Of the 38 people who have died of mpox (formerly monkeypox) in the United States, most were Black cisgender gay men, and among those with a known HIV status, all had AIDS and only two were on antiretroviral treatment, according to a new analysis by the Centers for Disease Control and Prevention (CDC).

“Equitable and early access to prevention and treatment for both mpox and HIV is critical to reducing mpox-related mortality,” the study authors wrote.

Mpox cases have declined dramatically since the outbreak peaked late last summer, but it remains a risk for people living with HIV, who have accounted for around half of all U.S. cases. HIV-positive people on antiretroviral therapy (ART) with an undetectable viral load and an adequate CD4 T-cell count do not fare worse with mpox than their HIV-negative peers, but it’s a different story for those with advanced immune suppression.

A previous CDC analysis found that more than 80% of people hospitalized with severe mpox in the United States were living with HIV. Most of them were Black men who were not on antiretroviral treatment. An international case series presented at the recent Conference on Retroviruses and Opportunistic Infections and published in The Lancet found that mpox can be much more severe in HIV-positive people with a low CD4 count, leading the study authors to argue that mpox should be classified as an AIDS-defining opportunistic infection (OI). The good news is that no one with well-controlled HIV died, suggesting that antiretrovirals can prevent severe outcomes.

In the latest analysis, Aspen Riser, MPH, of the CDC’s Mpox Emergency Response Team, and collaborators from more than a dozen city and state health departments looked at the epidemiological and clinical features of mpox-associated deaths in the United States from May 10, 2022—at the start of the global outbreak—to March 7, 2023. During this period, the CDC tallied 30,235 confirmed and probable mpox cases. Throughout the outbreak, most people with mpox were gay and bisexual men.

From Riser et al, MMWR, April 14, 2023CDC

During the same period, the CDC received reports of 52 deaths among people with confirmed or probable mpox. Of these, 38 had mpox as a cause or contributing factor, for a rate of 1.3 mpox-associated deaths per 1,000 cases. Three people died of other causes (including one suicide) and 11 deaths were still under investigation.

All but two people who died of mpox were cisgender men; one was a cisgender woman, and one was a transgender woman. The median age was 34 years. Among people with available information, 10 had known sexual contact during the three weeks prior to symptoms—nine of them only with men—while two reported nonsexual close contact (sleeping together and caring for a household member with mpox). Of the 11 individuals with a known housing status, five were experiencing homelessness.

Of note, 87% of the those who died were Black compared with 33% of mpox patients who survived and recovered; the rest were white (8%) or Latino (5%). Neary half (47%) lived in the South. Two thirds of the deaths occurred during October and November 2022, as mpox moved beyond the initial cohort of largely white urban gay men.

One person who died had received at least one dose of the Jynneos mpox vaccine, 13 were unvaccinated and 25 had an unknown vaccination status. It is still unclear how well the vaccine works for people with advanced immune suppression.

Among the 33 people with available information, 31 (94%) were living with HIV, and two were immunocompromised for other reasons. In comparison, just 38% of people who recovered had HIV. Of the 24 HIV-positive people with available measurements, all had a CD4 count below 200—the threshold for an AIDS diagnosis—and all but one fell below 50. The median time from symptom onset to death was 68 days. “The lengthy course of illness experienced by most decedents is likely related to a reduced capacity to respond to infection because of co-occurring immunocompromise,” the study authors wrote.

Disturbingly, only two people who died were on HIV treatment when they were diagnosed with mpox, one of whom had an undetectable viral load. Another 19 started antiretrovirals after their mpox diagnosis, but they did not have time for their CD4 count to recover before they died. In seven cases, ART was delayed or interrupted due to concerns about immune reconstitution inflammatory syndrome (IRIS), or worsening symptoms that can occur when immune function improves.

Among the people with available data about their medical care, all had necrotic or widespread mpox lesions. Most (20 of 23, or 87%) were admitted to an intensive care unit, and 25 of 27 (93%) received medications for mpox. All received tecovirimat (TPOXX); in addition, some also received IV vaccinia immunoglobulin, cidofovir, brincidofovir and/or steroids. However, two people did not receive any mpox treatment, and nearly one quarter had delays of up to seven weeks before starting treatment.

The researchers noted that the racial disparities in mpox-associated deaths parallel racial and ethnic disparities in HIV diagnoses and mortality. “Disparities and barriers are apparent at all levels of HIV care, including recognition of HIV risk, access to testing, and access to and receipt of pre-exposure prophylaxis and ART,” they wrote.

The authors advise that everyone with suspected mpox should be evaluated for immunocompromising conditions, including HIV testing. HIV-positive people diagnosed with mpox who are not on antiretroviral treatment should start as soon as possible, and those who are HIV negative should be assessed for pre-exposure prophylaxis (PrEP). In addition, providers should consider early mpox treatment for highly immunocompromised patients.

“These findings highlight the importance of integrating prevention, testing and treatment for multiple sexually associated infections,” they concluded. “Equitable access to prevention, treatment and engagement and retention in care for both mpox and HIV should be prioritized, particularly among Black men and other persons at risk for sexually associated infections.”

In a letter to The Lancet, CDC experts Jesse O’Shea, MD, John Brooks, MD, and Demetre Daskalakis, MD, MPH (the White House national mpox response deputy coordinator) addressed the emergence of mpox as an HIV-related opportunistic infection.

HIV-associated OIs mainly affect two groups: first, people who are unaware of their HIV status and present for care late in the course of disease with an OI that leads to a diagnosis; and second, those who have been diagnosed with HIV but receive intermittent care, are unable to access ART or have limited adherence. “In the U.S.A. today, every opportunistic infection represents a failure within our nation’s HIV care continuum,” the authors wrote.

“The emergence of mpox as an opportunistic infection highlights the need for continued aggressive, comprehensive strategies for HIV testing, prevention, linkage to care and treatment services to prevent HIV infection or disease progression that will reduce people’s risk for severe mpox and mitigate its impact,” they continued. “Taking these actions, alongside providing ready access to mpox vaccination and to services for sexual health and prevention to networks of people who are at risk for mpox and HIV, can diminish the potential of mpox to present as an HIV-associated opportunistic infection.”

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