Clinicians identify severe form of mpox with high mortality in people with advanced HIV

22 February 2023

The authors are calling for this form of mpox be added to the World Health Organization and Center for Disease Control list of severe infections that are considered particularly dangerous to people with advanced HIV disease. They also recommend that all people with mpox be tested for HIV.

An international collaboration of clinicians, who have previously published two seminal global case series on mpox has today (21 February) published the largest case series of mpox infection in people with advanced HIV disease in The Lancet, in which they identify a new severe form of mpox.

The majority of mpox infections in the current multi-country outbreak have occurred in sexual networks of gay, bisexual and other men who have sex with men. 38-50% of people diagnosed with mpox in 2022 also live with HIV, the vast majority of who are on HIV treatment and living healthy lives.  

Research from previous outbreaks in historically-affected countries and from small numbers of people in the current outbreak suggested that mpox infection may be more severe in people with advanced HIV. However, until now, there has been no large global study to examine this further.

The SHARE-net clinicians looked at 382 people with advanced HIV disease and mpox, including 27 of the 60 people (at the time of writing) reported to have died of mpox during the multi-country outbreak. The group describes a very severe form of mpox characterised by widespread, large, necrotising skin lesions; high rates of severe infections; and, in some cases, unusual lung lesions. This form of the disease carries a 15% mortality in people with advanced HIV disease and immunosuppression. All 27 deaths occurred within this group.

The study provides evidence that the disease is behaving differently and very concerningly in people with advanced HIV disease and immunosuppression, and the authors are calling for it to be added to AIDS-defining disease definitions set by the Center for Disease Control (CDC) and WHO that are used by clinicians worldwide to guide management.

AIDS-defining conditions are a group of conditions that are serious and life-threatening for people with advanced HIV-related disease. A person with HIV is defined as having advanced HIV-related disease when their CD4 cell count– a type of cell in the immune system – is less than 200 cells/mm3. A healthy person living with or without HIV has CD4 counts of over 500 cells/mm3. 

Adding this severe form of mpox to the existing list of AIDS-defining conditions will help healthcare professionals to protect immunocompromised people who are most at risk of dying from mpox infection. All people with mpox should be tested for HIV, and all at-risk persons with HIV and immunosuppression should be prioritised for preventive mpox vaccination and antivirals.

Most mpox deaths have occurred in countries where there are low levels of HIV diagnosis and/or without universal access to antivirals for mpox and/or HIV and without access to intensive care units. A concerted global effort is needed to ensure equitable access to antivirals and vaccines in countries where the interaction of uncontrolled HIV infection and mpox is more prevalent.

Research lead author Chloe Orkin, Professor of HIV Medicine at Queen Mary University of London and Director of the SHARE collaborative, said:

“Currently, there is a list of fourteen infections which behave differently and are particularly dangerous to immunosuppressed people with advanced HIV infection. These are called ‘AIDS-defining conditions’ by international public health agencies. Clinicians worldwide use this classification to guide their management of people most at risk of dying from these infections. We therefore call for mpox to be added to this list of ‘AIDS-defining conditions’ as it is an opportunistic infection. No new or emerging infections have been added to the CDC I-classification since 1993.”

Dr Meg Doherty, Director of Global HIV, Hepatitis and STI programmes, at the World Health Organization, said:

"The recent case series makes a very compelling case that in people living with HIV and with a CD4 count less than 200cells/mm3, the risk of severe disease and death from mpox is high and disseminated infection behaves like other opportunistic infections. This emphasizes the need for offering HIV testing for those with mpox and for people living with HIV to access early treatment, mpox vaccines, and antivirals in case of infection. Deaths can be prevented with early interventions. WHO will review relevant data with global experts to assess if severe mpox in people living with HIV is a marker for advanced HIV disease (AHD).”

Oriol Mitjà, first author and Associate Professor of Infectious Disease and Global Health, Fight Infectious Diseases Foundation, University Hospital Germans Trias i Pujol, said:

"We describe a severe form of mpox affecting mostly young men who have sex with men and which results in death in 15% of people with advanced HIV. When clinicians recognize necrotizing skin lesions and/or lung involvement, they should use a differentiated clinical pathway and an intensified approach. Also, health authorities should prioritise the vaccination of people living with HIV, particularly in countries with low levels of diagnosis or without universal free access to antiretroviral treatment."

Matthew Hodson, Executive Director of NAM aidsmap, said:

Our success in curbing new mpox infections may have led us to think mpox is no “longer a cause for concern. This data highlights that mpox remains a significant threat to the lives of people with advanced HIV, a group who may not be getting the healthcare they need, including mpox vaccination.

Although mpox is rarely severe for those of us whose HIV is controlled with treatment, the rates of serious illness and mortality as a result of mpox for people with untreated or unsuppressed HIV are worrying. This again highlights the urgency of ensuring people with HIV are diagnosed and have secure access to treatment. Routine HIV testing for all people diagnosed with mpox has the potential to reduce mpox-related deaths and advanced HIV disease. The progress we have made in our ability to treat HIV is a towering scientific achievement, we must ensure that all benefit.”