear if this progression represents the natural course of the disease in severely immunosuppressed hosts, or if there is a true development of IRIS. In the limited data available, there does not appear to be a significant difference in outcome among those who received IRIS treatment and those who did not; nor does there appear to be any benefit to delaying ART initiation.
  8. Care should be provided with a multidisciplinary approach to comprehensively and longitudinally address the multiple complex issues that stem from severe MPXV infection as well as any potential barriers to treatment adherence upon discharge. Specialties likely to be involved include: Infectious Disease, Internal Medicine, Pharmacy, Nursing, Wound Care, Pain and Palliative Care, Neurology, General Surgery, Orthopedic Surgery, Urology, Plastic Surgery, Ophthalmology, Dermatology, OBGYN, Psychiatry and Social Work. Quality wound care provided by a specialist is a critical component to this longitudinal care.