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Mpox in people with advanced HIV infection: a global case series
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February 21, 2023 Lancet
Our large case series describes a severe, disseminated form of mpox infection with 15% mortality in individuals with advanced HIV-related disease characterised by CD4 cell counts below 200 cells per mm3. This fulminant form of mpox is characterised by massive necrotising skin, genital and non-genital cutaneous and mucosal lesions (appendix pp 30-52), and is sometimes accompanied by lung involvement with multifocal nodular opacities or respiratory failure and severe cutaneous and bloodstream secondary bacterial infections. The severities of oral and anogenital complications were more marked than previously described.4, 5, 6, 7, 8, 9, 10, 19
As described in the CDC classification, disseminated forms of coccidioidomycosis, histoplasmosis, and mycobacterium avium complex are considered to be AIDS-defining illnesses.20
We describe that people with the lowest CD4 counts (<100 cells per mm3) and highest HIV viral loads (>log4 copies per mL) had disseminated and necrotising forms of mpox, strongly suggesting that this severe form of mpox with systemic involvement could also be an AIDS-defining condition (appendix p 28).20
We describe in detail the clinical course of 27 people with CD4 cell counts of less than 200 cells per mm3 who died,
including ten people who had completed one or two full courses of tecovirimat. We also wish to raise awareness of the 57% mortality rate in those in whom immune reconstitution inflammatory syndrome was suspected following ART initiation or reinitiation.
Among 36 (9%) individuals who had 100 or more lesions and 43 (11%) people who had a duration to resolution of 40 days or more, the majority had CD4 cell counts of less than 200 cells per mm3 and detectable HIV plasma viral loads (appendix pp 15-16).
All complications were more common in people with a CD4 cell count of less than 100 cells per mm3 compared with individuals with more than 300 cells per mm3. Complications included dermatological (49 [58%] of 85 vs 7 [9%] of 75), respiratory (25 [29%] of 85 vs 0 of 75), and bacterial infection (37 [44%] of 85 vs 7 [9%] of 75; figure 2A).

People living with HIV have accounted for 38-50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3).
A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive.
We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30-43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117-291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100-200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance.
A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death.


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