Exploring mpox vaccination uptake and tolerability among people living with HIV: A study in an infectious disease unit in Italy

Abstract

Background

A live attenuated non-replicating vaccine (MVA-BN) is approved for immunization against mpox. We provide an overview of the uptake and tolerability of mpox vaccination among people living with HIV (PLWH) in a single centre in Italy and draw comparisons to individuals without HIV.

Methods

We retrospectively collected clinical data of people vaccinated with MVA-BN in a tertiary-level hospital in Florence, Italy. Baseline data were collected from pre-vaccination screening questionnaires; adverse events data were collected before the second dose through another dedicated questionnaire.

Results

We vaccinated 332 subjects. Of them, 36.1% (n = 120) were PLWH, with higher median age, higher rate of previous smallpox vaccination and a higher proportion of transgender individuals compared to people without HIV. As for vaccine tolerability, subcutaneous administration was associated with significantly fewer adverse events than intradermal. There were no significant differences in tolerability between PLWH and individuals without HIV. Among people who did not complete the vaccine cycle, migrant and sex worker populations were disproportionately represented.

Conclusion

Our experience suggests that mpox vaccination has been accepted and well-tolerated in individuals with and without HIV. More work is needed to conduct immunization campaigns in marginalized populations such as migrants and sex workers.

Keywords

Mpox HIV vaccine Italy tolerability migrant

Introduction

Vaccination is essential for preventing and controlling infectious diseases, serving as a cornerstone of global public health. Special attention is needed for people living with HIV (PLWH), who are more vulnerable to infections due to immune system impairment, prompting research into vaccine immunogenicity and safety in this group.

Mpox is a zoonotic disease caused by monkeypox virus (MPXV), an animal Orthopoxvirus endemic to various African Countries. MPXV is classified into two clades: clade I, predominant in Central Africa, and clade II, endemic in West Africa. In July 2022, after a rapid increase in mpox clade IIb cases in non-endemic countries outside Africa, the World Health Organization (WHO) declared it a Global Public Health Emergency. This large and partly ongoing outbreak has caused over 100 000 cases across all WHO regions as of December 31, 2024.¹ The recent mpox outbreak, unlike previous epidemics in the endemic areas, predominantly spread through networks of men who have sex with men (MSM), with transmission mainly occurring via direct contact with infected lesions during sexual encounters.² PLWH were disproportionately affected, comprising 38%–57% of cases globally.³ Severe disease and mortality were strongly linked to low CD4 cell counts.⁴ As an example of this trend, among fatal cases reported in the US until March 2023, 94% were immunocompromised because of HIV infection with low CD4 cell counts.⁵

The MVA-BN vaccine, a live, non-replicating smallpox vaccine by Bavarian Nordic, was EMA-approved for mpox prevention, particularly for MSM, PLWH, sex workers, and healthcare workers. Based on already available data the vaccine was considered safe for immunocompromised individuals, regardless of CD4 count.⁶ A single dose has initially been recommended for people previously vaccinated against smallpox; however, even in this latter population subsequent data showed that two doses led to better protection, particularly in PLWH, leading to recent modifications of recommendations.⁷ Initially administered subcutaneously, intradermal administration, which had been previously found to be presumably noninferior in terms of immunogenicity, was later adopted due to vaccine shortages.⁸

Real-world data demonstrated 75%–90% efficacy for full vaccination and 60%–75% for partial vaccination across various populations, with similar outcomes between subcutaneous and intradermal routes.^9–11 However, immunocompromised individuals showed slightly lower efficacy rates—70% for full and 55% for partial vaccination.^12,13

Not much is known about duration of protection, but available evidence indicates that antibody responses induced by vaccination wane considerably 6–12 months post-vaccination.¹⁴ Based on these findings, some studies have begun advocating for new vaccine platforms and/or the opportunity of a third booster dose in patients at risk.

Notably, during the campaign data have also been collected about factors influencing vaccination uptake and intention to be vaccinated in various populations.¹⁵ Vaccine uptake has been generally high among at-risk populations, with risk awareness as a key driver, especially among PLWH.^16,17 Understanding factors influencing uptake and tolerability differences compared to HIV-negative individuals remains crucial to optimizing vaccination strategies for this vulnerable group.

This study focuses on mpox vaccine uptake and tolerability among PLWH in an Italian center, comparing intradermal and subcutaneous administration with HIV-negative individuals.

Materials and methods

Between September 15, 2022, and May 15, 2024, we retrospectively collected routine data on individuals vaccinated intradermally and subcutaneously with the MVA-BN vaccine at the Infectious and Tropical Diseases outpatient service of Careggi Teaching Hospital (Azienda Ospedaliero-Universitaria Careggi, AOUC) in Florence, Italy. The service regularly monitors around 1600 PLWH and approximately 100 individuals on pre-exposure prophylaxis (PrEP).

Until January 2024, vaccines were administered intradermally as part of an internationally approved vial-sparing strategy, after which regulatory changes mandated a shift to subcutaneous administration. Most individuals received a two-dose schedule, except for those with a history of smallpox vaccination, who were given a single dose following Italian Ministry of Health guidelines.⁷

Demographic and clinical data were obtained from standard pre-vaccination questionnaires (Supplemental Material - Figure 1). Adverse events after the first dose were recorded before the second dose using a self-administered questionnaire (Supplemental Material - Figure 2). All participants, including those receiving a single dose, could report side effects at any time via a dedicated email and phone line. If a participant missed an appointment, they were contacted by phone and the appointment was rescheduled. For individuals who could not be successfully contacted, a minimum of three telephone call attempts were made on three separate days for each missed appointment.

PLWH were mainly recruited from those already under care at the AOUC Infectious and Tropical Disease Unit. HIV-negative individuals were recruited through three primary channels: (i) follow-up patients at the STD/PrEP service; (ii) laboratory and healthcare workers; (iii) the general public, via self-application through a dedicated email and phone number. For those not already under STD/PrEP service care, we provided counselling and an HIV Ab/Ag test, leveraging the opportunity to discuss HIV, PrEP, and other STDs, as suggested by previous studies.¹⁸

Vaccination sessions were held twice weekly by appointment. Additionally, two walk-in sessions were conducted in collaboration with CAT – Cooperativa Sociale, a local organization supporting cisgender and transgender sex workers and victims of trafficking through harm reduction initiatives. CAT’s Street Unit, “Vivian Love,” is part of Tuscany’s anti-trafficking network (SATIS) and also manages the InfoTrans helpdesk, which facilitates access to healthcare and counters sexual exploitation.

Population characteristics and differences were analyzed using descriptive statistics. Categorical variables were compared using the chi-square (X²) or Fisher’s exact test, while continuous variables were assessed with the Mann–Whitney test.

Local Ethics Committees (study coordination site protocol number 23013_BIO) approved the study and the data collection.

Results

During the study period, 332 individuals were vaccinated against mpox at our centre; 120 (36.1%) were PLWH. Intradermal administration was used for 208 (62.6%) patients, while the remainder received the vaccine subcutaneously; intradermal administration was significantly more common in PLWH, mainly for chronological reasons related to changing regulation about administration.

Demographic and clinical data of patients stratified by the presence of HIV infection are synthetized in table 1. Patients without HIV were partly recruited through STD/PrEP service (22.6%) or among laboratory/healthcare workers (6.1%), but were mostly patients who were previously unknown to our centre and who applied for vaccination through dedicated contacts (71.2%); PLWH, on the other hand, were recruited almost entirely from patients regularly seen at our HIV service (97.5%), with only 3 PLWH (2.5%) being previously unknown to our centre. Concerning gender, we found a higher prevalence of transgender women in the HIV group (n = 17; 14.2%) compared to the non-HIV group (n = 12; 5.7%. p = .007). Regarding nationality, most of our patients were Italian, followed by Peruvian and Brazilian nationalities, with no difference between the two groups. The HIV group also had a higher median age (43; IQR = 38–52 years) and, consequently, a higher prevalence of individuals already vaccinated with smallpox (31; 25.8% vs 23; 10.9%, respectively; p < .001). The rate of comorbidities was overall low both in people with and without HIV. The proportion of individuals self-identifying as MSM and sex workers was not significantly different in the two populations (87.3% and 6.1% in the non-HIV group vs 85.8% and 14.2% in the HIV group, p = .025). Thanks to the awareness campaign led by CAT, during the walk-in session 30 individuals who were migrants self-identifying as sex workers, most of them previously unknown to our centre, received the vaccine.

Table 1.

Baseline characteristics of a group of people vaccinated for mpox from 15/09/2022 to 15/05/2024 at the outpatient clinic of the Infectious and Tropical Diseases Unit, Careggi Teaching Hospital, Florence, Italy.

	Without HIV (n = 212)	With HIV (n = 120)	p ^a
Gender; N (%)			0.007
• Cisgender male	194 (91.5)	103 (85.8)
• Cisgender female	6 (2.8)	0 (0)
• Transgender female	12 (5.7)	17 (14.2)
Median age in years [IQR]	37 [31–45]	43 [38–52]	<0.001
Risk category; N (%)			0.004
• MSM	185 (87.3)	103 (85.8)
• Sex worker	13 (6.1)	17 (14.2)
• Health care/laboratory worker	13 (6.1)	0 (0)
• Other	1 (0.5)	0 (0)
Site of recruitment; N (%)			<0.001
• HIV clinic	0 (0)	117 (97.5)
• STD/PrEP clinics	48 (22.6)	0 (0)
• Healthcare/laboratory worker	13 (6.1)	0 (0)
• Community	151 (71.2)	3 (2.5)
Country of origin; N (%)			-
• Italy	186 (87.7)	89 (74.2)
• Peru	12 (5.7)	19 (15.8)
• Brazil	7 (3.3)	2 (1.7)
• Other	7 (3.3)	10 (8.3)
Self-defining MSM	185 (87.3)	103 (85.8)	0.025
Self-defining sex worker	13 (6.1)	17 (14.2)	0.025
N° of expected doses; N (%)			<0.001
• 1 dose	23 (10.9)	31 (25.8)
• 2 doses	189 (89.2)	89 (74.2)
Number of individuals who did not complete the second dose; N (%)	8 (3.7)	10 (8.3)	0.078
Intradermal administration	115 (54.2)	93 (77.5)	<0.001
Adverse event (AE) after the first intradermal dose^b; N (%)			0.164
• Local	31 (32.9)	16 (26.6)
• Systemic	0 (0)	2 (3.3)
Adverse event (AE) after the first subcutaneous dose^b; N (%)			0.698
• Local	11 (12.9)	2 (9.5)
• Systemic	2 (2.3)	0 (0)
Reported any allergies; N (%)			0.299
• None	160 (75.5)	96 (80.0)
• Environmental	36 (17.0)	13 (10.8)
• Pharmacological	16 (7.6)	11 (9.2)
Cardiovascular diseases; N (%)	7 (3.3)	6 (5)	0.443
Asthma; N (%)	7 (3.3)	5 (4.2)	0.691
Other vaccination received between 15 and 30 days before vaccination for mpox; N (%)	13 (6.1)	7 (5.8)	0.912

^bEvaluated only in the person who got two doses (n = 260). Persons with only one dose were excluded.

^aDifferences between the two groups were described using Chi-square test, Fisher’s exact test for categorical variables, and Mann-Whitney test for continuous variables.

Vaccine uptake was generally good, with an about 95% rate of vaccination cycle completion. However, 18 individuals out of 278 (6.5%) did not return for the second dose. The clinical-demographic characteristics of the individuals who did not complete the full vaccination are summed up in Table 2. Ten of them (55.5%) were individuals with HIV and 11 of them (61.1%) were self-identifying as transgender female individuals. HIV infection was not associated with a higher probability of missing the second vaccine dose (p = .123). Among the individuals who missed the second vaccine dose, however, median age was significantly lower (33 [30–41] vs 40 [34–48], p = .008) and being foreign-born was significantly more common (78.9% vs 13.4%, p < .001). Among the 18 individuals who didn’t complete the cycle, most of the HIV-negative ones were in fact transgender women who belonged to a distinct population of South American (Peru) sex workers living in the same community and were recruited through collaboration with CAT. On the other hand, PLWH who didn’t complete the cycle were mostly patients who were routinely followed at our centre and who decided to spontaneously interrupt vaccination, even though advised against this decision. As for vaccine tolerability, adverse events (AEs) after the first dose were generally more common with intradermal administration than with subcutaneous administration (47 (30.1%) versus 13 (12.6%), respectively; p = .002), with no substantial difference between groups: individuals without HIV reported local AEs in 31 (32.9%) cases with intradermal administration and in 11 (12.9%) cases with subcutaneous administration, while PLWH reported local AEs in 16 (26.6%) cases with intradermal administration and in 2 (9.5%) cases with subcutaneous administration. All AEs were mild, with a median duration of 7 days in both groups; we received no reports of AEs via email or phone. Notably, about 20% of the population in both groups had a history of environmental/food or drug allergies; however, unlike other studies, we could not find a significant association between the development of local AEs and the presence of pre-existing allergies. Of note, of the individuals vaccinated and routinely followed up at our centre, only one individual developed mpox: however, his symptoms started approximately 10 days after the first dose, a time window too short to develop vaccine-induced protection against infection.

Table 2.

Baseline characteristics of the group of people (n = 18) who did not complete the entire vaccination cycle with MVA-BN vaccine.

Nationality; N (%)
• Peru	12 (66.6)
• Italy	3 (16.7)
• Brazil	3 (16.7)
Age [IQR]	33 [30–41]
HIV Infection; N (%)	10 (55.5)
Self-defining MSM; N (%)	4 (22.2)
Self-defining sex worker; N (%)	14 (77.7)

Discussion

Our results did not reveal significant differences in mpox vaccine uptake or tolerability between individuals with and without HIV. Overall, vaccine adherence was good, with most participants completing the two-dose schedule. A notable difference between the two groups was the higher likelihood of PLWH receiving a single dose, primarily due to demographic factors and a higher prevalence of previous smallpox vaccination. According to recent evidence and updated guidelines, starting from February 10, 2025, immunocompromised individuals (e.g., people living with HIV or those undergoing immunosuppressive therapy) are recommended to receive a primary vaccination cycle consisting of two doses administered at least 28 days apart, even if they have previously received a smallpox vaccination.⁷

A concerning finding from our study was the incomplete vaccination among a specific marginalized group—migrant transgender sex workers—despite targeted efforts to reach and support them. 11 individuals from this community did not return for their second dose, likely due to the unstable and precarious living conditions many face, which often push personal health to the background.¹⁹ Consequently, since the number of mpox cases and the fear of contracting the infection were decreasing, it’s possible that other priorities might have taken precedence in these individuals’ lives. Lower uptake in vulnerable population is probably also due to lack of institutional prioritization of sex workers, especially female cisgender or transgender sex workers, as an at-risk category for mpox vaccination. Our findings align with recent evidence linking vaccine hesitancy to social determinants such as stigma, low health literacy, and limited access to care.²⁰ Moreover, mpox vaccination acceptance is patterned on definite social gradients, with impoverished people at risk for not completing the vaccine cycle, a factor greatly affecting the equity of vaccines as a public health measure.²¹ To address these gaps, several studies have advocated for more inclusive strategies, such as peer-led education initiatives, mobile clinics, and barrier-free services tailored to vulnerable populations.²² In our small experience, collaboration with local associations like CAT and the establishment of walk-in vaccine sessions have been beneficial strategies in order to reach this particular sex worker community, even if with only partial vaccination. Despite our follow-up efforts—via phone and through our community partners—most individuals who missed the second dose could not be re-engaged. As a result, we have strengthened our collaboration with grassroots groups and are currently supporting the training of peer educators from within the sex worker and migrant communities to promote trust, improve health literacy, and support sustained engagement with vaccination and care services.

Regarding tolerability, the vaccine showed a favourable short-term safety profile, consistent with previous studies reporting mild adverse events (AEs) like redness, itching, and swelling in 31%–80% of cases.²³ Intradermal administration was associated with a higher rate of mild local reactions, especially after the first dose, as reported in other studies.²⁴

However, no significant differences in AE prevalence emerged between individuals with and without HIV, mirroring findings from a large Australian study that observed similar local AE rates in both immunocompromised and general populations.²³ Importantly, no severe or systemic AEs were reported in our cohort, and we did not encounter increased syncopal events, unlike earlier reports.²⁵

While vaccine effectiveness was not a primary objective of this study, we did not observe any mpox cases among the vaccinated individuals under continuous follow-up at our service. This outcome likely reflects both the vaccine’s strong short-term efficacy and the broader epidemiological shift in Italy, where mpox cases have significantly declined since October 2022.

This study has several limitations. As with many retrospective observational studies, the single-centre design and the sample size may limit the generalizability of our findings to other settings or populations. However, the study was conducted at one of the only two centres providing mpox vaccination in the Florence metropolitan area. Additionally, the active collection of AEs data was restricted to individuals who completed the two-dose schedule and only between the first and second dose, potentially underestimating AEs in those who received a single dose or experienced late-onset reactions. Nonetheless, our findings represent one of the first Italian reports comparing mpox vaccine uptake and tolerability between individuals with and without HIV.

In conclusion, our experience suggests that mpox vaccination is well-accepted and tolerated across both groups. PLWH, due to their older median age and higher rate of prior smallpox vaccination, may have been underexposed to the two-dose regimen and could benefit from a booster dose in the event of new outbreaks. Furthermore, our study highlights the persistent disparities in vaccine uptake among marginalized populations, particularly migrants and sex workers. Strengthening partnerships with local grassroots organizations and implementing barrier-free healthcare approaches remain essential strategies for enhancing vaccine coverage and promoting health equity within these vulnerable communities.

Supplemental Material

Supplemental Material - Exploring mpox vaccination uptake and tolerability among people living with HIV: A study in an infectious disease unit in Italy

Supplemental Material for Exploring mpox vaccination uptake and tolerability among people living with HIV: A study in an infectious disease unit in Italy by Samuele Gaggioli, Giuseppe Formica, Valentina Petrini, Alessandra Russo Krauss, Paola Corsi, Alessandro Di Felice, Costanza Fiorelli, Elisabetta Mantengoli, Costanza Malcontenti, Emanuela Francalanci, Giulia Modi, Michele Trotta, Seble Tekle Kiros, Elena Gazzarri, Nicoletta Zocco, Lorenzo Zammarchi, Alessandro Bartoloni and Filippo Lagi in International Journal of STD & AIDS.

Supplemental Material

Supplemental Material - Exploring mpox vaccination uptake and tolerability among people living with HIV: A study in an infectious disease unit in Italy

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical statement

ORCID iDs

Samuele Gaggioli

Filippo Lagi

Data Availability Statement

All clinical and demographic information, including follow-up data, were obtained from electronic health records at the Infectious and Tropical Diseases Unit of Careggi University Hospital (Florence, Italy) and can be accessed upon specific request.*

Supplemental Material

Supplemental Material for this article is available online.

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Supplementary Material

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