SEATTLE — Among people living with HIV, a severe form of mpox in the context of immunosuppression appeared to lead to complications and even death, according to a global case series.

In a cohort of 382 patients, severe complications most commonly occurred in those with a CD4 cell count <100 cells/mm³ compared with those with a count of >300 cells/mm³, and included:

• Necrotizing skin lesions (54% vs 7%)
• Lung involvement with and without nodules (29% vs 0%)
• Secondary infections and sepsis (44% vs 9%)

Overall, 28% of patients were hospitalized, 25% of whom died, reported Chloe Orkin, MD, of Barts Health NHS Trust in London, during the Conference on Retroviruses and Opportunistic Infections.

The study was also published in The Lancet.

All deaths occurred in patients with CD4 counts <200 cells/mm³, with a median CD4 count at the time of death of 35 cells/mm³. “Almost all who died had a detectable viral load,” Orkin said. Moreover, nearly 90% of those who died had respiratory disease.

“Importantly, there were no deaths at all with CD4 counts above 200 cells/mm³, which is the threshold at which we consider disease conditions to be opportunistic infections and AIDS-defining,” Orkin noted.

In addition, “immune reconstitution inflammatory syndrome was suspected in a quarter of those starting or re-initiating antiretroviral therapy [ART] after mpox diagnosis — 57% of whom died,” she said.

Of note, only 26 people were vaccinated against mpox — 21 were given pre-exposure prophylaxis and five were vaccinated post-infection.

John Brooks, MD, of the Division of HIV/AIDS Prevention at the CDC, told MedPage Today that “for people with HIV, mpox can be life-threatening, it causes horrific morbidity. That’s why, since September 2022, mpox has been included in the CDC, NIH, and IDSA [Infectious Diseases Society of America] opportunistic infection guidelines.”

“We don’t talk about AIDS opportunistic infections. We talk about HIV opportunistic infections. My personal and professional experience is that people don’t like using the word AIDS anymore. That means I’m going to die. I’m hopeful that change in terminology will help us recognize this is no longer a life-threatening disease,” he said.

Orkin said that the severe mpox seen in this population warrants a call for classifying it as an AIDS-defining condition in CDC and WHO HIV disease classifications.

However, in an editorial comment, Isaac Núñez, MD, and Sergio Iván Valdés-Ferrer, PhD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, expressed concern about labeling the severe forms of mpox as AIDS-defining.

“Currently, ART is recommended for every person living with HIV, such that labeling fulminant mpox as an AIDS-defining condition will not modify this guidance,” they wrote.

“Unfortunately, the label of AIDS — from cultural, religious, or even lifestyle perspectives — continues to be stigmatizing. Labeling fulminant mpox as an AIDS-defining condition could have the unintended potential of sparking further stigma around both mpox and HIV,” they continued. “This stigma is so central to the global outbreak that monkeypox came to be called mpox, precisely to reduce discrimination regarding race and sexual orientation. Considering mpox in general as an opportunistic infection (a term that applies to any-cause immunosuppression and not only HIV) rather than labeling fulminant mpox as an AIDS-defining condition could have the same positive connotations regarding bedside care (e.g., increasing suspicion of other opportunistic infections) and preventing stigma.”

For this global case series, Orkin and colleagues included 382 patients (367 cisgender men, four cisgender women, and ten transgender women) from 19 countries. Median age was 35, 91% were known to be living with HIV, 65% were adherent to ART, and 8% had a concurrent opportunistic illness.

Median CD4 cell count was 211 cells/mm³; 22% had CD4 cell counts <100 cells/mm³ and 25% had counts of 100 to 200 cells/mm³. Overall, 51% had an undetectable viral load.

Sixteen percent of patients had received tecovirimat (Tpoxx), and 2% had received cidofovir or brincidofovir (Tembexa). Tecovirimat resistance was reported in three patients.

Orkin and team noted that their data were derived from an observational retrospective convenience case series from countries with high numbers of mpox infections; therefore, they were unable to assess how well the study cohort represented the entire population of people living with HIV who developed mpox infection. Moreover, participants had other infections that may have influenced outcomes.

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