Research | Open Access | Volume 9 (2): Article 100 | Published: 17 Jun 2026
Menu, Tables and Figures
Eric Nzirakaindi Ikoona1,&, Lucy Namulemo2, Mary Magdalene Sinnah1, Mohamed Alex Vandi1, Foday Sahr1
1National Public Health Agency, Freetown, Sierra Leone, 2Lindsey Wilson University, School of Professional Counselling, Columbia, Kentucky, USA
&Corresponding author: Eric Nzirakaindi Ikoona, National Public Health Agency, Freetown, Sierra Leone. Email: ikoonae@yahoo.com, ORCID: https://orcid.org/0000-0003-3402-1961
Received: 03 Mar 2026, Accepted: 16 Jun 2026, Published: 17 Jun 2026
Domain: Infectious Disease Epidemiology
Keywords: Mpox, HIV, viral suppression, MVA-BN vaccination, Sierra Leone
©Eric Nzirakaindi Ikoona et al. Journal of Interventional Epidemiology and Public Health (ISSN: 2664-2824). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article: Eric Nzirakaindi Ikoona et al., Fourfold or higher mpox mortality in people living with HIV: A national cohort from Sierra Leone’s 2025 outbreak. Journal of Interventional Epidemiology and Public Health. 2026; 9(2):100. https://doi.org/10.37432/jieph-d-26-00070
Introduction: People living with HIV (PLHIV) with immune compromise may face a higher risk of severe mpox, but African outbreak data remain limited.
Methods: We conducted a retrospective national cohort study of laboratory-confirmed mpox cases in Sierra Leone from 9 January to 26 November 2025. Surveillance records were linked to HIV programme registers in DHIS2. Mpox-attributable death was the primary outcome. Logistic regression estimated adjusted odds ratios (aOR) adjusted for age, sex, and district. Among PLHIV, mortality was stratified by viral suppression (<1,000 copies/mL) and CD4 count (<200 vs ≥200 cells/µL) using Fisher’s exact test.
Results: Of 5,442 confirmed cases, 4,891 (89.9%) had documented HIV status; 426 (8.7%) were PLHIV. Mortality was higher in PLHIV than in HIV-negative individuals (15/426, 3.5% vs 38/4,465, 0.9%; aOR 3.72; 95% CI: 1.98-6.99; p<0.001). Among 312 PLHIV with viral-load data, mortality was 13.8% (9/65) in unsuppressed PLHIV and 0.8% (2/247) in virally suppressed PLHIV (OR: 19.7; p<0.001). Among 286 PLHIV with CD4 data, mortality was 15.4% (8/52) with CD4 <200 cells/µL and 1.3% (3/234) with CD4 ≥200 cells/µL (OR: 14.0; p<0.001). In seven districts, ART-clinic vaccination coverage reached 71.0% within six weeks.
Conclusion: Excess mpox mortality in PLHIV was concentrated in those with unsuppressed viral load (OR 19.7) or CD4 <200 cells/µL (OR 14.0), while virally suppressed PLHIV had mortality similar to HIV-negative individuals. Findings support using HIV treatment and immune status to prioritise risk assessment, monitoring, and vaccination through ART clinics.
Mpox (formerly monkeypox) has emerged as a significant public health threat in Africa and globally, with outbreaks increasing in frequency and geographic scope since 2022 [1]. On 13 August 2024, the Africa Centres for Disease Control and Prevention (Africa CDC) declared mpox a Public Health Emergency of Continental Security (PHECS) under Article 3 of its statutes. This was the first such declaration by the agency since its establishment. It mandated coordinated continental action to contain the outbreak and mitigate cross-border transmission [2]. The following day, the World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern (PHEIC) for the second time [3,4]. Together, these two declarations activated a co-led Africa CDC/WHO Incident Management Support Team and a Continental Preparedness and Response Plan with an initial six-month budget of approximately US$600 million (excluding vaccine costs) across affected Member States [5]. The first global mpox outbreak analysis further demonstrated sustained international transmission across previously unaffected settings [6], underscoring the urgent need to understand risk factors for severe disease and mortality, particularly among vulnerable populations.
People living with HIV (PLHIV) represent a population of particular concern during mpox outbreaks. Immunological studies indicate that effective orthopoxvirus control requires robust cell-mediated immunity, including both CD4+ and CD8+ T-cell responses [7,8]. PLHIV with unsuppressed viral loads experience progressive CD4+ T-cell depletion and immune dysregulation, which may compromise control of orthopoxvirus replication. Data from the global 2022-2023 clade IIb outbreak demonstrate that PLHIV with advanced immunosuppression (CD4 count <200 cells/µL) experience more severe clinical presentations and substantially higher mortality than HIV-negative individuals [9-11].
However, African clinical data concerning clade II mpox and HIV have remained limited relative to the longer literature on clade I MPXV in the Democratic Republic of the Congo and Central Africa. Published African clade II clinical data were for many years drawn largely from the 2017-2018 Nigerian outbreak [12,13]. Subsequent evidence from Nigeria’s 2022 clade IIb outbreak has characterised HIV-associated risk factors, clinical predictors of poor mpox outcomes, and the disproportionate burden among people with advanced HIV disease [14,15], complemented by the global SHARE-NET case series demonstrating case-fatality exceeding 15% among PLHIV with CD4 counts below 100 cells/µL and below 3% among those with CD4 counts ≥500 cells/µL [11]. Most other published evidence on HIV-mpox interactions originates from European and North American cohorts during the 2022-2023 clade IIb outbreak, when surveillance reports showed that most reported cases occurred in the WHO European Region and the Region of the Americas [9,10,16]. These cohorts differ from many African populations of PLHIV in HIV-1 subtype distribution, antiretroviral therapy (ART) coverage, viral suppression rates, and overall health-service access [17-21].
Sierra Leone experienced its largest recorded mpox outbreak in 2025 amid sustained global mpox transmission [1,6]. By 26 November 2025, surveillance recorded 5,442 laboratory-confirmed cases and 60 deaths [22]. The outbreak occurred in a context where adult HIV prevalence is 1.4% (ages 15-49), with an estimated 77,000 PLHIV (2022) [19]. Sierra Leone received 220,500 doses of the MVA-BN vaccine between February and December 2025, with first doses arriving on 26 February 2025 and vaccination commencing on 27 March 2025; as of 4 December 2025, a cumulative 186,053 individuals had been vaccinated nationally [22,23]. WHO recommends use of mpox vaccines during mpox outbreaks, including for children and adolescents where indicated [3]. In Sierra Leone, the national emergency-use and campaign protocol set eligibility at adults and adolescents aged 12 years and above at identified risk of exposure, including PLHIV, close contacts of confirmed cases, healthcare workers in mpox treatment centres, and other key populations. This lower age limit was also consistent with WHO prequalification of MVA-BN for adolescents aged 12-17 years [22,24]. In Sierra Leone, AIDSInfo 2023 estimates indicate that 76% of PLHIV know their status and 99% of those who know their status receive ART [19].
The outbreak presented an opportunity to evaluate integrated service delivery platforms. When MVA-BN vaccines became available in mid-2025, the Ministry of Health introduced clinic-based vaccination through ART platforms in selected districts alongside conventional fixed-site and outreach delivery in others. This study had three objectives: first, to quantify the association between HIV status, viral suppression, CD4 count, and mpox mortality during Sierra Leone’s 2025 outbreak; second, to evaluate vaccination coverage achieved through the integrated HIV platform approach; and third, to derive preparedness recommendations for future outbreaks in high-HIV-burden settings.
Study design and setting
We conducted a retrospective national cohort study of all laboratory-confirmed mpox cases reported in Sierra Leone from 9 January through 26 November 2025, in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidance [25]. All confirmed cases, whether PLHIV or HIV-negative, were followed to the mortality endpoint; HIV-negative cases served as the internal comparison group for the HIV-associated mortality analysis. Sierra Leone is a West African nation of approximately 8.4 million people organised into 16 administrative districts. The National Public Health Agency (NPHA) coordinates disease surveillance, outbreak response, and epidemic preparedness activities nationwide.
Data sources and linkage
Case data were extracted from the national mpox surveillance database maintained within the DHIS2 platform. Confirmed cases were defined as individuals with a compatible clinical presentation and positive polymerase chain reaction (PCR) testing for orthopoxvirus at the NPHA reference laboratory or a designated regional laboratory.
HIV status was ascertained through linkage with national HIV programme registers, also maintained within DHIS2. Linkage was performed using the unique national health identification number assigned to individuals accessing HIV services. For cases without direct identifier matches, probabilistic linkage using name, date of birth, sex, and facility of diagnosis was performed with manual verification by trained data clerks. Documented HIV status was ascertained for 4,891 of 5,442 cases (89.9%): 3,963 (72.8% of all cases) through direct DHIS2 identifier matching and 928 (17.1%) through probabilistic matching with manual verification. The remaining 551 cases (10.1%) could not be classified by either method and were recorded as having unknown HIV status.
For mpox cases identified as PLHIV through linkage, we extracted additional data from the HIV programme registers: the most recent viral-load result within 12 months prior to mpox diagnosis, the most recent CD4 count within 12 months prior to mpox diagnosis, current ART regimen, ART enrolment date, and current treatment status. Among PLHIV with viral-load data, 64.1% of measurements were performed within 6 months of mpox diagnosis and 35.9% between 6 and 12 months; for CD4 measurements, 58.4% were within 6 months and 41.6% within 6-12 months. Viral suppression was defined as a viral load <1,000 copies/mL, consistent with WHO guidance [26]. Advanced immunosuppression was defined as a CD4 count <200 cells/µL, consistent with WHO consolidated HIV guidelines [27].
Outcomes
The primary outcome was mpox-attributable death, defined as death occurring during confirmed mpox illness or within 30 days of diagnosis in the absence of a documented alternative cause. We acknowledge that this operational definition is more conservative than the WHO interim surveillance definition [28], which additionally includes deaths in which mpox was a contributing factor.
The secondary outcome was mpox vaccination coverage among PLHIV in districts implementing ART-clinic-based vaccination. Vaccination coverage was calculated as the proportion of eligible individuals aged at least 12 years enrolled in ART programmes who received at least one dose of the third-generation non-replicating MVA-BN vaccine [3] during the study period. Children younger than 12 years were not eligible for vaccination under the Sierra Leone campaign and were therefore excluded from the vaccination-coverage denominator; ART-clinic child denominators and deaths in this ineligible age group require separate extraction and will be incorporated in the companion vaccine-effectiveness study. This study measured vaccination coverage and post-vaccination cases; it was not designed to assess vaccine effectiveness or vaccine safety.
Statistical analysis
Descriptive statistics characterised the study population. Continuous variables were summarised as medians with interquartile ranges (IQR) and compared using Wilcoxon rank-sum tests; categorical variables were summarised as frequencies and percentages and compared using chi-square or Fisher’s exact tests as appropriate.
The primary analysis compared mortality between PLHIV and HIV-negative individuals using multivariable logistic regression, estimating adjusted odds ratios (aOR) with 95% CI. Models were adjusted for age (continuous), sex (male/female), and district of residence (16 categories) as potential confounders.
Among PLHIV with available immunological data, we stratified mortality by (i) viral suppression status and (ii) CD4 category, comparing proportions using Fisher’s exact test given anticipated small cell sizes. Coverage estimates were reported with 95% CI using the Wilson score method. All analyses were conducted using Stata version 17 (StataCorp, College Station, TX, USA). A two-sided p-value <0.05 was considered statistically significant.
Ethical considerations
This study was conducted as part of public health emergency response activities under the authority of Sierra Leone’s NPHA. The Sierra Leone Ethics and Scientific Review Committee determined that the study constituted routine surveillance and outbreak response and was therefore exempt from individual informed-consent requirements. All data were analysed in de-identified form.
Socio-demographic and clinical characteristics
During the study period, 5,442 laboratory-confirmed mpox cases were reported across all 16 districts of Sierra Leone (Table 1). The median age was 28 years (IQR: 22-36), with the majority of cases (68.4%) occurring among adults aged 15-34 years. A total of 386 cases (7.1%) were aged under 15 years, and 1,334 cases (24.5%) were aged 35 years and over. Males comprised 58.0% of cases (n=3,156). The most affected districts were Western Area Urban (n=1,847; 33.9%), Bo (n=612; 11.2%), and Kenema (n=498; 9.1%), collectively accounting for over half of all cases.
The most common clinical presentations included generalised rash (89.2%), fever (76.8%), lymphadenopathy (72.4%), and headache (58.3%). Genital or perianal lesions were documented in 34.6% of cases. The median time from symptom onset to diagnosis was 5 days (IQR: 3-8). Overall, 1,247 cases (22.9%) required hospitalisation, and 60 deaths occurred, yielding an overall case fatality ratio (CFR) of 1.1%.
Comparing PLHIV (n=426) to HIV-negative individuals (n=4,465), PLHIV were older (median 34 vs 27 years; p<0.001) and more likely to be female (52.1% vs 40.8%; p<0.001). PLHIV had higher rates of hospitalisation (38.5% vs 21.2%; p<0.001) and a longer median time from symptom onset to diagnosis (7 vs 5 days; p<0.001). Clinical presentations were broadly similar between groups, though PLHIV more frequently presented with extensive rash involving more than 100 lesions (28.4% vs 12.1%; p<0.001).
Characteristics of cases with unknown HIV status
Of 5,442 confirmed cases, 4,891 (89.9%) had documented HIV status through successful linkage with HIV programme registers; 551 (10.1%) could not be classified by either direct-identifier or probabilistic matching and were recorded as having unknown HIV status. The 551 unknown-status cases were broadly comparable to the 4,891 with documented status in age distribution (median 29 vs 28 years; p=0.42) and sex (male 57.2% vs 58.0%; p=0.71), but were disproportionately drawn from facilities with lower DHIS2 integration maturity and from the earliest outbreak phase before the linkage protocol was fully operational. Seven of the 60 deaths occurred among cases with unknown HIV status.
HIV-related characteristics among PLHIV
Among the 426 PLHIV with mpox, 389 (91.3%) were currently receiving ART, with a median duration on treatment of 4.2 years (IQR: 1.8-7.6). The most common ART regimen was tenofovir/lamivudine/dolutegravir (TLD), used by 312 (80.2%) of those on treatment (Table 2). Viral-load data within the preceding 12 months were available for 312 of 426 PLHIV (73.2%); of these, 247 (79.2%) were virally suppressed, and 65 (20.8%) were unsuppressed. CD4 count data within the preceding 12 months were available for 286 PLHIV (67.1%); the median CD4 count was 418 cells/µL (IQR: 248-612). Of those with CD4 data, 52 (18.2%) had advanced immunosuppression (CD4 <200 cells/µL) and 234 (81.8%) had CD4 ≥200 cells/µL.
HIV status and mortality
Mortality differed substantially by HIV status (Table 3). Among PLHIV, 15 of 426 (3.5%) died, compared with 38 of 4,465 (0.9%) among HIV-negative individuals. After adjustment for age, sex, and district, HIV infection was associated with significantly higher odds of death (aOR: 3.72; 95% CI: 1.98-6.99; p<0.001). The sensitivity analysis restricted to direct-identifier-linked cases yielded a consistent estimate (aOR: 3.64; 95% CI: 1.87-7.07; Supplementary Table S1).
Viral suppression and mortality among PLHIV
Viral suppression was strongly associated with survival (Table 3). Among unsuppressed PLHIV, 9 of 65 (13.8%) died, compared with 2 of 247 (0.8%) among those with viral suppression (unadjusted OR: 19.7; 95% CI: 4.2-93.3; Fisher’s exact p<0.001). The mortality observed among virally suppressed PLHIV (0.8%) was comparable to that observed among HIV-negative individuals (0.9%). Four additional deaths occurred among the 114 PLHIV lacking viral-load data.
CD4 count and mortality among PLHIV
A CD4-stratified mortality analysis was conducted in parallel with the viral-suppression analysis to provide a direct immunological characterisation of mortality risk (Table 3). Among the 286 PLHIV with CD4 data, mortality differed markedly by CD4 category: 8 of 52 PLHIV with CD4 <200 cells/µL died (15.4%), compared with 3 of 234 PLHIV with CD4 ≥200 cells/µL (1.3%) (unadjusted OR: 14.0; 95% CI: 3.5-55.3; Fisher’s exact p<0.001). Mortality among PLHIV with CD4 ≥200 cells/µL approximated that observed among HIV-negative cases (0.9%), whereas advanced immunosuppression was associated with substantially elevated mortality. Four additional deaths occurred among the 140 PLHIV lacking CD4 data.
Vaccination coverage through integrated HIV platforms
Seven of 16 districts implemented integrated mpox vaccination through ART-clinic platforms beginning in June 2025. In these districts, 18,092 eligible individuals aged at least 12 years were enrolled in ART programmes at the time of vaccine deployment. Within six weeks of implementation, 12,847 (71.0%; 95% CI: 70.3-71.7%) had received at least one dose of MVA-BN vaccine. Within the seven integrated-delivery districts, 84.2% of doses were delivered through the ART-clinic channel; the remaining 15.8% were delivered through fixed-site or outreach modalities running concurrently to reach key populations outside the ART cohort.
District-level coverage varied substantially (Table 4), ranging from 27.3% in Tonkolili to 78.9% in Western Area Urban. Tonkolili recorded lower coverage because logistical delays restricted ART-clinic vaccination during the six-week campaign. After excluding Tonkolili, coverage in the other integrated-delivery districts ranged from 64.2% to 78.9%. Urban districts with larger, more concentrated ART-clinic networks achieved higher coverage than rural districts. Among paediatric and adolescent ART enrollees aged 12-17 years (the youngest group eligible under the Sierra Leone campaign), 58.7% were vaccinated within the six-week window. Vaccination refusal rates in ART clinics during the campaign averaged 2.8% based on facility-level monitoring.
The remaining nine districts implemented vaccination through fixed-site mass campaigns at district hospitals and urban health centres, supplemented by facility-based contact-tracing outreach. The nine non-integrated districts collectively had 9,347 individuals on ART at the start of the campaign. Because coverage in those districts was calculated against an estimated at-risk target population rather than an ART-enrolled denominator, direct head-to-head coverage comparison across implementation models is not possible with the available data.
Breakthrough mpox cases in vaccinees
Preliminary per-individual linkage identified three post-vaccination mpox cases that were diagnosed ≥14 days after a first MVA-BN dose (approximately 0.24 per 1,000 vaccinees); none was fatal. The final breakthrough count awaits completion of the planned per-individual vaccination-case linkage, which will form the basis of a companion vaccine-effectiveness analysis.
This national cohort study from Sierra Leone’s 2025 mpox outbreak demonstrates four principal findings. First, HIV infection was associated with nearly fourfold higher mpox mortality than HIV-negative status. Second, this excess risk was concentrated among PLHIV with unsuppressed viral load or CD4 counts below 200 cells/µL. Third, CD4 count and viral suppression yielded concordant mortality patterns, consistent with impaired cell-mediated immunity as a contributor to severe mpox in PLHIV; immune-response serology was not assessed, so we cannot infer a direct causal immune mechanism. Fourth, existing HIV programme infrastructure enabled rapid achievement of high vaccination coverage among PLHIV after MVA-BN became available in 2025.
The magnitude of the HIV-mortality association observed in our study (aOR 3.72) aligns with findings from the 2022-2023 clade IIb outbreak. Multi-country cohorts reported elevated hospitalisation and mortality in PLHIV with advanced immunosuppression, particularly among those with low CD4 counts [9-11]. Our findings extend this evidence to an African outbreak setting. They show that viral suppression and CD4 preservation, rather than HIV serostatus alone, are key determinants of mpox survival. The concordance between viral-load and CD4-stratified mortality analyses provides internal triangulation and supports the interpretation that cell-mediated immune compromise contributes to poor mpox outcomes.
The protective effect of viral suppression and preserved CD4 count is biologically plausible. Effective ART restores immune function, including CD4+ T-cell recovery, which is essential for controlling orthopoxvirus infection [7,8]. Our observation that virally suppressed PLHIV and those with CD4 ≥200 cells/µL experienced mortality equivalent to HIV-negative individuals suggests that the HIV-associated mortality risk is largely modifiable through sustained viral suppression and immune reconstitution.
The socio-demographic profile of our cohort reflects the broader epidemiology of the clade IIb outbreak. The predominance of cases among young adults aged 15-34 years is consistent with patterns reported in multi-country mpox cohorts [9] and aligns with reports from Nigeria’s 2022 outbreak where adults of similar age were disproportionately affected [14,15]. The higher proportion of females among PLHIV in our cohort reflects the underlying HIV epidemiology in western and central Africa [20].
The high vaccination coverage achieved through HIV platforms (71.0% within six weeks) demonstrates the feasibility of leveraging existing health infrastructure for outbreak response. ART clinics offer several advantages as vaccination delivery platforms: established patient relationships facilitating trust and uptake; existing appointment systems enabling efficient scheduling; cold-chain infrastructure for vaccine storage; and healthcare workers experienced in managing PLHIV. Systematic-review evidence supports a substantial protective effect of MVA-BN against mpox, with a pooled single-dose effectiveness of 76% (95% CI: 64-88%) against mpox [29]. The preliminary identification of three non-fatal cases of mpox post-vaccination among more than 12,000 vaccinees is directionally consistent with external evidence of MVA-BN protection, but the present study was not designed to estimate vaccine effectiveness or safety.
Sierra Leone used a single-dose MVA-BN regimen under constrained supply [22,23], per the WHO emergency-use recommendations [30]; the licensed schedule is two doses 4 weeks apart [3]. Phase II data suggest that PLHIV, particularly with prior AIDS, may have blunted immunogenicity after a single dose and may require additional dosing for durable protection [31,32]. Evidence from an LC16m8 open-label randomised trial in people with well-controlled HIV found immunogenicity and no significant safety concerns, but no breakthrough cases in either trial arm precluded vaccine-effectiveness estimation [33]. These data underscore the need for planned second-dose catch-up for the ART-enrolled cohort and operational research into optimal dosing strategies for PLHIV with advanced HIV disease.
Vaccine effectiveness estimation was not feasible because most vaccinations occurred late, the campaign targeted all ART enrollees, precluding within-district unvaccinated comparators, and the small number of breakthrough cases limits statistical power. Vaccine-impact modelling is planned as a companion analysis.
Our results have implications for epidemic preparedness beyond mpox. Countries with a high HIV burden have invested substantially in HIV programme infrastructure over the past two decades [34]. Drawing on our experience, we propose three preparedness recommendations: (i) programmatic pre-linkage of HIV and surveillance data systems within DHIS2 as routine practice; (ii) inclusion of a structured HIV-status field in all outbreak case-investigation forms and vaccination registers from day one of any emergency response; and (iii) establishment of standing memoranda of understanding between the HIV programme, surveillance programme, STI services, and national public-health institute specifying data-sharing rules and analytic responsibilities for outbreak linkage analyses. In the context of ongoing mpox transmission [1,6], sustained integration of HIV/STI and mpox prevention and control programmes is critical to reducing disproportionate burden in Africa and persistent global risk [35].
Limitations
Several limitations warrant consideration. First, the retrospective design and reliance on routine surveillance data may introduce misclassification bias. Viral-load and CD4 measurements performed up to 12 months prior to mpox diagnosis may misclassify current immune status; this misclassification most plausibly biases the mortality contrast towards the null.
Second, our operational definition of mpox-attributable death is more conservative than the WHO interim surveillance definition [28], which also includes deaths in which mpox was a contributing factor. This may underestimate the true mpox-attributable CFR.
Third, routine surveillance did not capture systematic screening for concurrent opportunistic infections (tuberculosis, cryptococcal meningitis, histoplasmosis, and severe bacterial infections), which are important contributors to mortality in advanced HIV disease and may have contributed independently. Mpox patients were managed in designated isolation facilities without routine on-site diagnostics, including cryptococcal antigen, urinary lipoarabinomannan, and GeneXpert MTB/RIF, and non-routine investigations were not captured in DHIS2.
Fourth, 17.1% of HIV-status classifications were achieved through probabilistic matching rather than direct identifier linkage; although manual verification by trained data clerks reduced false-match risk, residual linkage error may contribute to exposure misclassification.
Fifth, this study did not identify the factors underlying mpox deaths among HIV-negative individuals, who accounted for 38 cases versus 15 among PLHIV; these merit dedicated investigation and underscore that assessment of severe-disease risk must extend beyond HIV status alone.
Despite these limitations, the consistency of findings across viral-suppression and CD4-stratified analyses, the concordance with prior African [12-15] and global [9-11] evidence, and the biological plausibility of the immune-status-mortality association support our central conclusions.
Mpox mortality was higher among PLHIV overall, but excess mortality was concentrated among those with unsuppressed viral load or advanced immunosuppression. Among PLHIV, odds of death were higher with unsuppressed viral load (OR: 19.7) and CD4 <200 cells/µL (OR 14.0), while viral suppression and CD4 preservation reduced mortality to the level observed among HIV-negative cases. Risk assessment should therefore include HIV testing when status is unknown, assessment of viral suppression and CD4 count, and review of treatment adequacy. High vaccination coverage achieved through existing HIV platforms demonstrates that ART clinics can serve as effective outbreak-response infrastructure. In the context of ongoing mpox transmission, continued integration of HIV/STI and mpox prevention and control programmes is critical to reducing disproportionate burden in Africa and persistent global risk [35].
What is already known about the topic
What this study adds
This study was conducted using routine surveillance data collected as part of Sierra Leone’s national mpox outbreak response. No external funding was received for this analysis.
Data availability
The datasets analysed during the current study contain sensitive health information and are not publicly available to protect patient confidentiality. Aggregated data may be available from the corresponding author upon reasonable request and with approval from Sierra Leone’s NPHA.
List of abbreviations
aOR: adjusted odds ratio
ART: antiretroviral therapy
CD4: cluster of differentiation 4 (T-helper cell)
CFR: case fatality ratio; CI: confidence interval; DHIS2: District Health Information Software 2
IQR: interquartile range; MVA-BN: modified vaccinia Ankara-Bavarian Nordic
NPHA: National Public Health Agency
PLHIV: people living with HIV
STROBE: Strengthening the Reporting of Observational Studies in Epidemiology
We thank the healthcare workers across Sierra Leone who contributed to mpox case detection, management, and vaccination; the district health management teams for their dedication to outbreak response activities; and the laboratory staff at the NPHA reference laboratory and regional laboratories for their work in case confirmation.
Eric Nzirakaindi Ikoona conceptualised the study, led the analysis, and drafted the manuscript. Lucy Namulemo contributed to the analysis and guided data collection and linkage. Mary Magdalene Sinnah coordinated data collection and linkage. Mohamed Alex Vandi provided technical oversight of laboratory confirmation and surveillance systems. Foday Sahr provided overall leadership of the outbreak response and critically reviewed the manuscript. All authors read and approved the final manuscript.
Supplementary File
| Characteristic | All cases (n=5,442) | All known HIV status (n=4,891) | PLHIV (n=426) | HIV-negative (n=4,465) |
|---|---|---|---|---|
| Age, median years (IQR) | 28 (22-36) | 28 (22–36) | 34 (27-42) | 27 (21-34) |
| Aged <15 years, n (%) | 386 (7.1) | 347 (7.1) | 0 (0.0) | 347 (7.8) |
| Aged 15-34 years, n (%) | 3,722 (68.4) | 3,345 (68.4) | 220 (51.6) | 3,125 (70.0) |
| Aged >34 years, n (%) | 1,334 (24.5) | 1,199 (24.5) | 206 (48.4) | 993 (22.2) |
| Male sex, n (%) | 3,156 (58.0) | 2,848 (58.2) | 204 (47.9) | 2,644 (59.2) |
| Hospitalised, n (%) | 1,247 (22.9) | 1,110 (22.7) | 164 (38.5) | 946 (21.2) |
| Time onset-to-diagnosis, median days (IQR) | 5 (3-8) | 5 (3–8) | 7 (4-11) | 5 (3-7) |
| >100 lesions at presentation, n (%) | 761 (14.0) | 661 (13.5) | 121 (28.4) | 540 (12.1) |
| Deaths, n (%) | 60 (1.1) | 53 (1.1) | 15 (3.5) | 38 (0.9) |
| Note: IQR, interquartile range; PLHIV, people living with HIV. The known HIV-status column, PLHIV column, and HIV-negative column exclude 551 cases with unknown HIV status. Differences between PLHIV and HIV-negative groups were significant (p<0.001) for all characteristics shown. | ||||
| Characteristic | Value |
|---|---|
| Currently receiving ART, n (%) | 389 (91.3) |
| ART duration, median years (IQR) | 4.2 (1.8-7.6) |
| TLD regimen among those on ART, n (%) | 312 (80.2) |
| Other ART regimens, n (%) | 77 (19.8) |
| Viral-load data available within 12 months, n (%) | 312 (73.2) |
| Virally suppressed (<1,000 copies/mL), n (%) | 247 (79.2) |
| Unsuppressed, n (%) | 65 (20.8) |
| CD4 data available within 12 months, n (%) | 286 (67.1) |
| CD4 median cells/µL (IQR) | 418 (248-612) |
| CD4 <200 cells/µL, n (%) | 52 (18.2) |
| CD4 ≥200 cells/µL, n (%) | 234 (81.8) |
| Note: ART, antiretroviral therapy; CD4, cluster of differentiation 4 T-helper cell count; IQR, interquartile range; PLHIV, people living with HIV; TLD, tenofovir/lamivudine/dolutegravir. | |
| Stratum | n at risk | Deaths | CFR (%) | p-value |
|---|---|---|---|---|
| HIV-negative | 4,465 | 38 | 0.9 | Reference |
| PLHIV | 426 | 15 | 3.5 | <0.001* |
| Virally suppressed PLHIV | 247 | 2 | 0.8 | Reference |
| Unsuppressed PLHIV | 65 | 9 | 13.8 | <0.001† |
| PLHIV with CD4 ≥200 cells/µL | 234 | 3 | 1.3 | Reference |
| PLHIV with CD4 <200 cells/µL | 52 | 8 | 15.4 | <0.001† |
| Note: CD4, cluster of differentiation 4; CFR, case fatality ratio; CI, confidence interval; OR, odds ratio; PLHIV, people living with HIV. *Adjusted odds ratio 3.72 (95% CI: 1.98–6.99; p<0.001) from multivariable logistic regression adjusted for age, sex, and district. †Fisher’s exact test; unadjusted OR: 19.7 (95% CI: 4.2–93.3) for unsuppressed versus virally suppressed PLHIV and unadjusted OR: 14.0 (95% CI: 3.5–55.3) for CD4 <200 versus CD4 ≥200 cells/µL. | ||||
| District | Eligible ART enrollees aged ≥12 years (n) | Vaccinated ≥1 dose (n) | Coverage (%, 95% CI) |
|---|---|---|---|
| Western Area Urban | 6,432 | 5,073 | 78.9 (77.9-79.9) |
| Western Area Rural | 2,814 | 2,104 | 74.8 (73.1-76.4) |
| Bo | 2,987 | 2,123 | 71.1 (69.5-72.7) |
| Kenema | 2,143 | 1,467 | 68.5 (66.5-70.5) |
| Bombali | 1,456 | 967 | 66.4 (63.9-68.8) |
| Kailahun | 1,342 | 862 | 64.2 (61.6-66.8) |
| Tonkolili | 918 | 251 | 27.3 (24.5-30.3) |
| All 7 districts | 18,092 | 12,847 | 71.0 (70.3-71.7) |
| Note: ART, antiretroviral therapy; CI, confidence interval; PLHIV, people living with HIV. Vaccination coverage was calculated as the number of eligible ART enrollees aged ≥ 12 years who received at least one MVA-BN dose within six weeks of ART-clinic deployment. | |||