News & Media > BHIVA rapid guidance on monkeypox virus

BHIVA rapid guidance on monkeypox virus

Authors: Dr Laura Waters, Prof Marta Boffito, Dr Claire Dewsnap, Dr Jonathan Underwood, Dr Clare van Halsema and Prof Anna Maria Geretti

Publication date: 17 August 2022

Review date: 17 February 2023


Introduction

As of 8 August 2022, 3017 cases of monkeypox virus (MPV) have been reported in the UK, 96% in England with 71% of cases in England occurring in London residents. Gay and bisexual men who have sex with men (GBMSM) continue to be impacted disproportionately.

The UK Health Security Agency (UKHSA) epidemiological overview can be found here:
https://www.gov.uk/government/publications/monkeypox-outbreak-epidemiological-overview

Latest information on case definitions, vaccination and principles of infection control can be found here:
https://www.gov.uk/government/collections/monkeypox-guidance


Impact of HIV on MPV

Prior to the current outbreak the evidence as to how HIV impacts risk of MPV acquisition or its disease course was limited to two case series from Nigeria:

  • 118 MPV cases: 6% mortality rate; 4/7 deaths in people with HIV, at least three with advanced HIV and not on antiretroviral therapy (ART); total number of people with HIV not described [1].

  • 40 MPV cases (nine with HIV; at least seven with high viraemia and/or low CD4 counts): people with HIV experienced more prolonged illness, larger lesions and higher rates of both secondary bacterial skin infections and genital ulcers [2].

Another case series from the USA included 34 MPV cases, but HIV status was not reported; there were no deaths [3].

Since then, two large case series have been published, including:

  • 528 cases from 16 countries across five continents: 98% GBMSM and 41% living with HIV (96% on ART, 95% with viral suppression, median CD4 count 680 cells/mm3). Clinical presentation was similar among those with and without HIV, including frequency of hospital admission. Three people experienced serious complications: one case of epiglottitis in a person with HIV; two cases of myocarditis, one in a person living with HIV [4].

  • 181 cases from Spain: 92% GBMSM, 40% living with HIV of whom 11% had CD4 counts <500 cells/mm3. HIV status did not impact incubation period, clinical features or lesion number. Median time from lesion onset to dry crusting was 11 days (interquartile range [IQR] 8–14 days) for people with HIV versus 10 days (IQR 7–12 days) for people without HIV [5].

As of 16 August 2022, there have been 12 reported MPV-related deaths globally, with an overall mortality of 0.04% (1.9% and 0.015% in countries that have and have not reported MPV historically, respectively) [6]. Whether mortality in the 2022 outbreak is associated with immunosuppression, including HIV, remains unknown.

Currently, beyond vaccine considerations (see below), we do not recommend any specific actions for people living with HIV beyond vigilance about clinical presentations and history of exposure. We suggest that the following groups may be at higher risk of MPV infection and complications, and thus should be prioritised for specialist review. People with:

  • CD4 cell counts <200 cells/mm3

  • Recent HIV-related illness (e.g. AIDS diagnosis in the previous 6 months)

  • Persistent HIV viraemia (e.g. >200 copies/mL)

  • Concomitant conditions or treatments that may cause immune suppression.


Vaccine efficacy and safety considerations

There are two smallpox vaccines that also confer protection against MPV:

  • One prepared with live vaccinia virus, which is no longer available in the UK

  • The other an attenuated non-replicating vaccine, e.g. the MVA-BN (Imvanex) vaccine recommended by UKHSA [7].

Non-replicating smallpox vaccines can be used in line with existing BHIVA vaccine guidance [8]. The MVA-BN vaccine has been studied in people living with HIV and a CD4 count >100 cells/mm3. The vaccine can be used at CD4 counts <100 cells/mm3 although is likely to be less effective (particularly if the CD4 count is <50 cells/mm3); patients should receive specialist advice about protection from exposure.

A single dose of MVA-BN is recommended as post-exposure prophylaxis within 4 days of exposure for all. It should be considered up to 14 days post-exposure (for those not displaying symptoms) in those at higher risk of serious MPV infection. The Green Book defines all people living with HIV as immunosuppressed for vaccine purposes, regardless of CD4 count [9].

i-base has summarised the serological response rates to MVA-BN vaccines in people with and without HIV [10]. Key points from these studies are:

  • In a study of 151 people (91 with HIV, 97% on ART, CD4 ≥350 cells/mm3), MVA-BN vaccination was equally safe and well tolerated and yielded similar total and neutralising antibody kinetics, regardless of HIV status [11].
    - Vaccinia-naïve population, two vaccine doses 4 weeks apart: total/neutralising antibody seroconversion rates in people with HIV versus people without HIV were 83%/89% versus 78%/96% 2 weeks after one dose and 92%/91% versus 96%/93% 2 weeks after the second dose.
    - Though seroconversion rates were similar, antibody titres tended to be lower in people with HIV.
    - Vaccinia-experienced population (previously vaccinated against smallpox), one vaccine dose: 74–89% had low-level antibodies prior to vaccination, irrespective of HIV status. Antibody responses were boosted by the vaccine, with total and neutralising antibodies in ≥90%, regardless of HIV status.

  • In a study of 579 people (482 with HIV, median CD4 count 420 [range 200–750] cells/mm3) receiving at least one vaccine dose, total antibody seroconversion rates were high and similar regardless of HIV status [12]. Total antibody detection in people with HIV versus people without HIV:
    - Vaccinia-naïve, 4 weeks after first dose: 80% versus 86%
    - Vaccinia-naïve, 2 weeks after second dose: 98% versus 100%
    - Vaccinia experienced, 4 weeks after first dose: 93% versus 100%
    - Vaccinia-experienced, 2 weeks after second dose: 99% versus 100%.

    Although HIV status and baseline CD4 count had no impact on seropositivity rates, among vaccinia-naïve participants, antibody titres were significantly higher in HIV-negative people than in those with HIV at 2 and 4 weeks post-second vaccine dose; there was a trend towards lower titres with lower CD4 counts (data not included). There were no differences in antibody titres in vaccinia-experienced people by HIV status.

  • In one trial, 91% of people receiving MVA-BN developed neutralising antibodies by day 14 after a single vaccine dose; this study did not include people with HIV [13].

While serological vaccine responses may not fully reflect vaccine efficacy (e.g. via cell-mediated immunity), in the absence of clinical efficacy data we base our assumptions on the above seroconversion rates, whereby detectable antibodies are assumed to confer protection from infection and/or disease. This advice will be updated as and when new evidence emerges.

Based on the data outlined and experience with other vaccines, we recommend:

  • People with HIV who are vaccinia-naïve (i.e. never immunised against smallpox) are advised that vaccination will not be protective immediately; protection will be about 80% by 2 weeks after one vaccine dose and about 95% by 2 weeks after a second dose, i.e. maximum protection will take 6 weeks assuming two doses are given 28 days apart.

  • People who have received smallpox vaccination in the past can expect >90% protection within 2 weeks after a single vaccine dose and close to 100% within 2 weeks after a second dose.

  • All people with HIV should receive two full vaccine doses. While vaccine supplies are limited, people with a CD4 cell count <200 cells/mm3 or persistent viraemia should be prioritised to receive a full first vaccine dose, and to receive a second full vaccine dose as soon as available. The CD4 count cut-off will be kept under review.

  • People with detectable viraemia should be supported to achieve viral suppression to maximise vaccine efficacy.


Treatment: clinical, pharmacokinetic and renal considerations

There are three antivirals available to treat MPV:

1. Tecovirimat potential for drug–drug interactions (DDIs), see Liverpool website [14]

2. Brincidofovir (oral pro-drug of cidofovir): potential for DDIs, see Liverpool website [14]

3. Cidofovir high nephrotoxic potential; avoid nephrotoxic antiretrovirals (e.g. tenofovir disoproxil) and lack of data with tenofovir alafenamide warrants caution.

There are no guidelines for routine antivirals to treat MPV. Inpatient decisions should be made on a case-by-case basis. We encourage recruitment of people with MPV not requiring hospitalisation to relevant clinical trials.

BASHH provides several monkeypox resources, including management of proctitis, on their website (https://bashh.org/news/monkeypox-resources/).


References

1. Yinka-Ogunleye A et al; CDC Monkeypox Outbreak Team. Lancet Infect Dis 2019; 19: 872–879.

2. Ogoina D et al. Clin Infect Dis 2020; 71: e210–e214.

3. Huhn GD et al. Clin Infect Dis 2005; 41: 1742–1751.

4. Thornhill J et al. N Engl J Med 2022. doi: 10.1056/NEJMoa2207323.

5. Tarin-Vicente EJ et al. Lancet 2022; S0140-6736(22)01436-2. doi: 10.1016/S0140-6736(22)01436-2.

6. Centers for Disease Control and Prevention. 2022. Available at: https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html (accessed August 2022).

7. UK Health Security Agency. 2022. https://www.gov.uk/government/publications/monkeypox-vaccination (accessed August 2022).

8. BHIVA vaccine guidelines 2015. Available at: https://www.bhiva.org/file/NriBJHDVKGwzZ/2015-Vaccination-Guidelines.pdf (page 70) (accessed August 2022).

9. Green Book, chapter 7: immunisation of people with underlying medical conditions. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/857279/Greenbook_chapter_7_Immunsing_immunosupressed.pdf (accessed August 2022).

10. i-base. 2022. Available at: https://i-base.info/qa/20255 (accessed August 2022).

11. Greenberg RN et al. J Infect Dis 2013; 207: 749–758.

12. Overton ET et al. Open Forum Infect Dis 2015; 2: ofv040.

13. Pittman PR et al. N Engl J Med 2019; 381: 1897–1908.

14. University of Liverpool. 2022. Available at: https://www.hiv-druginteractions.org/checker (accessed August 2022).


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