Global Case Series Characterizes Severe Form of Mpox in People With Advanced HIV

A global case series described a severe form of mpox linked to a 15% mortality rate among people living with HIV and low CD4 counts.

An international network of clinicians have discovered a severe, necrotizing form of mpox with a high mortality rate in people living with HIV (PLWH) and immunosuppression, according to research published in The Lancet.

The global case series, which is the first major study of mpox among people living with advanced HIV, showed a mortality rate of 15% in individuals with HIV and low CD4 counts below 200 cells per mm³.

“Our findings are particularly pertinent for countries with low levels of HIV diagnosis or without universal free access to antiretroviral therapy and intensive care units, where the interaction of uncontrolled HIV infection and mpox is more prevalent,” the authors wrote. “In these countries, a concerted effort to provide urgent access to mpox antivirals and vaccines is of critical importance.”

To come to these findings, the authors analyzed data on confirmed mpox—previously referred to as monkeypox—cases among PLWH from between May 11, 2022, and January 18, 2023, provided by clinicians from 19 countries. Contributing centers also completed anonymous structured case report sheets to include variables of interest relevant to PLWH and to capture more severe outcomes.

The data included 382 cases of mpox: 367 cisgender men, 4 cisgender women, 10 transgender women, and 1 nonbinary individual. The median (IQR) age was 35 (30-43) years and all included PLWH were adults with a CD4 cell count of less than 350 cells per mm³ or—in settings where CD4 count was not routinely available—stage C HIV.

At the time of mpox diagnosis, 91% of individuals in the study were known to be living with HIV and 8% had a concurrent opportunistic illness. Of those with known HIV, 65% were adherent to antiretroviral therapy.

At the time of the study publication, 60 people had died of mpox, with 27 of those individuals included in this study. The researchers noted that all 27 of these individuals had CD4 counts of less than 200 cells per mm³. Overall, among PLWH with this low CD4 count, more deaths occurred in individuals with high HIV viral load.

Of the 382 cases, 243 (64%) had fever and 364 (95%) had a skin rash. Skin rash was initially vesiculopustular in 297 (78%) PLWH and progressed to ulcerative in 84 (22%) individuals. Additionally, the median (IQR) number of skin lesions was 15 (8-35), and median duration to resolution was 23 (18-33) days.

Despite these comparatively low medians, there were 36 individuals with 100 or more skin lesions and 43 with a duration to resolution of 40 days or more. Among this group, most had CD4 cell counts of less than 200 cells per mm³ and detectable HIV plasma viral loads.

Regarding type of lesion, 235 (62%) PLWH had genital lesions, 203 (53%) had anal lesions, 144 (38%) had oral involvement, and 20 (5%) had ocular involvement.

The most common presentation among the study group was having multiple, large, rounded ulcers with necrotic centers and raised borders.

Organ complications were also recorded among the study population, with dermatological, respiratory, and secondary bacterial infection complications being the most common. Additionally, 10 individuals developed ecchymotic or hemorrhagic lesions and 84 developed necrotizing lesions, of which 55 were coalescing.

Severe complications were more common in PLWH with a CD4 cell count of less than 100 cells per mm³ compared with more than 300 cells per mm³—these included necrotizing skin lesions (54% vs 7%), lung involvement (29% vs 0%) that occasionally included nodules, and secondary infections and sepsis (44% vs 9%).

“Physicians caring for people with mpox and advanced HIV disease must be made aware of the severe outcomes and high mortality that can occur, especially when cutaneous and bloodstream bacterial superinfection sets in,” the authors wrote.

“Clinical trials tailored to this group are needed to evaluate the effect of antiviral agents and preventive vaccines to modify disease outcomes,” they continued. “In the absence of these data, people with HIV and low CD4 cell counts who need to be hospitalized with mpox should be considered for expanded access to these therapies where available and specific guidelines with best practices should be developed.”


Mitjà O, Alemany A, Marks M, et al. Mpox in people with advanced HIV infection: a global case series. Lancet. Published online February 21, 2023. doi:10.1016/ S0140-6736(23)00273-8

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