Updates on Mpox: Vaccination Efficacy and Spectrum of Disease in People with HIV

Impact of vaccination on incidence and severity of MPOX

Two recent studies from the CDC give insight into the impact of MPOX (formerly called monkeypox) vaccination in preventing infection, and on the severity of symptoms in those who became infected after vaccination.

The first examined the effect of either 1 or 2 doses of MPOX vaccine (JYNNEOS) on incidence in men aged 18-49 in 43 U.S. jurisdictions in July-August 2022 (n=9,300 cases). It found that MPOX incidence was 9.6 times higher in unvaccinated men compared with men who had received 2 doses of JYNNEOS vaccine at least 14 days before symptom onset, and 7.4 times higher in those who had received 1 dose ≥14 days earlier.(1)

The second study evaluated the clinical presentation of MPOX cases in 6,329 unvaccinated persons and in 276 persons in the U.S. (>95% male in both groups) who had received 1 dose of JYNNEOS at least 14 days before symptom onset (data on persons who had received 2 doses of vaccine were not available for analysis). Unvaccinated persons were hospitalized with MPOX significantly more frequently than those that had received 1 dose of vaccine (7.5% vs 2.1% of the groups, respectively). Also, while genital rash and rectal symptoms (including pain, proctitis, and tenesmus) occurred roughly equally in both groups, many other symptoms (including fever, chills, malaise, myalgias, GI symptoms [eg, nausea, vomiting, abdominal pain], and multi-site skin lesions) were significantly more likely to occur in unvaccinated persons.(2) Additionally, this study demonstrated striking racial and ethnic differences in the vaccinated group compared with the unvaccinated group – rates of vaccination were much lower in non-white groups. 

These studies did not examine the effect of HIV status on outcomes. 

Spectrum of MPOX disease in people with low CD4 counts

A recently-published international case series (also presented at CROI 2023) serves as a sobering demonstration that MPOX can cause severe disease in people with HIV (PWH), especially in those with low CD4 counts and in particular those who are not on effective (virally suppressive) ART. This study included 382 adults with HIV and CD4 counts <350 cells/mm(or with CDC stage C disease) who presented with MPOX. The cohort’s median CD4 was 211 cells/mm3, 65% were on ART, and 51% had viral suppression (HIV RNA <50 copies/mL). Only 5% of the population had received MPOX vaccination in 2022 (no information is given on whether this represents receipt of 1 or 2 doses of vaccine).  

Authors describe a wide spectrum of MPOX disease, and varied complications, including large necrotizing lesions (often causing functional impairment), pulmonary disease (eg, respiratory symptoms and pulmonary nodules), bacterial superinfections, and sepsis. They found that 28% of the overall cohort was hospitalized, and mortality in this hospitalized group was very high (25%). Authors also identify an IRIS-like phenomenon in people who started or restarted ART during MPOX infection, with a mortality rate of 57% in this group. 16% of the cohort received treatment with tecovirimat, and 2% received other antiviral treatments.

Severe manifestations of MPOX were more likely in persons with very low CD4 counts and with high HIV RNA levels. For example, in those with CD4 counts <100 cells/mmcompared with those with CD4 300-350 cells/mm3, necrotizing skin lesions were seen in 54% vs 7%, lung involvement occurred in 29% vs 0%, and sepsis occurred in 44 vs 9%. All deaths were in people with CD4 counts <200 cells/mm3, and the great majority were in those who also had high HIV viral loads.    

Clinical Bottom Line:

Consistent with other data, these two CDC studies show that JYNNEOS MPOX vaccine greatly decreases the likelihood of infection with MPOX (especially after 2 doses) and that, for those who are infected with MPOX after vaccination, even 1 dose of vaccine greatly decreases the severity of disease. The case series starkly describes the severe MPOX symptoms that may occur in PWH, and their association with low CD4 counts and high HIV RNA levels. Though the incidence of MPOX infections in the US has greatly declined since the 2ndhalf of 2022, the possibility of future outbreaks remains. Together, these studies serve as a reminder to make vaccination available to all who are at risk of exposure to MPOX (and with attention to reducing disparities in access to and uptake of the vaccine), while the case series also suggests the impact of ongoing effective HIV treatment -- ART and viral suppression -- in attenuating the severity of MPOX infection.

The CDC recommends MPOX vaccination comprising 2 doses of the JYNNEOUS vaccine for all who may be at risk for exposure to MPOX; receipt of both doses offers the best protection against MPOX. 


  1. Payne AB, Ray LC, Cole MM, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons - 43 U.S. Jurisdictions, July 31-October 1, 2022. MMWR Morb Mortal Wkly Rep. 2022 Dec 9;71(49):1560-1564. doi: 10.15585/mmwr.mm7149a5.
  2. Farrar JL, Lewis NM, Houck K, et al. Demographic and Clinical Characteristics of Mpox in Persons Who Had Previously Received 1 Dose of JYNNEOS Vaccine and in Unvaccinated Persons - 29 U.S. Jurisdictions, May 22-September 3, 2022.  MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1610-1615. doi: 10.15585/mmwr.mm715152a2.
  3. Oriol Mitjà O, Alemany A, Marks M, et al. Mpox in people with advanced HIV infection: a global case series. The Lancet Published online February 21, 2023. DOI:10.1016/S0140-6736(23)00273-8.
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