Who got vaccinated for mpox? A cross-sectional survey on behavioral correlates of vaccine uptake among men who have sex with men attending an STI/HIV reference center in Rome, Italy

Abstract

Background

Following the 2022 outbreak, vaccination against mpox became available in many European countries using a third-generation non-replicating smallpox vaccine (MVA-BN). It is primarily recommended for individuals at higher risk of exposure, including men who have sex with men (MSM), especially those reporting multiple partners, group sex, chemsex, or recent sexually transmitted infections (STIs).

Methods

A cross-sectional survey about mpox vaccination uptake was conducted between October 2023 and October 2025 among MSM attendees of an STI/HIV center (Rome, Italy). An anonymous questionnaire, self-administered online, investigated demographic data, sexual behaviors, STI history, and drug use for sex. Univariable and multivariable logistic regression models were used to identify factors associated with self-reported mpox vaccination.

Results

Of the 331 MSM who completed the questionnaire, 85 (25.7%) reported having received mpox vaccination, whereas 17 had already been vaccinated against smallpox (5.1%). Four participants reported having acquired mpox infection (1.2%). In univariable analyses, mpox vaccination was associated with history of STI, higher number of sexual partners, group sex, use of dating apps, HIV PrEP, use of erectile dysfunction agents (EDA), sexualised drug use (SDU), and chemsex. In multivariable analysis, uptake of mpox vaccination remained independently and positively associated with EDA (aOR: 1.88, 95% CI: 1.02-3.48, p=0.044), HIV PrEP (aOR: 3.32, 95% CI: 1.62-6.81, p<0.001) and chemsex (aOR: 2.44, 95% CI: 1.22-4.90, p=0.012), whereas it showed an inverse association with reporting female partners in the previous year (aOR: 0.25, 95% CI: 0.07-0.89, p=0.033).

Conclusions

Among MSM participants in our survey, mpox vaccination uptake was reported by only about one quarter of the individuals. Uptake was independently and positively associated with both chemsex and HIV-PrEP use, with HIV-PrEP showing the strongest association. Overall uptake remains suboptimal, highlighting persistent gaps in mpox vaccination coverage among individuals at higher risk. This underscores the need to reinforce integrated combination-prevention pathways in HIV/STI services, also in the context of HIV PrEP continuum.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12879-026-13966-4.

Introduction

Mpox (formerly known as monkeypox) is a zoonotic orthopoxvirus infection, caused by MPXV, historically endemic in parts of Central and West Africa.[1] Since May 2022, however, it has caused an unprecedented multi‑country outbreak with sustained human‑to‑human transmission outside endemic areas. From May 2022 and as of May 2026, a total of 26,730 cases were reported in the European Union and European Economic Area (EU/EEA) region.[2] In the last year (May 2025 to April 2026), 2,257 cases were reported (458 clade I, 921 clade II and 878 clade unknown), the majority of which in men who have sex with men (MSM) for both clades (> 90%) [2]. Over the same period, the hospitalization rate was 13.1% for clade I and 7.7% for clade II, with only one death reported in a person infected with clade II. In Italy, over 1,000 cases have been reported since the beginning of the outbreak, and 199 cases have been reported in May 2025-April 2026 (43 clade I, 3 clade II and 153 clade unknown).[3] A substantial variability across the different Italian regions has been observed, with the Lazio region almost consistently ranking among the first three regions with the highest number of cases.

Cutaneous manifestations represent the hallmark of mpox infection, with other common symptoms being fever, sore throat, headache, and swollen lymph nodes.[4] Nonetheless, the 2022–2024 global outbreak was characterized by novel or atypical dermatological patterns, with mild or even absent systemic symptoms.[4] Localized mucocutaneous lesions, most likely at the virus inoculation site, could be restricted to the ano-genital region, particularly when MSM were affected.[4–7] In this context, close physical contact during sexual activity became the main mode of transmission, with cases frequently linked to multiple partners, group sex, and attendance of sex‑on‑premises venues and mass gatherings.[8] The 2022 outbreak also highlighted the intersection between mpox vulnerability and established Sexually Transmitted Infection (STI)/HIV risk environments, including possible common drivers such as sexualized drug use (SDU) and chemsex, which can increase partner numbers, prolong sexual sessions, and reduce condom negotiation. [9, 10] SDU is defined as the use of a wide range of illicit substances in the context of sexual encounters. They include substances to improve sexual performance, such as Viagra and “poppers”, recreational or party drugs (such as cocaine, ecstasy, amphetamines, and ketamine), as well as drugs specifically associated with “chemsex”, which is in fact an SDU subcategory. [11] The term “chemsex” refers to the voluntary intake of specific drugs (“chems”) to facilitate, enhance and prolong sexual sessions. [12] Despite a certain heterogeneity in the definition of these drugs, a triad of psychoactive substances, i.e., gamma hydroxybutyrate/gamma butyrolactone (GHB/GBL), crystal methamphetamine (crystal meth), and mephedrone, is usually considered as the classical “chems”.

In October 2025, the European Centre for Disease Prevention and Control (ECDC) has called for heightened awareness and targeted prevention measures following the first detections of locally acquired mpox clade Ib cases in four EU/EAA countries, including Italy. [13] The ECDC recommended to make vaccination available to all individuals at substantially higher risk of exposure to MPXV, and to advise individuals at higher risk of infection to seek vaccination proactively. Vaccination represented a central pillar to stop the 2022 outbreak and prevent mpox spread. [14] The most widely used vaccine in Europe and North America is the third‑generation, replication‑deficient Modified Vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN). [15] MVA-BN was developed for smallpox preparedness but provides cross‑protection against other orthopoxviruses, including mpox. [16,17] MVA-BN is administered as a 2-dose subcutaneous injection (separated by at least 28 days). This vaccine is effective in preventing mpox and can reduce the severity of symptoms in infected persons. Although randomized efficacy trials against mpox were not feasible during the outbreak, a rapidly growing body of observational evidence supports substantial real‑world vaccine effectiveness, both in Europe and the U.S.[18, 19] In the U.S. study based on nationwide electronic health records, two doses of MVA-BN were associated with lower odds of mpox compared with unvaccinated controls, and protection appeared stronger after completion of the 2‑dose schedule. [19].

At the beginning of August 2022, Italy launched its vaccination campaign against mpox, when the Italian Ministry of Health issued interim circulars outlining indications and operational aspects of pre‑exposure vaccination in selected high‑risk groups, largely mirroring international risk‑based approaches. [20,21] The first tranche of the MVA-BN vaccine was distributed according to a specific plan that took into account the number of cases reported in the different Italian regions. The Lazio region (where Rome is located) received 1,200 doses, while Lombardy, Emilia-Romagna and Veneto received 2,000, 600 and 400 doses, respectively. [22].

At the population level, the decline of the 2022 Italian epidemic has been attributed to a combination of reactive behavior changes within affected communities (e.g., reduced frequency of sexual encounters and increase in safer sex practices) and targeted control strategies, including contact tracing and vaccine rollout in high‑activity networks. [23] However, incidence started declining before vaccines became widely available, and additional factors likely contributed to controlling the outbreak, such as a reduction in the susceptible population following a high number of infections and risk communication efforts. Still, the reasons underlying the outbreak fadeout are complex and published data in this regard are conflicting. Model data do not support the hypothesis that viral circulation has induced saturation effects in high-risk groups, contributing to the case decline [23], and some studies have found that immunity in the highest risk groups has been the sole responsible for the decline of the epidemics [24,25].

Despite availability and recommendations, vaccine uptake among MSM has been variable and often suboptimal. [26] Access constraints, low risk perception, concerns about adverse events, misconceptions regarding protection from historical smallpox vaccination, and missed opportunities in sexual health services can all shape the uptake. In parallel, engagement in structured prevention pathway, particularly HIV pre‑exposure prophylaxis (PrEP) programs may facilitate vaccination through frequent contact with services, prevention literacy, and provider‑initiated offers of additional interventions. [27, 28] In Italy, PrEP uptake has been historically limited by structural and informational barriers (including limited reimbursement pathways in some regions, uneven service distribution, stigma, and the burden of repeated monitoring), potentially influencing broader uptake of combination prevention tools, though the efforts made in recent years have made it possible to significantly expand the population of MSM in PrEP [29].

Limited data exist regarding behavioral correlates of mpox vaccination uptake among MSM from European countries, particularly from Italy. [28, 30, 31] A systematic review and meta-analysis on the global prevalence and correlates of mpox vaccine acceptance and uptake only included two Italian studies, but none of the two was on MSM. [26] To the best of our knowledge, only one study investigated determinants of vaccine uptake in Italy (specifically in the Lazio region), focusing on early uptake, i.e., within the month following the launch of the vaccination campaign. [32] To help fill this gap of knowledge, we conducted a cross-sectional survey in an STI/HIV reference center in Rome (Italy), to identify behavioral and clinical correlates of mpox vaccination uptake among MSM. Building on our prior surveys exploring doxycycline prophylaxis for STIs, as well as SDU/chemsex and STI vulnerability in the same setting,[33, 34] we specifically examined whether markers of high sexual exposure, SDU/chemsex, STI history and HIV-PrEP use were associated with mpox vaccination uptake in a real‑world clinic population.

Methods

Study setting and design

The study was conducted at the STI/HIV Unit of the San Gallicano Dermatological Institute IRCCS (Rome, Italy). This center is one of the 12 sentinel sites belonging to the Italian STI Surveillance System, and represents the largest center for STI diagnosis and care of central-southern Italy. It also provides HIV counselling and testing and antiretroviral treatment for people living with HIV (PLWH). In this setting, a cross-sectional survey about mpox vaccination was performed between October 2023 and October 2025 using an anonymous self-administered online questionnaire available on a dedicated website (https://pensarapido.ifo.it/). Study participants were recruited among MSM consecutively attending the center for STI/HIV services (counselling/testing, follow‑up visits, or clinical management). Eligible participants were cisgender men aged ≥ 18 years who reported at least one sexual intercourse with another man in their lifetime. Participation in the survey was proposed to Italians; non-Italians were invited to participate only if they were proficient in Italian in order to eliminate potential response errors resulting from linguistic barriers.

The study was conducted in accordance with the Declaration of Helsinki and approved by the Comitato Etico Territoriale Lazio Area 5 (Territorial Ethics Committee Lazio Area 5, Lazio, Italy), protocol code 107/ISG/24, date of approval March, 5 2024). Participant consent was waived by Comitato Etico Territoriale Lazio Area 5 (Territorial Ethics Committee Lazio Area 5, Lazio, Italy) due to the following reasons: (i) data were collected anonymously and (ii) used only in aggregated form.

Data collection

The questionnaire consisted exclusively of obligatory items, which respondents were required to complete in order to proceed. The questionnaire was designed to collect: socio-demographic data (age, marital status, education); relationship characteristics (steady partner for at least 6 months yes/no); sexual behaviors and STI exposure proxies (number of sexual partners in the previous 6 months, group sex in the past year, use of dating apps for sex, condom use, and female sexual partners in the previous year); HIV-related variables (HIV status, PrEP use among HIV‑negative participants); use of substances in sexual contexts, including both broad SDU (“use of drugs for sex”) and specific substances (e.g., crystal methamphetamine, mephedrone, GHB/GBL, poppers, cocaine/crack); use of erectile dysfunction agents (EDA); STI history (lifetime diagnoses of syphilis, gonorrhea, Chlamydia trachomatis and genital warts, any history of STI, and STI in the past year) (see Additional file 1). Data on participation in chemsex events, generally described as chillouts of long duration (24–48 h), involving multiple sexual partners and the availability of stimulant drugs for participants, was also collected. Data on mpox vaccination status, prior smallpox vaccination, and mpox infection were also collected. Results pertaining to chemsex and Doxy-PrEP/PEP from a subset of participants have been reported elsewhere [33,34].

Statistical analysis

The primary outcome was self-reported mpox vaccination (at least one dose: this refers to participants who initiated but did not complete the vaccination schedule together with those who completed the two doses). Descriptive statistics were used to summarize the characteristics of the study participants; continuous variables are reported as medians with interquartile ranges (IQR), and categorical variables as number and percentages. Univariable logistic analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CI) for associations between each covariate and mpox vaccination, adjusted for prior smallpox vaccination to reduce confounding by age related historical vaccination. Participants reporting previous mpox infection were retained in the analyses, as the study aimed to describe behavioral and clinical factors associated with self-reported mpox vaccination, rather than to assess compliance with vaccination eligibility criteria at the time of vaccine rollout. Variables showing evidence of significant association with self-reported mpox vaccination in univariable analyses were considered for inclusion into a multivariable logistic regression model to estimate adjusted odds ratios (aORs). To minimize overlap between closely related categorical variables, potential collinearity was assessed using Cramér’s V test. Where relevant (e.g., HIV-PrEP use), models were additionally adjusted for HIV status (PLWH vs. non‑PLWH). Statistical significance was set at p < 0.05. Analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY, USA).

Results

A total of 331 MSM completed the questionnaire and were thus included in the analyses. No missing data were generated for any of the participants as all questionnaire items were mandatory and the system did not allow respondents to proceed without completing each question. Socio-demographic, behavioral and clinical characteristics of the survey participants stratified according to the self-reported mpox vaccination status are shown in Table 1. They had a median age of 41 years (IQR: 32–50); for the major part they were Italians (95.8%) and were graduated (56.2%). In the majority of the cases, they reported group sex in the past year (74.3%), use of dating apps to seek for sexual partners (77.9%), and inconsistent condom use (90.3%). Around one third of the participants were LWH (32.9%), and approximately one fifth of the 209 MSM not LWH referred PrEP use (19.6%). SDU and chemsex were reported by 25.7% and 15.4% of the study participants, respectively.

Table 1.

Characteristics of the 331 MSM participants, attending an STI/HIV center in Rome, Italy, overall and stratified according to the mpox self-reported vaccination status

Variable	Vaccinated for mpox		Total N = 331
	Yes n = 85	No n = 246
Age (median, IQR)	41 (33–49)	41 (31–50)	41 (32–50)
N. sexual partners (past 6 months) (median, IQR)	3 (2–20)	3 (1–10)	3 (1–11)
	n (%)
Nationality
Italian	82 (96.5)	235 (95.5)	317 (95.8)
non Italian	3 (3.5)	11 (4.5)	14 (4.2)
Education
Graduated	50 (58.8)	136 (55.3)	186 (56.2)
High school or less	35 (41.2)	110 (44.7)	145 (43.8)
Living with HIV (LWH)
No	53 (62.4)	156 (63.4)	209 (63.1)
Yes	29 (34.1)	80 (32.5)	109 (32.9)
Unknown (never tested for HIV)	3 (3.5)	10 (4.1)	13 (4.0)
Married	11 (12.9)	28 (11.4)	39 (11.8)
Steady partner (for at least 6 months)	25 (29.4)	84 (34.1)	109 (32.9)
Group sex (past year)	69 (81.2)	177 (72.0)	246 (74.3)
Use of dating apps	74 (87.1)	184 (74.8)	258 (77.9)
Sexual partners met in
Gay bars	21 (24.7)	78 (31.7)	99 (29.9)
Clubs/discos	30 (35.3)	64 (26.0)	94 (28.4)
Saunas	26 (30.6)	52 (21.1)	78 (23.6)
Cruising areas	26 (30.6)	63 (25.6)	89 (26.9)
Private homes/places	23 (27.1)	55 (22.4)	78 (23.6)
Gyms	5 (5.9)	19 (7.7)	24 (7.3)
Condom use
Yes (always)	9 (10.6)	23 (9.3)	32 (9.7)
No (inconsistent)	76 (89.4)	223 (90.7)	299 (90.3)
Female sexual partner (past year)	3 (3.5)	33 (13.4)	36 (10.9)
HIV-PrEP use a	23 (43.4)	18 (11.5)	41 (19.6)
Any SDU	30 (35.3)	55 (22.4)	85 (25.7)
Chemsex	24 (28.2)	27 (11.0)	51 (15.4)
Lifetime history of STI	79 (92.9)	198 (80.5)	277 (83.7)
STI in the past year	16 (18.8)	41 (16.7)	57 (17.2)
PLWH only	n  = 29	n  = 80	N  = 109
Any SDU	16 (55.2)	16 (20.0)	32 (29.4)
Chemsex	14 (48.3)	13 (16.3)	27 (24.8)
Lifetime history of STI	29 (100.0)	70 (87.5)	99 (90.8)
STI in the past year	7 (24.1)	7 (8.8)	14 (12.8)

^apercentages calculated using only the subset of HIV-negative MSM as the denominator (i.e., 53 vaccinated and 156 non vaccinated, for a total of 209 individuals)

Overall, 85/331 participants (25.7%) reported having received mpox vaccination, while 17/331 (5.1%) reported prior smallpox vaccination. Four participants (1.2%) reported a previous mpox infection, one of them just after the first dose of the mpox vaccine. Vaccination uptake did not differ significantly between Italian and non-Italian participants (25.9% vs. 21.4%, Fisher’s two tailed exact test, p = 1.000).

The univariable associations of socio-demographic variables and sexual behaviors with mpox vaccination are reported in Table 2. Mpox vaccination was generally associated with indicators of higher sexual exposure. Specifically, the odds of vaccination increased with the number of sexual partners in the previous 6 months (for each partner increase, OR: 1.01, 95% CI: 1.00-1.02, p = 0.007). Group sex in the past year (OR: 1.86, 95% CI: 1.01–3.43, p = 0.047), and use of dating apps for seeking sexual partners (OR: 2.23, 95% CI: 1.11–4.49, p = 0.025) were also positively associated with the vaccination status. Conversely, reporting female sexual partners (at least one) in the past year was negatively associated with mpox vaccination (OR: 0.23, 95% CI: 0.07–0.76, p = 0.016). Among HIV‑negative MSM, HIV-PrEP use showed a significant positive association with mpox vaccination (OR: 5.88, 95% CI: 2.83–12.23, p < 0.0001). To assess whether mpox vaccination differed over the study period, we compared vaccination uptake across two recruitment periods: October 2023-September 2024 and October 2024-October 2025. Forty-eight of 168 participants (28.6%) reported mpox vaccination in the first period and 37/163 in the second period (22.7%), with no statistically significant difference between the two rates (p = 0.262). No differences were found by age, marital status, education level, having a steady partner for at least 6 months and condom use. HIV status was not significantly associated with mpox vaccination status. No significant association with mpox vaccination was observed for meeting partners in gay bars (two-tailed Fisher’s exact test, p = 0.272), clubs/discos (p = 0.125), saunas (p = 0.102), cruising areas (p = 0.396), private homes/places (p = 0.378), or gyms (p = 0.808).

Table 2.

Univariable analyses to assess the association of self-reported mpox vaccination, socio-demographic and behavioral factors among MSM attending an STI/HIV center in Rome, Italy

	N. vaccinated (%)	OR (95% CI)	p value
Married
No	74/292 (25.3)
Yes	11/39 (28.2)	1.27 (0.59-2.72)	0.539
Nationality
Italian	82/317 (25.9)
non Italian	3/14 (21.4)	0.78 (0.21–2.87)	0.710
Education
Graduated	50/186 (26.9)
High school or less	35/145 (24.1)	1.17 (0.71–1.93)	0.547
LWH
Noa	53/209 (25.4)
Yes	29/109 (26.6)	1.21 (0.32–4.57)	0.778
Steady partner (for at least 6 months)
No	60/222 (27.0)
Yes	25/109 (22.9)	0.86 (0.50–1.47)	0.573
Group sex (past year)
No	16/85 (18.8)
Yes	69/246 (28.0)	1.86 (1.01–3.43)	0.047
Use of dating apps
No	11/73 (15.1)
Yes	74/258 (28.7)	2.23 (1.11–4.49)	0.025
Condom use
Yes (always)	9/32 (28.1)
No (inconsistent)	76/299 (25.4)	0.87 (0.39–1.96)	0.739
Female sex partner (past year)
No	82/295 (27.8)
Yes	3/36 (8.3)	0.23 (0.07–0.76)	0.016
HIV-PrEP b
No	30/168 (17.9)
Yes	23/41 (56.1)	5.88 (2.83–12.23)	< 0.0001
	Median (IQR)	OR (95% CI)	p value
Age
Vaccinated	41 (33–49)
Non-vaccinated	41 (31–50)	1.02 (0.99–1.04)c	0.139
N. sex partners (past 6 months)
Non-vaccinated	3 (1–10)
Vaccinated	3 (2–20)	1.01 (1.00-1.02)c	0.007

^a13 participants never tested for HIV

^b including only the subset of 209 HIV-negative MSM

^c per 1 unit increase (1 year increase for age; 1 partner increase for N. sex partners)

LWH, Living With HIV; PrEP, Pre-Exposure Prophylaxis

The results of the univariable analyses to assess the associations of mpox vaccination status with SDU and chemsex are reported in Table 3. Vaccination uptake was significantly more frequent among MSM reporting vs. those not reporting use of specific substances in sexual contexts: crystal methamphetamine (63.0% vs. 22.4%), mephedrone (51.6% vs. 23.0%), GHB/GBL (42.9% vs. 22.2%), poppers (36.8% vs. 22.6%), and EDA (41.1% vs. 21.3%). Chemsex showed a strong association with mpox vaccination (OR: 3.21, 95% CI: 1.71–6.02, p < 0.001). PLWH reporting any SDU were almost 5 times more likely to report mpox vaccination (OR: 4.76, 95% CI: 1.89–12.02, p < 0.001).

Table 3.

Univariable analyses to assess the association of self-reported mpox vaccination with SDU, chemsex, and individual drugs among MSM attending an STI/HIV center in Rome, Italy

	N. vaccinated (%)	OR (95% CI)	p value
Any SDU a
No	55/246 (22.4)
Yes	30/85 (35.3)	1.86 (1.08-3.19)	0.025
Any SDUa in PLWH
No	13/77 (16.9)
Yes	16/32 (50.0)	4.76 (1.89–12.02)	< 0.001
Chemsex
No	61/280 (21.6)
Yes	24/51 (47.1)	3.21 (1.71–6.02)	< 0.001
Crystal Methamphetamine
No	68/304 (22.4)
Yes	17/27 (63.0)	6.11 (2.61–14.33)	< 0.001
Mephedrone
No	69/300 (23.0)
Yes	16/31 (51.6)	3.56 (1.65–7.67)	0.001
GHB/GBL
No	61/275 (22.2)
Yes	24/56 (42.9)	2.61 (1.42–4.80)	0.002
Ketamine
No	78/311 (25.1)
Yes	7/20 (35.0)	1.49 (0.57–3.87)	0.412
MDMA/Amphetamine
No	74/302 (24.5)
Yes	11/29 (37.9)	1.85 (0.83–4.13)	0.132
PHP (or synthetic cathinones)
No	80/322 (24.2)
Yes	5/9 (55.6)	3.53 (0.92–13.42)	0.066
Cocaine/Crack
No	65/272 (23.9)
Yes	20/59 (33.9)	1.60 (0.87–2.95)	0.134
Poppers
No	60/263 (22.6)
Yes	25/68 (36.8)	2.09 (1.17–3.75)	0.013
EDA use
No	55/258 (21.3)
Yes	30/73 (41.1)	3.02 (1.71–3.36)	< 0.001
Cannabinoids
No	68/275 (24.7)
Yes	17/56 (30.4)	1.30 (0.69–2.45)	0.424
Synthetic cannabinoids
No	85/328 (25.9)
Yes	0/3 (0.0)	not estimable

^aDrugs included: Crystal Methamphetamine, Mephedrone, GHB/GBL, Ketamine, MDMA, PHP and synthetic cathinones, Cocaine/crack

SDU, Sexualised Drug Use; PLWH, People Living With HIV; GHB, gamma hydroxybutyrate; GBL, gamma butyrolactone; MDMA, 3,4-Methylenedioxymethamphetamine; PHP, α-Pyrrolidinohexiophenone; EDA, Erectile Dysfunction Agents

The univariable associations of STI history and mpox vaccination are reported in Table 4.

Table 4.

Univariable analyses to assess the association of self-reported mpox vaccination with previous STI diagnoses, overall and by individuals STI, among MSM attending an STI/HIV center in Rome, Italy

	N. vaccinated (%)	OR (95% CI)	p value
Lifetime history of STI
No	6/54 (11.1)
Yes	79/277 (28.5)	3.13 (1.28-7.65)	0.012
STI in the past year
No	69/274 (25.2)
Yes	16/57 (28.1)	1.16 (0.61-2.20)	0.650
Lifetime history of STI in PLWH
No	0/10 (0.0)
Yes	29/99 (29.3)	not estimable
Syphilis
No	35/158 (22.2)
Yes	50/173 (28.9)	1.47 (0.89-2.43)	0.136
Gonorrhea
No	53/225 (23.6)
Yes	32/106 (30.2)	1.37 (0.81-2.31)	0.235
Chlamydia trachomatis
No	67/288 (23.3)
Yes	18/43 (41.9)	2.19 (1.13-4.27)	0.021
Genital warts
No	57/241 (23.7)
Yes	28/90 (32.9)	1.38 (0.81-2.37)	0.238

STI, Sexually Transmitted Infections; PLWH, People Living With HIV

Any lifetime STI diagnosis was significantly associated with vaccination status (OR: 3.13, 95% CI: 1.28–7.65, p = 0.012), while any STI diagnosis in the past year was not found to be significantly associated with the outcome of interest. Among the individual STIs, only history of Chlamydia trachomatis infection was associated with mpox vaccination (OR: 2.19, 95% CI: 1.13–4.27 p = 0.021).

Prior to multivariable analysis, potential collinearity between SDU and chemsex was explored. A substantial overlap between these two variables was found (Cramer’s V test 0.789). Therefore, to avoid redundancy in the multivariable model, only chemsex was retained, as it showed the strongest association with mpox vaccination in univariable analysis and was considered the most specific behavioral construct. Multivariable logistic regression results are reported in Fig. 1.

Fig. 1.

Multivariable associations of self-reported mpox vaccination, behavioral and clinical factors among MSM attending an STI/HIV center in Rome, Italy: (a) adjusted OR (aOR) and corresponding 95% Confidence Interval (CI) for the covariates included in the multivariable model; (b) Crude OR (dotted line) and aOR (solid line) for each covariate

PrEP use (aOR: 3.32, 95% CI: 1.62–6.81, p < 0.001), EDA use (aOR: 1.88, 95% CI: 1.02–3.48, p = 0.044), and chemsex (aOR: 2.44, 95% CI: 1.22–4.90, p = 0.012) remained significantly associated with mpox vaccination. Reporting female sexual partners remained inversely associated with mpox vaccination (aOR: 0.25, 95% CI: 0.07–0.89, p = 0.033).

Discussion

Literature data on mpox and mpox vaccination are extensive, but only few studies to date have specifically investigated the association between behavioral factors and mpox vaccine uptake. Following the national recommendations for mpox vaccination in August 2022, all the individuals belonging to the high-risk groups identified by the Italian Ministry of Health and attending our STI/HIV center were referred to an external hospital setting, officially designated as the only vaccination center for mpox in the Lazio region, where Rome is located. [35] In this cross‑sectional study, mpox vaccination uptake was self-reported by approximately one quarter of the MSM respondents. In the Lazio region, it has been reported that approximately 50% of the target population has been vaccinated between 2022 and 2024. [36] Although literature data on the vaccination uptake are quite heterogeneous, since it largely varies by country, population and setting, the available data evidence that mpox vaccine uptake is suboptimal. An Australian prospective study estimated a two-dose coverage of 9.6% among MSM from January 2022 to December 2024, [37] whereas a Spanish cross-sectional survey reported a 38% uptake among GBMSM. [38] As of 28 November 2023, in the USA only 21% of the persons at risk for mpox (i.e., MSM ≥ 16 years of age with an indication to receive HIV-PrEP, plus MSM with HIV ≥ 13 years of age) had been fully vaccinated. [39] The last monthly ECDC report (April 2026) highlights that 22% of the clade I mpox cases (92% of which reported in MSM) and 17% of the clade II mpox cases (91% of which reported in MSM) were vaccinated with two doses [40].

It must be noted that vaccine uptake among our HIV-PrEP users (43.4%) was significantly higher than that reported by non-users (11.5%). The former proportion is in line with other Italian data (48.9%) [27] and a recent meta-analysis, which estimated a pooled coverage of 44.8% among HIV-PrEP users (when including high-quality studies only). [41] The repeated healthcare interactions of these individuals provide systematic opportunities to assess additional prevention needs and to offer integrated interventions, including mpox vaccination, particularly if the same clinic offers HIV-PrEP and vaccination [27,28].

When we analyzed the associations of mpox vaccine uptake with clinical and behavioral factors, we observed that uptake is clustered among MSM reporting higher sexual exposure. In our study participants, univariable analyses showed significant associations of self-reported vaccination and number of partners, group sex, dating app use, HIV-PrEP use, SDU and chemsex. These patterns suggest that, in real‑world clinical settings, vaccination is preferentially reaching MSM more involved in high-risk sexual behavior, thus having the highest predicted mpox exposure. Similar results have been reported in an Australian study, where mpox vaccine uptake in GBMSM was associated with living with HIV, recent STIs, non-relationship sex and group sex [42]. Our findings align with outbreak epidemiology and risk-based vaccination strategies. During the 2022 outbreak, mpox transmission in Europe was concentrated within high‑activity MSM networks, often characterized by multiple partners, group sex, sex‑on‑premises venues, and rapid partner turnover [24,43]. Modeling work from Italy indicates that targeted immunization of the most sexually active MSM could prevent future resurgences, reinforcing the rationale for prioritizing those with higher sexual exposure [23].

Several associations that emerged as significant at univariate analyses did not remain significant in the multivariable model, likely reflecting collinearity and the role of downstream mediators such as chemsex and prevention-service engagement (e.g., PrEP), rather than a lack of biological or behavioral relevance, as already observed and reported [27,28]. Chemsex and HIV-PrEP use appeared central in the profile of vaccinated respondents. Participants reporting chemsex and those using HIV-PrEP had substantially higher odds of being vaccinated, and these associations remained independent after adjustment. Chemsex is commonly associated with prolonged sexual sessions, high partner numbers, condomless sex, group sex, online partner seeking and increased STI risk, and has been increasingly documented in other centers, including ours [44,45]. Given that chemsex was one of the prioritization criteria for mpox vaccination during the outbreak, our findings may reflect, at least in part, the implementation of targeted vaccination policies, rather than heightened risk perception among chemsex practitioners. A second key implication concerns HIV-PrEP. In our study, HIV-PrEP use emerged as the strongest independent correlate of mpox vaccination. HIV-PrEP users typically attend structured follow-up visits every three months for HIV testing, renal monitoring, and comprehensive STI screening. In this regard, PrEP programs appear to function as gateways to facilitate not only HIV prevention but also vaccine uptake and enhanced STI control, often referred to as the “PrEP care continuum”.[46] The continuum of PrEP care, which encompasses nine key benchmarks from the identification of individuals at highest risk of HIV to retention in PrEP, [47] offers multiple strategic points at which prevention can be effectively integrated. Each step of this continuum (initial risk assessment, eligibility evaluation, routine follow‑up, etc.) represents a moment in which individuals interact with healthcare services, creating opportunities to reinforce preventive practices beyond HIV alone. This may include promoting consistent condom use, addressing substance use that may influence sexual risk, and supporting vaccination against preventable infections, including mpox.

In this context, the positive association between mpox vaccination and EDA use is clinically and behaviorally plausible. Recreational EDA use among MSM has been increasingly reported, since EDA sustain long-lasting sexual activity and may help overcome the impotence induced by the simultaneous consumption of other drugs (e.g., cocaine, antidepressants) and alcohol [12,48]. Use of EDA, which may serve as a proxy of increased sexual exposure, has been associated with high risk sexual behaviors, such as group sex, condomless sex and multiple partners, and consequently, it may increase STI risk [49,50]. Although EDA access through internet pharmacies or illicit market is now common, seeking prescriptions for EDA might increase regular and direct contact with healthcare providers or sexual health clinics, facilitating preventive conversations and vaccine recommendations.

HIV infection has important implications in the context of mpox, both in terms of clinical outcomes and prevention strategies. PLWH, particularly those with advanced immunosuppression or uncontrolled viral replication, have been shown to experience more severe clinical manifestations of mpox, including higher rates of hospitalization, prolonged disease course, and increased mortality compared with HIV-negative individuals [51]. This supports the classification of PLWH as a priority group for targeted vaccination strategies. However, in our cohort we did not observe a higher uptake of mpox vaccination among MSM LWH. It must be noted that the proportion of PLWH reporting a prior lifetime history of STIs was remarkably high (90.8%), and all vaccinated PLWH in our study had reported STI history. While this pattern may suggest that prior engagement with sexual health services and previous STI diagnoses could influence vaccine uptake, the available data do not allow us to determine whether these factors, rather than HIV status itself, are the main drivers of vaccine uptake in real-world clinical settings.

Finally, we observed a significantly lower proportion of mpox vaccination among MSM who also reported female sexual partners in the previous year. This may reflect different sexual network structures or lower prioritization according to vaccination criteria, rather than differences in perceived risk. Although heterosexual transmission has been documented, particularly in high-resource settings, mpox during the 2022 outbreak was predominantly framed as affecting gay, bisexual, and other men who have sex with men [3–6]. Individuals who engage in sexual activity with both men and women may not fully identify themselves with the MSM community most prominently associated with mpox risk. This could have influenced how relevant they perceived mpox vaccination, although we cannot draw firm conclusions in this regard since this aspect was not specifically assessed in our study.

It must be underlined that some of the behavioral characteristics that emerged as associated with vaccine uptake in our study are included among the prioritization criteria of the Italian Ministry of Health for the vaccination rollout in MSM, them being recent history (last 3 months) of multiple sexual partners, participation in group sex, participation in sexual encounters in venues/clubs/cruising sites/saunas, recent STIs (at least one episode in the last year) and chemsex [20]. However, these criteria are broad and partly overlapping, and particularly in an STI/HIV clinic population, many attendees were likely to meet at least one criterion for vaccine referral. The higher vaccination uptake we observed among HIV-PrEP users and participants reporting chemsex may thus reflect the implementation of risk-based vaccination strategies and greater contact with prevention services. Nonetheless, it may also indicate greater awareness of exposure risk among some individuals, although perceived risk and motivation were not directly measured. It must be noted that in a previous study conducted in the Lazio region, early access to vaccination (i.e., within 30 days from the start of the vaccination campaign) was associated with being an HIV-PrEP user and reporting SDU/chemsex, in addition to a high perceived risk of mpox infection [32].

This study has several limitations. First, several behavioral and clinical variables included in the analyses overlap with prioritization criteria for mpox vaccination during the outbreak. Therefore, the observed associations may partly reflect public health targeting and provider referral, rather than independent determinants of vaccine uptake. Second, the cross‑sectional design precludes causal inference; associations may reflect reverse causality (e.g., vaccination influencing risk behaviors) or unmeasured confounding. Third, this is a single-center study, and our study findings may not be generalizable to other MSM populations. A selection bias may have occurred since MSM participants were recruited among attendees of an STI/HIV reference center and may thus be more engaged with healthcare services and preventive interventions than MSM in the general population. Consequently, vaccination uptake may have been overestimated compared with the general MSM population in Rome. Four, since all data were self-reported, a recall bias and possible misclassification may have occurred, especially for certain variables. In addition, social desirability bias cannot be excluded, particularly for sensitive behavioral variables such as SDU/chemsex, condom use, number of sexual partners and STI history. The anonymous and self-administered online format of the questionnaire may have mitigated this bias, but some participants may have underreported stigmatized behaviors or over reported behaviors perceived as socially desirable. Finally, the four participants reporting a previous mpox diagnosis were not excluded from the analyses. Although previous infection may have affected vaccination eligibility, access, or individual attitudes toward vaccination, potentially introducing a minor methodological inconsistency, a substantial impact on the overall findings is unlikely given the very small number of such participants.

In conclusion, mpox vaccination uptake among our MSM respondents is relatively low, in line with European and global data. Vaccination is concentrated among those reporting chemsex and among HIV-PrEP users, which emerged as the strongest correlates of vaccine uptake. These findings may reflect, at least in part, the implementation of targeted vaccination policies and the greater visibility of these individuals within sexual health services. Strengthening integrated combination prevention, particularly through HIV-PrEP programs and chemsex‑focused interventions, may improve mpox vaccine coverage and preparedness for future outbreaks of sexually transmitted pathogens.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

MVA-BN

Modified vaccinia ankara-bavarian nordic vaccine

MSM

Men who have sex with men

STI

Sexually transmitted infection

SDU

Sexualized drug use

PrEP

Pre‑exposure prophylaxis

HIV

Human immunodeficiency virus

Mpox

Monkeypox

PLWH

People living with HIV

GHB/GBL

gamma-hydroxybutyrate/gamma-butyrolactone

EDA

Erectile dysfunction agents

CI

Confidence intervals

IQR

Interquartile ranges

OR

Odds ratio

Author contributions

Conceptualization, M.G.D., M.Z. and A.L.; methodology, M.Z., E.G., M.G.D. and A.L.; formal analysis, M.G.D., M.Z. and M.G.; investigation, M.Z., M.G., M.G.D., L.G., C.S., E.G., and F.D.T; resources, L.G., C.S., and F.D.T; data curation, M.Z., M.G., M.G.D. and E.G.; writing—original draft preparation, M.Z. and M.G.D.; writing—review and editing, M.G., L.G., C.S., E.G., F.D.T., and A.L.; supervision, A.L.; project administration, A.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Italian Ministry of Health (Ricerca Corrente 2026).

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethic approval and consent to participate

This study (107/ISG/24, date of approval March 5, 2024) was conducted in accordance with the Declaration of Helsinki and approved by was approved by Comitato Etico Territoriale Lazio Area 5 (Territorial Ethics Committee Lazio Area 5, Lazio, Italy). Comitato Etico Territoriale Lazio Area 5 (Territorial Ethics Committee Lazio Area 5, Lazio, Italy) waived the requirement for obtaining individual informed consent for study participation, as data collection was entirely anonymous and all collected information was intended to be analyzed exclusively in aggregated form.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.