Should mpox be an AIDS-defining disease?

A severe necrotizing form of mpox with a high mortality rate among people with HIV whose CD4 count was less than 200 cells/m³ was described at CROI 2023, in Seattle (presentation 173). The investigators think mpox should be classified as an AIDS-defining disease.

“The first key finding that we have is there was a very clear relationship between CD4 count, viral load and outcomes,” said Chloe Orkin, MBBCH, MSc, a professor of HIV medicine in the Center for Immunobiology at the Blizard Institute, Queen Mary University of London, who presented the data. “We had 27% of people with CD4 counts less than 100 cells/m³ who died. Importantly, there were no deaths at all with CD4 counts above 200, which is the threshold at which we considered these conditions to be opportunistic infections and AIDS defining.”

Most mpox infections during this multicountry outbreak have been among men who have sex with men, and up to 50% of people diagnosed with mpox in 2022 had HIV. Most of them have well-controlled disease and low viral loads because they are on antiretroviral treatment (ART), according to Dr. Orkin.

Dr. Orkin and her colleagues reviewed the cases of 382 people with advanced HIV and mpox that were provided by SHARE-net clinicians from 19 countries. The cases included 27 of the 60 people who died of mpox during the outbreak. Among these patients, they found severe, necrotizing skin lesions; high rates of severe infections; and in some cases, unusual lung lesions and ocular disease (Lancet 2023;401[10380]:939-949).

“The key manifestation was this very severe disseminated necrotizing coalescing skin disease, and the disease was very far away from the site of entry,” she said.

“Unlike what we’ve seen previously where you get lesions around the site where the virus entered, these lesions were all over the body,” she explained. In addition, they found respiratory disease with nodules, as well as ocular disease that presented as periorbital edema and cellulitis. This indicates the disease is perivascular, according to Dr. Orkin, rather than being contained in the skin.

“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 prioritize the vaccination of people living with HIV, particularly in countries with low levels of diagnosis or without universal free access to antiretroviral treatment,” said Oriol MitjÀ, MD, PhD, the first author and an associate professor of Infectious Disease and Global Health, Fight Infectious Diseases Foundation, University Hospital Germans Trias i Pujol.

Of those who died:

• nearly 95% of people with low CD4 counts had necrotizing disease;
• just under 90% had respiratory disease;
• around 90% had both septicemia and secondary infections; and
• about 50% had ocular manifestations.

This form of mpox carries a 15% mortality in people with advanced HIV disease. All 27 deaths occurred within this group, the clinicians found.

Dr. Orkin also noted the low level of vaccination among these patients. “Nobody who received vaccination died, but it was a pitiful amount of people who received vaccination,” Dr. Orkin said. “Regarding tecovirimat [TPOXX, SIGA Technologies], 16% of people received tecovirimat. Some people received multiple courses, and 10 of the 27 people who received tecovirimat died.”

Both physicians recommended that public health officials work to vaccinate more people against mpox.

Although some people were not adherent to their ART, others did not know they were HIV-positive, and so she suggested that patients with mpox who do not know their HIV status be tested. Eighty-five people were started or restarted on antivirals when they were being treated for mpox because only 50% of the entire cohort had undetectable viral loads.

“Of this group of people, only 9% of the whole cohort were newly diagnosed. So we are talking about people who were diagnosed but not adherent to antiretroviral treatment,” she said.

AIDS-defining conditions are a group of conditions that are serious and life-threatening for people with advanced HIV, which is defined as a CD4 count of less than 200 cells/mm³.

Adding this severe form of mpox to the existing list of AIDS-defining conditions will help healthcare professionals protect people who are most at risk for death from mpox infection, she said.

“Clinicians use it; specialists, nonspecialist clinicians use [the definition] to guide clinical management, including the use of specific chemoprophylactic agents. It is also used to unlock healthcare benefits in many countries in the world because having an AIDS-defining condition means that you have access to housing and various other things. So, this classification has utility.”

All people with mpox should be tested for HIV, and all at-risk people with HIV should be prioritized for preventive mpox vaccination and antivirals. A global effort is needed to ensure access to antivirals and vaccines in countries where the interaction of uncontrolled HIV infection and mpox is more prevalent.

“The recent case series makes a very compelling case that in people living with HIV and with a CD4 count less than 200 cells/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,” said Meg Doherty, MD, PhD, the director of the WHO’s Global HIV, Hepatitis and Sexually Transmitted Infections Programmes, in a statement. The World Health Organization will review the data to assess whether severe mpox in people living with HIV is a marker for advanced HIV disease.

“It’s an AIDS-defining condition, and it should be added to the list of infections which are known to cause either disseminated infections or opportunistic disease,” Dr. Orkin reiterated.

By Marie Rosenthal, MS