Abstract
Background
Mpox is a viral zoonotic disease that has seen a resurgence in recent years, with outbreaks reaching beyond its traditional endemic zones in Central and West Africa to parts of Europe and North America. The relationship between human immunodeficiency virus (HIV) infection and mpox outcomes, particularly hospitalization rates, remains underexplored despite the known immunosuppressive effects of HIV. This systematic review and meta-analysis aimed to clarify the association between HIV infection and the likelihood of hospitalization in mpox cases.
Methods
A literature search was conducted through PubMed, Embase, Web of Science, Scopus, and the Cochrane Library up until August 10, 2024. The eligibility criteria focused on observational studies that evaluated hospitalization rates among mpox cases, distinguishing between HIV-positive and HIV-negative individuals. Newcastle-Ottawa Scale was used for evaluating study quality. The meta-analysis used a random-effects model to accommodate expected study heterogeneity using R software (V. 4.4).
Results
The search yielded 686 records, with 14 studies meeting the inclusion and exclusion criteria after screenings and full-text assessments. The pooled analysis revealed a 56.6% increased risk of hospitalization among HIV-positive mpox cases compared to HIV-negative individuals (95% CI: 18.0–107.7%). Notable heterogeneity (I² = 76%) was observed, likely reflecting variations in study settings and methodologies. Sensitivity analysis confirmed the robustness of these findings, and no significant publication bias was detected (Egger’s test p-value = 0.733).
Conclusion
HIV infection is associated with a statistically significant increased risk of hospitalization in mpox cases. There is a critical need for integrated care and enhanced surveillance, especially in populations with high HIV prevalence. Our findings emphasize the importance of ongoing research to better understand HIV and mpox co-infection and to refine management strategies for this vulnerable group. Future studies should focus on long-term outcomes and the effectiveness of various management strategies across different healthcare settings.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12879-025-10512-6.
Keywords: Mpox, Monkeypox, Human immunodeficiency virus, HIV, Hospitalization, Meta-analysis
Introduction
Mpox, previously known as monkeypox, is a viral zoonotic disease caused by the monkeypox virus, a member of the Orthopoxvirus genus [1]. For the purpose of this study, severe mpox was defined as cases requiring hospitalization due to complications such as pneumonia, sepsis, encephalitis, or the need for intensive care. These complications significantly increase the morbidity associated with mpox and often necessitate advanced medical interventions. Although it was first identified in 1958 among laboratory monkeys, the first human case was recorded in 1970 in the Democratic Republic of Congo [1]. Since then, mpox has become endemic in several Central and West African countries, with sporadic outbreaks occurring in non-endemic regions, particularly in Europe and North America, due to international travel and trade [2]. The recent global resurgence of mpox cases, including significant outbreaks in countries with no previous history of the disease, has raised public health concerns and highlighted the need for a comprehensive understanding of the factors contributing to severe outcomes, including hospitalization and mortality [3–6].
One of the critical areas of investigation is the relationship between mpox and human immunodeficiency virus (HIV) infection [7]. HIV continues to be a significant global health challenge, with approximately 38 million people living with the virus worldwide [8]. HIV compromises the immune system, leading to increased susceptibility to infections and complications from various diseases, including opportunistic infections [9–11]. Given that mpox can cause severe disease in individuals with compromised immunity such as the elderly and those with HIV, it is plausible to hypothesize that HIV-positive individuals might be at higher risk of severe mpox outcomes, including hospitalization [12].
The interaction between HIV and other infectious diseases has been a subject of extensive research. Studies have shown that HIV-positive individuals are more likely to experience severe outcomes when infected with various pathogens, including tuberculosis, hepatitis, and other viral infections [13–15]. The immunosuppression caused by HIV, particularly in individuals with low CD4 cell counts, is a well-known risk factor for increased morbidity and mortality from co-infections [16]. In the context of mpox, there is growing evidence that HIV-positive individuals, especially those with poorly controlled HIV, may experience more severe manifestations of mpox, including higher rates of hospitalization and prolonged recovery times [17].
Mpox typically presents with a prodromal phase characterized by fever, lymphadenopathy, and malaise, followed by a rash that progresses through several stages, including macules, papules, vesicles, pustules, and scabs [17]. While the disease is generally self-limiting, with symptoms resolving within 2–4 weeks, severe cases can occur, particularly in individuals with underlying health conditions or immunocompromised states [18–20]. Complications of mpox can include secondary bacterial infections, respiratory distress, and encephalitis, which may necessitate hospitalization [18]. Understanding the factors that predispose individuals to severe mpox, particularly in the context of HIV co-infection, is crucial for developing targeted prevention and treatment strategies.
Several studies have evaluated the clinical outcomes of mpox in HIV-positive individuals, but the results have been variable. Some studies suggest that HIV-positive individuals [21, 22], particularly those with high viral loads or low CD4 counts, are at increased risk of severe mpox and require hospitalization more frequently than their HIV-negative counterparts. Other studies, however, have not noted any significant association between HIV status and mpox severity, leading to uncertainty about the role of HIV in influencing mpox outcomes [23, 24]. This systematic review and meta-analysis aimed to address these gaps in knowledge by synthesizing the existing literature on the association between HIV infection and hospitalization among mpox cases. Specifically, this study examined whether HIV-positive individuals are at higher risk of hospitalization due to mpox compared to HIV-negative individuals.
Methods
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Table S1) [25]. The aim was to synthesize existing evidence on the association between HIV infection and hospitalization among mpox cases.
Eligibility criteria
For our systematic review and meta-analysis on the association between HIV infection and Mpox outcomes, we defined eligibility criteria using the PICOS framework as follows: Our Population of interest included human subjects diagnosed with Mpox, specifically examining the outcomes between HIV-positive and HIV-negative individuals. There was no specific Intervention studied; instead, our focus was on the natural Comparison of outcomes between the two groups. The primary Outcomes investigated were hospitalization rates due to Mpox, assessing how these were influenced by HIV status. Eligible Study Designs included observational studies such as cohort, case-control, and cross-sectional designs that provided clear stratifications or subgroup analyses based on HIV status. To ensure the relevance and currency of our data, we included studies published in English up to August 10, 2024. Exclusion criteria were applied to remove studies that lacked necessary robustness or relevance, including case reports, case series with fewer than ten participants, reviews, book reviews, conference abstracts, editorials, and studies that did not offer clear stratification based on HIV status or failed to differentiate between HIV-positive and HIV-negative individuals. Additionally, studies focusing exclusively on animal models or non-human subjects were excluded. This structured approach ensured a comprehensive and methodologically sound basis for synthesizing available evidence to understand the impact of HIV on Mpox outcomes. Articles available only in the English language were considered for inclusion.
Search strategy
A comprehensive literature search was conducted using the following electronic databases: PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. The search strategy was designed to capture all relevant studies on the association between HIV and mpox outcomes. The search terms included a combination of Medical Subject Headings (MeSH) and free-text terms related to “monkeypox” or “mpox,” “HIV,” and “hospitalization,”. Boolean operators (AND, OR) were used to combine search terms. The detailed search strategy is depicted in Table S2.
Study selection
All identified records were imported into a semi-automated web based software (Nested-Knowledge). Duplicates were automatically removed by the software. The titles and abstracts of the remaining records were screened independently by two reviewers to identify potentially eligible studies. Full texts of the studies deemed relevant were then retrieved and assessed for eligibility based on the inclusion and exclusion criteria. Any disagreements between the two reviewers were resolved through discussion or consultation with a third reviewer.
Data extraction and quality assessment
A standardized data extraction form was used to collect relevant information from the included studies. We used Nested-knowledge software for data extraction. The extracted data included study characteristics such as author’s name, year of publication, country of study, study design, sample size, and duration of the study. Additionally, data on the number of patients hospitalized in both the HIV-positive (PLHIV) and non-HIV groups were collected, along with effect sizes, including odds ratios or risk ratios and their confidence intervals (CIs) for hospitalization based on HIV status. Two reviewers independently extracted the data, and any discrepancies were resolved by consensus or through consultation with a third reviewer.
The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) [26] for observational studies. This tool evaluates studies based on three broad categories: selection of study groups, comparability of groups, and ascertainment of the outcome of interest. Each study was scored out of a possible nine points, and studies were categorized as low, moderate, or high quality based on their scores. Two reviewers conducted the quality assessment independently, with discrepancies resolved through discussion.
Statistical analysis
A meta-analysis was conducted to quantify the association between HIV infection and the risk of hospitalization among mpox cases. The pooled relative risk (RR) was obtained by combining the number of hospitalized PLHIV and non-HIV mpox cases and their respective total numbers. The pooled estimates, with 95% CIs, were calculated using a random-effects model, given the expected heterogeneity among studies. The random-effects model accounts for variability both within and between studies, providing a more conservative estimate of the effect size. Statistical heterogeneity among studies was assessed using the I² statistic, which describes the percentage of variability in effect estimates that is due to heterogeneity rather than chance. An I² value greater than 50% was considered indicative of substantial heterogeneity. Publication bias was assessed using funnel plots and Egger’s test. Funnel plots visually assess asymmetry in the distribution of study effect sizes, which may suggest publication bias. Egger’s test was used to statistically evaluate the asymmetry of the funnel plot, with a p-value of less than 0.05 indicating significant publication bias. Additionally, the influence of individual studies on the pooled estimates was evaluated by systematically removing one study at a time and recalculating the overall effect size. All statistical analyses were performed using R software version 4.4 [27].
Results
Literature search
The literature search identified a total of 686 records from three major databases: PubMed (373 records), Embase (250 records), and Web of Science (63 records). After removing 172 duplicate records, 514 unique records were screened based on their titles and abstracts. From this screening process, 320 records were excluded, resulting in 194 reports that were sought for full-text retrieval. All 194 reports were successfully retrieved and assessed for eligibility. Of these, 180 full-text articles were excluded for specific reasons: 114 did not report the outcome of interest, 186 were excluded due to the exposure not being of interest, and 66 were considered not relevant to the research question. Finally, 14 studies [18, 21–24, 28–36] met the eligibility criteria and were included in the systematic review and meta-analysis (Fig. 1).
Fig. 1.
PRIMSA flow diagram showing article screening and selection process
Characteristics of included studies
The characteristics of the14 included studies are presented in Table 1. Six studies were conducted in Europe, and captured data predominantly from Western and Central European countries. Three studies originated from the United States. Two studies spanned multiple countries, enhancing the global perspective of the analysis. Additionally, individual studies from Canada, Peru, and Brazil contributed to a broader understanding of the interplay between HIV and mpox in North and South America. The majority of the studies employed retrospective cohort designs, indicating a common approach for analyzing historical data on HIV and mpox. Two cross-sectional studies were included, and one case-control study offered insights by comparing individuals with and without HIV in terms of their hospitalization risks due to mpox. These studies collectively included a range of participant numbers, with the smallest study involving 100 individuals and the largest encompassing 5,391 participants. The quality assessment of the studies is presented in Table S3.
Table 1.
Characteristics of included studies
| Author | Country | Design | total | Age (Mean and SD/Median and IQR) | Male and female | PLHIV | Non-HIV | Hospital in HIV | Hospital in non HIV | OR/RR (95% CI) for hospitalization | Adjusted variables |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hoffmann 2023 (28) | Germany | Retrospective cohort study | 546 | 39 (20–69) | NA | 256 | 58 | 7 | 3 | NA | NA |
| Angelo 2023 (29) | Multiple countries (GeoSentinel network) | Cross-sectional study | 226 | 37 (32–43) | 100% | 92 | 134 | 13 | 17 | NA | NA |
| Olivencia 2024 (30) | European region (> 99%) | Retrospective cohort study | 1472 | 38.6 ± 9.6 | 99% | 719 | 659 | 19 | 39 | NA | NA |
| Ramírez-Soto 2024 (21) | Peru | Retrospective cohort study | 3561 | 32 (27–38) | 96.40% | 2123 | 1438 | 154 | 38 | PLHIV with ART: OR = 2.26 (1.47 to 3.48), PLHIV without ART = 11.2 (6.78 to 18.3) | Age and sex |
| Krug 2024 (31) | France | Retrospective cohort study | 1888 | 36 (30–44) | 98% | 216 | 746 | 6 | 29 | NA | NA |
| Allard 2024 (23) | Canada | Retrospective cohort study | 155 | 37 (27–45) | 95.8% | 106 | 297 | NA | NA | aOR: 0·97 (0·29 − 3·23) | Age and vaccination status |
| Garneau 2023 (24) | USA | Retrospective cohort study | 100 | 35.3 (range: 19-65.6) | 97% | 46 | 54 | 10 | 7 | uOR: 1.8 (0.6–5.2) | NA |
| Martín-Iguacel 2023 (32) | Spain | Retrospective cohort study | 2122 | PLHIV = 36 (30–43), Non-HIV = 40 (34–46) | 97.55% | 842 | 1280 | 22 | 22 | NA | NA |
| Silva 2024 (33) | Brazil | Prospective cohort study | 409 | 33 (28–40) | 91.7% | 213 | 196 | 24 | 19 | NA | NA |
| Schildhauer 2023 (34) | USA | Retrospective cohort study | 4611 | 35 (25–48) | 94.40% | 1878 | 2733 | 140 | 120 | NA | NA |
| Henao-Martínez 2023 (35) | Multiple countries | Retrospective case-control study | 1477 | 35 ± 11.8 | 90% | 487 | 990 | 51 | 38 | NA | NA |
| Philpott 2024 (22) | Georgia | Retrospective cohort study | 1921 | 34 (29–40) | 97.6% | 1124 | 797 | 86 | 37 |
CD4 < 350cells/mm3: Viral load unsuppressed: RR = 3.6 (2.0–6.4),Viral load suppressed: RR = 2.3(1.2–4.4), CD4 > 350cells/mm3: Viral load unsuppressed: RR = 1.5(0.6–3.5),Viral load suppressed: RR = 0.9(0.5–1.5) |
Age, Race, gender |
| Laurenson-Schafer 2023 (18) | WHO Member States | Retrospective analysis of surveillance data | 53,913 | 34 (29–41) | 96·4% | 6296 | 8986 | 369 | 468 | Not immunocompromised: aOR = 0∙91 (0∙71–1∙16), immunocompromised = 2.00 (1.68–2.37) | Age, sex, and HIV and immunocompromised status |
| Chastain 2023 (36) | USA | Retrospective cohort study | 322 | PLHIV = 36.4 (8.69), Non-HIV = 33.7 (12.4) | 90.37% | 93 | 229 | 10 | 9 | NA | NA |
Abbreviations:- aOR: Adjusted Odds Ratio, ART: Antiretroviral Therapy, HIV: Human Immunodeficiency Virus, IQR: Interquartile Range, NA: Not Available or Not Applicable, OR: Odds Ratio, PLHIV: People Living with HIV, RR: Relative risk, SD: Standard Deviation, uOR: Unadjusted Odds Ratio
Risk of bias assessment
The Newcastle-Ottawa Scale (NOS) results for the included studies in our systematic review reveal scores ranging from 6 to 8 out of a possible 9 points, reflecting generally good methodological quality across the board. Most studies scored well in “Study Selection,” “Comparability,” and “Outcome” assessment areas, indicating robust study design and reliable outcome measurement. However, some studies were marked down for not demonstrating that the outcome of interest was not present at the start of the study or due to inadequacies in follow-up. This variation in scores highlights areas where future research could improve, particularly in ensuring longer and more complete follow-up periods to better capture relevant outcomes.
Risk of hospitalization with HIV among mpox cases
The meta-analysis aggregated data from 13 studies to assess the risk of hospitalization among mpox cases in relation to HIV status (Fig. 2). The pooled RR across all included studies was calculated at 1.391 (95% CI: 0.989 to 1.958). This result indicates that while there appears to be a possibility of an increased risk of hospitalization for HIV-positive individuals, the association does not reach statistical significance (p = 0.056). Moreover, the heterogeneity among the studies is substantial, evidenced by an I² value of 81%.
Fig. 2.
Risk of hospitalization among PLHIV mpox cases
Influencer analysis and sensitivity analysis
We conducted an influencer analysis to identify outliers within the meta-analysis. The study by Olivencia et al. was identified as an outlier (Figure S1). Additionally, we performed a leave-one-out sensitivity analysis to assess the impact of individual studies on the overall result. This analysis indicated that the study by Olivencia et al. notably affected the result (Figure S2). Consequently, we re-performed the meta-analysis after omitting the Olivencia et al. study. The revised results from the meta-analysis show a pooled RR of 1.566 (95% CI: 1.180 to 2.077). This indicates a statistically significant increased risk of hospitalization for PLHIV compared to non-HIV individuals (p = 0.005) (Fig. 3). The analysis still shows substantial heterogeneity among the studies, with an I² value of 76%, suggesting significant variability in the effects observed across different studies.
Fig. 3.
Risk of hospitalization among PLHIV mpox cases after omitting outlier study
Publication bias
Funnel plots were used to evaluate publication bias in the meta-analysis, by plotting RRs against their standard errors (Fig. 4). The plot demonstrates a symmetrical distribution around the vertical line representing the pooled risk ratio, suggesting a lack of significant publication bias. This visual assessment corroborated by Egger’s test, which detects funnel plot asymmetry through a regression-based approach, yielding a p-value of 0.733. This result indicates no statistically significant publication bias among the included studies. Together, these combined analyses confirm the robustness of the meta-analysis results, suggesting that the results are unlikely to be influenced by publication bias.
Fig. 4.
Funnel plot assessing publication bias
Discussion
The relationship between HIV infection and the severity of infectious diseases, particularly zoonotic infections like mpox, remains a critical area of research due to the implications for clinical management and public health policy. Our systematic review and meta-analysis aimed to elucidate the association between HIV status and hospitalization rates among individuals diagnosed with mpox. The findings reveal a statistically significant increased risk of hospitalization for PLHIV compared to those without HIV, with a pooled RR of 1.566 (95% CI: 1.180 to 2.077).
The increased risk of hospitalization in HIV-positive individuals could be attributed to several factors inherent to HIV infection, primarily the immune suppression associated with the disease. Our findings align with prior evidence that HIV-positive individuals experience worsened outcomes in infections, likely due to immune compromise [18, 22]. This elevated risk highlights the significant strain on healthcare systems, especially in high HIV prevalence regions. Increased demand for hospital beds, ICUs, and specialized care, along with prolonged stays and higher costs, highlights the need for targeted interventions like vaccination, early diagnosis, and improved access to ART to reduce hospitalizations and alleviate system pressures. Mpox, manifesting with a spectrum of symptoms from mild to severe, can progress to severe forms more quickly in immunocompromised individuals, necessitating hospitalization [18, 22]. The substantial heterogeneity observed in the meta-analysis (I² = 76%) suggests variability in the effect sizes across studies, which could be influenced by differences in study designs, population demographics, local healthcare systems, and methods of clinical management. Such diversity highlights the complex interplay of factors that can influence disease outcomes in different settings.
Our findings are consistent with earlier research indicating that immunocompromised individuals, including those with HIV, are at an increased risk of severe outcomes from viral infections. For instance, studies on influenza and other respiratory illnesses have shown similar trends [37, 38], where HIV-positive status correlates with increased hospitalization rates and complications among patients with other viral illness [22]. However, our analysis also points to an inconsistency in the magnitude of risk across different studies, a factor that is not entirely explained by the current literature, suggesting that local factors and individual patient profiles play significant roles. Moreover, the influence of HIV on the severity of mpox has not been as extensively documented as its impact on other viral diseases, making this analysis an important contribution to the field. The variability and risk associated with HIV and mpox point towards a need for tailored clinical approaches to managing mpox in HIV-infected populations. A previous systematic review found no significant association between hospitalization rates and HIV infection status among mpox cases (OR: 1.13; 95% CI, 0.28 to 4.46; I² = 80%) [39]. Previous meta-analyses have also demonstrated significant differences in the clinical manifestations of mpox between individuals living with HIV and those without. These studies identified a notably higher prevalence of symptoms like skin rash and proctitis in HIV-positive patients, emphasizing the impact of immunocompromise on disease severity. Conversely, outcomes such as cough and diarrhea showed varied significance, highlighting the complex effects of HIV status on mpox symptoms [17]. Their analysis included only a few studies, which may explain the difference in results compared to our study. Our analysis, which incorporates a greater number of studies, offers more robust evidence of a significant association between HIV status and the likelihood of hospitalization in mpox cases. This expanded evidence base reinforces the reliability of our findings.
One of the strengths of this review is its comprehensive and systematic approach to collating existing data from diverse geographical and clinical settings, providing a broad view of the patterns of mpox hospitalization relative to HIV status. Moreover, the use of robust statistical methods to adjust for potential outliers and to assess publication bias lends further credibility to our findings. However, several limitations must be acknowledged. First, the inherent limitations of observational studies included in the meta-analysis, such as potential confounding factors and biases in data collection, could affect the reliability of the findings. The studies included in this meta-analysis did not differentiate between Mpox clades (West African vs. Congo Basin), which may have varying virulence and could influence hospitalization rates. Additionally, the exclusion of non-English language studies might have omitted relevant data that could influence the overall analysis. The substantial heterogeneity noted also indicates that the pooled estimate of risk must be interpreted with caution, as it may not accurately reflect specific subgroups or regions.
The rationale for undertaking this systematic review and meta-analysis on the association between Mpox and HIV is critical due to the increasing global incidence of Mpox and its intensified clinical outcomes in HIV-positive populations. Understanding this association is crucial as HIV compromises the immune system, potentially exacerbating Mpox infection severity, leading to higher rates of complications and hospitalizations. By analyzing combined data from various studies, this SRMA aims to clarify how HIV status affects Mpox outcomes, which is essential for developing targeted clinical protocols and improving health outcomes.Our findings show the importance of vigilant clinical monitoring and potentially pre-emptive hospitalization strategies for mpox in HIV-positive patients, particularly those with poor viral control or low CD4 counts. Healthcare providers should be aware of the increased risk and possibly adjust treatment protocols to include more aggressive symptom management and monitoring in this population. From a public health perspective, this study highlights the need for targeted health communications and interventions to prevent and manage mpox outbreaks, especially in populations with a high prevalence of HIV. Public health policies could also benefit from incorporating considerations for immunocompromised individuals in their infectious disease outbreak preparedness plans.
Further research is necessary to determine the specific mechanisms through which HIV exacerbates mpox severity and to determine the roles of ART adherence, CD4 counts, and viral load in modifying these outcomes. Longitudinal studies could provide further insights into the trajectory of mpox in HIV-infected individuals over time. Additionally, studies in non-English speaking regions and those incorporating qualitative data could enrich the understanding and management strategies of mpox in diverse settings.
Conclusion
Our analysis confirms that HIV infection is linked to an increased risk of hospitalization in mpox cases. This association highlights the need for integrated care approaches and improved surveillance to manage mpox effectively in populations with HIV-prevalence. The findings emphasize the need for ongoing research into the interaction between HIV and mpox in order to enhance public health responses and improve patient outcomes during future outbreaks.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
The authors acknowledge the Nested-Knowledge, MN, USA for providing the access to the software.
Author contributions
Muhammed Shabil - Led the study, wrote the initial draft, and secured funding. Shilpa Gaidhane and Renu Sah - Assisted with concept and oversight. Roopashree R, Anoop Dev, and Rukshar Syed - Handled data analysis and software tools. Mandeep Kaur, Manish Srivastava, G. V. Siva Prasad, Pranchal Rajput, Ambanna Yappalparvi, and Harish Kumar - Contributed to data collection and manuscript editing. Amit Barwal, Danish Kundra, Ganesh Bushi, and Prakasini Satapathy - Involved in methodological design and review. Quazi Syed Zahiruddin - Provided project supervision and editorial input.
Funding
No funding was received for this study.
Data availability
The data is with the authors and available on request.
Declarations
Ethics approval and consent to participate
Not applicable.
Competing interests
The authors declare no competing interests.
Clinical trial number
Not applicable.
Consent for publication
Not applicable.
Consent to participate
Not applicable since this is a review and not involved any human.
Ethical considerations
Not applicable.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Muhammed Shabil and Shilpa Gaidhane contributed equally as first authors.
Contributor Information
Quazi Syed Zahiruddin, Email: zahirquazi@dmiher.edu.in.
Renu Sah, Email: renusahdoc@gmail.com.
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Data Availability Statement
The data is with the authors and available on request.