What is the recommended treatment for monkeypox infection, including first‑line antiviral therapy and supportive care?

Treatment for Monkeypox

Supportive care is the backbone of monkeypox treatment, with antiviral therapies (tecovirimat as first-line, brincidofovir or cidofovir as alternatives) reserved for severe disease, immunocompromised patients, or those with complications. 1, 2

First-Line Management: Supportive Care

Most monkeypox cases are self-limited and require only symptomatic management 1, 2:

• Pain control is essential, as lesions can be extremely painful, particularly genital, rectal, and oral lesions 3
• Skin care focuses on preventing secondary bacterial infection and promoting healing 1
• Hydration and nutrition support, especially when oral or esophageal lesions impair intake 3
• Fever management with antipyretics as needed 2

The illness typically resolves over 2-4 weeks as skin lesions progress through macules, papules, vesicles, pustules, and finally scab formation 1, 4

Antiviral Therapy Indications

No FDA-approved treatments exist specifically for monkeypox, but several antivirals developed for smallpox are available through expanded access programs 1, 2:

When to Consider Antivirals 3:

• Severe immunocompromise (particularly CD4 count <200 cells/μL in HIV patients)
• Severe manifestations including:
  • Ocular lesions
  • Neurologic complications (encephalitis)
  • Myopericarditis
  • Extensive mucosal involvement (oral, rectal, genital, urethral)
  • Uncontrolled viral spread
  • Hemorrhagic disease

Antiviral Options

Tecovirimat (ST-246) 2, 3, 5:

• First-line antiviral choice
• Orally bioavailable
• Targets viral egress by inhibiting the F13L gene product
• Available through expanded access or clinical trials
• Well-tolerated with minimal adverse effects in Phase I/II trials 6
• Dosing typically 600 mg twice daily for 14 days (weight-based adjustments may apply)

Brincidofovir 2, 3, 5:

• Alternative antiviral option
• Lipid ester of cidofovir with improved oral bioavailability
• Less nephrotoxic than cidofovir
• Available through expanded access programs

Cidofovir 6, 2, 3:

• Second-line therapy due to significant nephrotoxicity
• Requires IV administration with aggressive hydration and probenecid
• Dose: 5 mg/kg IV once, with potential second dose after 1 week if no response 7
• Major toxicity: Irreversible renal failure, neutropenia, metabolic acidosis 7
• Reserved for cases where other options have failed

Vaccinia Immune Globulin Intravenous (VIGIV) 4, 3, 5:

• Used for severe complications, particularly in immunocompromised patients
• Available through CDC consultation
• May be combined with antivirals for severe cases 6

Combination Therapy

For critically ill or severely immunocompromised patients, combination therapy with tecovirimat plus VIGIV has been used successfully 6, 3. A case report documented successful treatment of severe eczema vaccinatum using ST-246, CMX001 (brincidofovir), and VIGIV together 6.

Special Considerations

Immunocompromised patients (especially those with advanced HIV) have higher mortality risk (<0.2% overall, but significantly higher in this population) and should be considered for early antiviral therapy 1, 3

Ocular involvement requires ophthalmology consultation and may need topical trifluridine ophthalmic solution in addition to systemic antivirals 3

Infection control is critical: isolate patients until all lesions have crusted and separated, as viral shedding occurs throughout the illness 1

Accessing Therapeutics

In the United States, therapeutic medical countermeasures are accessed through 3:

• CDC consultation line (available 24/7)
• State health departments
• Expanded access protocols
• Clinical trials when available

Important caveat: The evidence base for antiviral efficacy in human monkeypox remains limited, derived primarily from animal models, case series, and experience with related orthopoxviruses 2, 3. Randomized controlled trials are urgently needed to establish definitive treatment guidelines 3.