What is the recommended Mpox vaccine regimen for a patient with HIV who is at high risk of exposure due to frequent sex at a bathhouse?

Mpox Vaccination for High-Risk HIV-Positive Patient

This patient should receive two doses of the Mpox vaccine (JYNNEOS) separated by four weeks (Answer A). 1, 2

Rationale for Two-Dose Regimen

The standard JYNNEOS vaccination schedule consists of two doses administered 28 days (4 weeks) apart via subcutaneous injection, which is the FDA-approved regimen for mpox prevention 1, 2. This patient meets high-risk criteria as a man who has sex with men (MSM) with multiple sexual partners in high-risk venues (bathhouse), making him a priority candidate for the complete two-dose series 2.

Evidence Supporting Two Doses Over One Dose

Two doses provide superior protection compared to a single dose:

• Vaccine effectiveness against mpox infection: Two doses provide 82% effectiveness (95% CI 72-92%) compared to 76% effectiveness (95% CI 64-88%) for one dose 3, 4
• Protection against hospitalization: Among persons with mpox, those who received 2 doses had odds of hospitalization of 0.20 (95% CI 0.01-0.90) compared to unvaccinated individuals 5
• Critical for HIV-positive patients: In mpox patients with HIV infection specifically, completing the 2-dose series is especially important as no hospitalizations were identified among HIV-positive persons who received both doses 5

Why Other Options Are Incorrect

Option B (single dose two weeks before exposure) is inadequate because:

• A single dose provides only 35.8% effectiveness (95% CI 22.1-47.1) 3
• The patient requires ongoing protection given continuous high-risk behavior, not just pre-event prophylaxis 2
• Two weeks is insufficient time even for single-dose protection to develop fully 1

Option C (annual booster) is not currently recommended as there is no established annual booster schedule for mpox vaccination in routine immunization programs 2. Current guidance focuses on completing the primary two-dose series 1, 2.

Option D (contraindication due to live vaccine) is incorrect because JYNNEOS is a non-replicating Modified Vaccinia Ankara (MVA) vaccine, not a live replicating vaccine like the older smallpox vaccines 1, 3. HIV infection is not a contraindication to JYNNEOS vaccination 5.

Implementation Protocol

Vaccination schedule:

• Administer first dose immediately 2
• Administer second dose 28 days (4 weeks) after the first dose 1, 2
• Either subcutaneous (0.5 mL) or intradermal (0.1 mL) administration is effective 1

Special considerations for HIV-positive patients:

• No CD4 count threshold is required for JYNNEOS administration (unlike older live vaccinia vaccines) 5
• Completing both doses is particularly important in this population to optimize protection against severe disease and hospitalization 5
• The patient should be counseled that maximum protection occurs ≥14 days after the second dose 1

Common Pitfalls to Avoid

• Do not delay the second dose beyond 4 weeks without medical necessity, as this may compromise optimal immunity 2
• Do not confuse JYNNEOS with older live vaccinia vaccines (like Dryvax), which were contraindicated in immunocompromised patients 6
• Do not assume one dose is sufficient for high-risk individuals, especially those with HIV 5, 3
• Do not recommend post-exposure prophylaxis (PEP) as primary strategy for someone with ongoing high-risk behavior, as PEP effectiveness is only 20% (95% CI -24-65%) 4