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. 2023 Jan 22;11(2):246. doi: 10.3390/vaccines11020246

Epidemiologic Situation of HIV and Monkeypox Coinfection: A Systematic Review

Brando Ortiz-Saavedra 1,2, Elizbet S Montes-Madariaga 1,2, Cielo Cabanillas-Ramirez 3, Niza Alva 3, Alex Ricardo-Martínez 3, Darwin A León-Figueroa 2,4, Joshuan J Barboza 5, Aroop Mohanty 6, Bijaya Kumar Padhi 7, Ranjit Sah 8,9,*
Editor: Seth Pincus
PMCID: PMC9965118  PMID: 36851124

Abstract

The most recent monkeypox (Mpox) outbreak is mostly affecting men who have sex with men (MSM) who participate in high-risk sexual behaviors, which is typically the case among human immunodeficiency virus (HIV) carriers, according to clinical and epidemiological statistics. The objective of this research is to determine the epidemiological situation of HIV and smallpox co-infection. Until 1 October 2022, a thorough evaluation of the literature was conducted utilizing the databases PubMed, Embase, Scopus, and Web of Science. Studies were evaluated based on the criteria for selection. Fifty-three studies met the selection criteria. A total of 6345 confirmed cases of monkeypox were recorded, and 40.32% (n = 2558) of these cases also had HIV co-infection. In addition, 51.36% (n = 3259) of the men (91.44%; n = 5802), whose ages ranged from 18 to 71 years, exhibited MSM-specific sexual behaviors. Co-infection with these two viruses can be especially dangerous because it can exacerbate the symptoms of both diseases and make them more difficult to treat. People with HIV are more vulnerable to certain infections, including monkeypox, because their immune systems are weakened. Therefore, it is important that they take measures to prevent infection, such as avoiding contact with infected animals, risky behaviors, and maintaining good hygiene.

Keywords: monkeypox, HIV, MSM, co-infection, STIs

1. Introduction

The zoonotic disease known as monkeypox (Mpox) is caused by a double-stranded DNA virus belonging to the genus Orthopoxvirus (monkeypox virus) [1,2]. Humans can contract the Mpox virus through direct contact (sexual or skin-to-skin), respiratory droplets, and fomites that have been exposed to the virus [3].

The World Health Organization (WHO) designated the current outbreak of Mpox disease as a Public Health Problem of International Concern on 23 July 2022 [4]. In addition, 83,487 cases were found in 110 countries by 23 December 2022 [5].

The current global outbreak of Mpox continues to affect mainly homosexuals, bisexuals, and men who have sex with men (MSM), with evidence of an increase in the prevalence of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) [6]. According to WHO, current epidemiological data show that 51% (13,769/26,992) of confirmed cases of Mpox have HIV [7]; this is because HIV, STIs, and Mpox can be transmitted through sexual contact [7,8].

HIV infection and being immunocompromised may or may not affect the presentation of monkeypox [9]. Although it is reasonable to assume that, because of underlying immunosuppression, the course of monkeypox should be more severe in persons living with HIV, the effects of Mpox in this patient population have yet to be determined [10].

Given the prevalence of HIV in Mpox cases during the current outbreak, the present study aimed to assess the epidemiology of HIV and Mpox co-infection.

2. Materials and Methods

2.1. Protocol and Registration

This protocol adheres to the standards specified by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and has been registered in the Prospective International Registry of Systematic Reviews (PROSPERO) database (CRD42022363632) [11].

2.2. Eligibility Criteria

To explore the epidemiological situation of HIV and Mpox co-infection, we included primary research articles that had information on patients older than 18 years with serological diagnosis, polymerase chain reaction (PCR), electron microscopy or immunohistochemical findings positive for Mpox and with a current or previous diagnosis of HIV. We included articles published up to 1 October 2022, with study designs of case reports, case series, and observational studies (cross-sectional, cohort, and case-control). Systematic reviews, scoping reviews, narrative reviews, randomized clinical trials, editorials, conference proceedings, letters to the editor that did not present original results, and other studies that did not answer our research question were excluded. No language restriction was established.

2.3. Information Sources and Search Strategy

A comprehensive search strategy composed of phrases related to “HIV” and “Monkeypox” was used to search Pubmed, Embase, Scopus, and Web of Science (Table 1). Searches were completed on 1 October 2022, and results were evaluated separately by four different investigators.

Table 1.

Search approach for the literature. * NS: Not Specified.

Base Search Strategy
PUBMED #1 “Monkeypox” [MH] OR “Monkeypox” [All Fields] OR “Monkeypox virus” [MH] OR “Monkeypox virus” [All Fields] OR “Monkeypoxvirus*” [TIAB]
#2 “HIV” [MH] OR “HIV” [All Fields] OR “Human Immunodeficiency Virus*” [All Fields] OR “Acquired Immunodeficiency Syndrome” [MH] OR “Acquired Immunodeficiency Syndrome” [All Fields] OR “AIDS*” [All Fields] OR “HIV Infection*” [MH] OR “HIV Infection*” [All Fields] OR “HIV Coinfection*” [All Fields] OR “HIV Long-Term Survivors” [MH] OR “HIV Long-Term Survivor*” [All Fields] OR “Sexually Transmitted Diseases” [MH] OR “Sexually Transmitted Disease*” [All Fields] OR “Venereal Disease*” [All Fields] OR “STD” [TIAB] OR “Sexually Transmitted Infection*” [TIAB] OR “STI” [TIAB] OR “Sexual Behavior” [MH] OR “Sexual Behavior” [All fields] OR “MSM” [All fields] OR “Men Who Have Sex With Men” [All fields]
#3 = #1 AND #2
SCOPUS #1 TITLE-ABS-KEY (“Monkeypox” OR “Monkeypox virus” OR “Monkey Pox” OR “Monkeypoxvirus*”)
#2 TITLE-ABS-KEY (“HIV*” OR “Human Immunodeficiency Virus*” OR “Acquired Immunodeficiency Syndrome” OR “AIDS*” OR “HIV Infection*” OR “HIV Coinfection*” OR “HIV Long-Term Survivor*” OR “Sexually Transmitted Disease*” OR “Venereal Disease*” OR “STD*” OR “Sexually Transmitted Infection*” OR “STI*” OR “Sexual Behavior” OR “MSM” OR “Men Who Have Sex With Men”)
#3 = #1 AND #2
WEB OF SCIENCE #1 ALL = (“Monkeypox” OR “Monkeypox virus” OR “Monkey Pox” OR “Monkeypoxvirus*”)
#2 ALL = (“HIV*” OR “Human Immunodeficiency Virus*” OR “Acquired Immunodeficiency Syndrome” OR “AIDS*” OR “HIV Infection*” OR “HIV Coinfection*” OR “HIV Long-Term Survivor*” OR “Sexually Transmitted Disease*” OR “Venereal Disease*” OR “STD*” OR “Sexually Transmitted Infection*” OR “STI*” OR “Sexual Behavior” OR “MSM” OR “Men Who Have Sex With Men”)
#3 = #1 AND #2
EMBASE #1 ‘monkeypox’/exp OR ‘monkeypox’
#2 ‘human immunodeficiency virus’
#3 = #1 AND #2
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2.4. Study Selection

Using Rayyan QCRI (https://rayyan.qcri.org/, accessed on 7 October 2022), two writers (B.O.S. and E.S.M.M.) independently reviewed the titles and abstracts in accordance with the inclusion and exclusion criteria. The full texts of chosen pertinent studies were searched for an in-depth examination. Conflicts were settled by consensus and, if necessary, input from a third author (D.A.L.F.). Selected articles were stored using the Endnote 20 program.

2.5. Outcomes

Reporting the epidemiological condition of HIV and Mpox co-infection in adult patients was the main result.

2.6. Data Collection Process and Data Items

Three researchers independently retrieved data into an Excel spreadsheet from the chosen objects. The following details were taken out: First author, date of publication, study design, country, N° of patients, sex, age, diagnostic test for Mpox, HIV and Mpox co-infection, other sexually transmitted infections (STIs), Acute HIV, antiretroviral treatment (ART), viral load, CD4+ T-cell count, clinical features, location of skin lesions, treatment and outcomes. To guarantee that there were no duplicate articles or material, a fourth investigator reviewed the final list of included articles.

3. Results

3.1. Study Selection

The search method initially yielded a total of 809 articles. The PRISMA flow chart shows the selection procedure (Figure 1). A total of 437 articles were reviewed after eliminating duplicates (n = 372). Fifty-three articles qualified for inclusion in this systematic review after being chosen from 81 after being screened for titles and abstracts [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64].

Figure 1.

Figure 1

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PRISMA flowchart summarizing the process of choosing the studies.

3.2. Study Characteristics

The studies (n = 53) described cases of concurrent Mpox and HIV infection, including the number of cases, HIV infection, history of sexually transmitted diseases, method of Mpox diagnosis, clinical manifestations, location, and progression of skin lesions, CD4+ T-cell count, HIV viral load, treatment, and outcome (Table 2 and Table 3). Table 2 presents a summary of the general features of the publications included in this review [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]. A total of 6345 confirmed cases of simian pox were reported, distributed across countries: United States (n = 3169) [19,22,28,37,55], Spain (n = 937) [18,25,33,42,49,60], Germany (n = 869) [15,27,30,31,41,43,54], United Kingdom (n = 300) [23,24,29,51,62], France (n = 264) [36], Italy (n = 90) [13,17,34,35,39,40,56,57,58,59], Nigeria (n = 77) [44,45,46], Portugal (n = 71) [12,21,52,53], Israel (n = 26) [63], Belgium (n = 4) [20], Brazil (n = 3) [16,38], Romania (n = 2) [47,48], Czech Republic (n = 2) [14,64], Taiwan (n = 1) [32], Greece (n = 1) [50], and Australia (n = 1) [26] (Table 1). Of the total cases, 40.32% (n = 2558) had co-infection between HIV and Mpox [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64].

Table 2.

Characteristics of included studies.

Author Year Design Country N° of
Participants		 Age Sex (M/F) Diagnostic Method for Mpox HIV and Mpox Coinfection Previous STIs Sexual
Behavior
Alpalhão M, et al. [12] 2022 Case series Portugal 42 HIV: 37.7 ± 9.2 a M (n = 42) NR 22 NR MSM (n = 37)
Without-HIV: 32.5 ± 8.1 a
Antironi A, et al. [13] 2022 Case reports Italy 4 Median: 30 M (n = 4) RT-PCR 2 Syphilis (n = 3),
HBV (n = 1),
HCV (n = 1)		 MSM (n = 4)
Boesecke C, et al. [15] 2022 Case report Germany 1 40 M (n = 1) RT-PCR 1 Syphilis NR
Bížová B, et al. [14] 2022 Case report Czech Republic 1 34 M (n = 1) RT-PCR 1 Syphilis MSM (n = 1)
Brites C, et al. [16] 2022 Case reports Brazil 2 37
31		 M (n = 2) RT-PCR 1 NR MSM (n = 2)
Brundu M, et al. [17] 2022 Case report Italy 1 35 M (n = 1) RT-PCR 1 NR MSM (n = 1)
Catála A, et al. [18] 2022 Cohort study Spain 185 38.7 ± 8.2 a M (n = 185) RT-PCR 78 Yes (n = 140) * MSM (n = 184)
Curran KG, et al. [19] 2022 Cohort study USA 1969 35 (30–42) b M (n = 1466)
F (n = 10)		 RT-PCR 755 Gonorrhea (n = 546), Chlamydia (n = 489), and Syphilis (n = 165) NR
de Baetselier I, et al. [20] 2022 Cases series Belgium 4 Range: 30–50 M (n = 4) RT-PCR 3 Yes (n = 3) * MSM (n = 3)
de Sousa D, et al. [21] 2022 Case report Portugal 1 24 M (n = 1) RT-PCR 1 No MSM (n = 1)
Perez-Duque M, et al. [53] 2022 Cases series Portugal 27 33 (22–51) c M (n = 27) RT-PCR 14 NR MSM (n = 18)
Gandrakota N, et al. [22] 2022 Case report USA 1 34 Male-to-Female transgender (n = 1) RT-PCR 1 Neurosyphilis MSM (n = 1)
Gedela K, et al. [23] 2022 Cases series UK 2 Range: 30–40 M (n = 2) RT-PCR 1 HSV (n = 2), and Chlamydia (n = 1) MSM (n = 2)
Girometti N, et al. [24] 2022 Cohort study UK 54 41 (34–45) b M (n = 54) RT-PCR 13 Syphilis (n = 14), HSV (n = 24) and Gonorrhea (n = 13) MSM (n = 54)
Gomez-Garberi M, et al. [25] 2022 Cases series Spain 14 42 (20–56) c M (n = 14) RT-PCR 8 Chlamydia (n = 2) Syphilis (n = 1), Gonorrhea (n = 1), Mycoplasma, HSV-2 (n = 1) MSM (n = 10)
Hammerschlag Y, et al. [26] 2022 Case report Australia 1 30 M (n = 1) RT-PCR 1 Syphilis (n = 1) MSM (n = 1)
Heskin J, et al. [29] 2022 Case reports UK 2 NR M (n = 2) RT-PCR 1 Negative MSM (n = 2)
Hermanussen L, et al. [27] 2022 Case series Germany 3 44 (31–54) c M (n = 3) RT-PCR 1 Syphilis (n = 1) MSM (n = 2)
Hernandez LE, et al. [28] 2022 Case report USA 1 37 M (n = 1) RT-PCR 1 Syphilis (n = 1) NR
Hoffman C, et al. [31] 2022 Cohort study Germany 546 39 (20–69) c M (n = 546) RT-PCR 256 Yes (n = 286) * MSM (n = 546)
Hoffmann C, et al. [30] 2022 Cohort study Germany 301 39 (20–64) c M (n = 301) RT-PCR 141 Yes (n = 177) * MSM (n = 301)
Huang S, et al. [32] 2022 Case report Taiwan 1 24 M (n = 1) RT-PCR 1 NR MSM (n = 1)
Iñigo-Martínez J, et al. [33] 2022 Case series Spain 508 35 (18–67) c M (n = 503)
F (n = 5)		 RT-PCR 225 NR MSM
(n = 397)
Lapa D, et al. [34] 2022 Case report Italy 1 39 M (n = 1) RT-PCR 1 NR MSM (n = 1)
Loconsole D, et al. [35] 2022 Case series Italy 10 36 (25–71) c M (n = 8)
F (n = 2)		 RT-PCR 4 NR MSM (n = 6), heterosexual intercourse (n = 3)
Mailhe M, et al. [36] 2022 Cohort study France 264 35 (30–41) b M (n = 262)
F (n = 1)
Trans (n = 1)		 RT-PCR 73 Yes (n = 209) * MSM (n = 245)
Matias WR, et al. [37] 2022 Cases series USA 3 20 (20–40) c M (n = 3) RT-PCR 1 Gonococcal urethritis (n = 1) MSM (n = 3)
Rodrigues Menezes Y, et al. [38] 2022 Case report Brazil 1 41 M (n = 1) RT-PCR 1 NR MSM (n = 1)
Mileto D, et al. [39] 2022 Case report Italy 1 33 M (n = 1) RT-PCR 1 No NR
Moschese D, et al. [40] 2022 Case series Italy 32 38 (34–42) b M (n = 32) RT-PCR 17 NR MSM (n = 32)
Noe S, et al. [41] 2022 Case report Germany 2 26
32		 M (n = 2) RT-PCR 1 NR MSM (n = 2)
Nolasco S, et al. [42] 2022 Case report Spain 1 36 M (n = 1) RT-PCR 1 Syphilis MSM (n = 1)
Norz D, et al. [43] 2022 Cohort study Germany 10 Range: 20–50 M (n = 16) RT-PCR 2 NR MSM (n = 16)
Ogoina D, et al. [44] 2020 Cohort study Nigeria 40 32 (28–54) c M (n = 31)
F (n = 9)		 RT-PCR and
IgM serology		 9 NR NR
Ogoina D, et al. [45] 2018 Case series Nigeria 21 29 (6–45) c M (n = 17)
F (n = 4)		 RT-PCR and
IgM serology		 2 Syphilis (n = 2/8) NR
Ogoina D, et al. [46] 2022 Case series Nigeria 16 28 (22–43) c M (n = 12)
F (n = 6)		 RT-PCR and IgM serology 3 Yes (n = 4) * Heterosexual intercourse (n = 16)
Oprea C, et al. [47] 2022 Case report Romania 1 26 M (n = 1) RT-PCR 1 No MSM (n = 1)
Oprea C, et al. [48] 2022 Case report Romania 1 30 M (n = 1) RT-PCR 1 Syphilis (n = 1) MSM (n = 1)
Orviz E, et al. [49] 2022 Descriptive Spain 48 35 (29–44) b M (n = 48) RT-PCR 19 Gonorrhea (n = 6), Syphilis (n = 4)), and Mycoplasma genitalium (n = 1) MSM (n = 42)
Paparizos V, et al. [50] 2022 Case report Greece 1 59 M (n = 1) RT-PCR 1 No MSM (n = 1)
Patel A, et al. [51] 2022 Descriptive UK 197 38 (32–42) b M
(n = 197)		 RT-PCR 70 Gonorrhea (n = 43/161), Chlamydia (n = 13/161),
Syphilis (n = 6/163), and
HSV (n = 11/157)		 MSM
(n = 197)
Patrocinio-Jesus R, et al. [52] 2022 Case report Portugal 1 31 M (n = 1) RT-PCR 1 No MSM(n = 1)
Pfäfflin F, et al. [54] 2022 Cases series Germany 6 Range: 21–50 M (n = 6) RT-PCR 2 Gonorrhea (n = 3) and Syphilis (n = 1) MSM (n = 6)
Philpott F, et al. [55] 2022 Descriptive USA 1195 35 (30–41) b M (n = 1178)
F (n = 5)
Transgender man (n = 3)
Transgender woman (n = 5)		 RT-PCR 490 NR MSM (n = 337)
Pisano L, et al. [57] 2022 Case report Italy 1 45 M (n = 1) RT-PCR 1 NR MSM (n = 1)
Pipitò L, et al. [56] 2022 Case reports Italy 2 45
69		 M (n = 2) RT-PCR 2 Syphilis (n = 2), Gonorrhea (n = 1), and HCV (n = 1) MSM (n = 2)
Quattri E, et al. [58] 2022 Case reports Italy 2 35
29		 M (n = 2) RT-PCR 1 Syphilis (n = 2) and Gonorrhea (n = 1) MSM (n = 2)
Raccagni AR, et al. [59] 2022 Cases series Italy 36 41.5 (31.25–35.5) b M (n = 36) RT-PCR 15 Yes (n = 4) * MSM (n = 36)
Tarin-Vicente EJ, et al. [60] 2022 Cohort study Spain 181 37 (31–42) b M (n = 175)
F (n = 6)		 RT-PCR 72 Syphilis (n = 13) and Chlamydia (n = 10) MSM (n = 166) and
MSW (n = 15)
Thornhill JP, et al. [61] 2022 Cases series 16 countries 528 38 (18–68) c M (n = 527)
Trans (n = 1)		 RT-PCR 218 Gonorrhea (n = 32/377),
Chlamydia (n = 20/377),
Syphilis (n = 33/377),
HSV (n = 3/377),
Lympho-granuloma venereum (n = 2/377),
Chlamydia and Gonorrhea (n = 5/377)		 Heterosexual (n = 9)
Homosexual (n = 509)
Bisexual (n = 10)
Vusirikala A, et al. [62] 2022 Descriptive UK 45 40 (32–43) b M (n = 45) RT-PCR 11 Yes (n = 27) * MSM (n = 45)
Yakubovsky M, et al. [63] 2022 Descriptive Israel 26 34 (24–53) c M (n = 26) RT-PCR 7 Gonorrhea (n = 3) and C. trachomatis (n = 3) MSM (n = 26)
Zlámal M, et al. [64] 2022 Case report Czech Republic 1 38 M (n = 1) RT-PCR 1 HSV, Syphilis, Chlamydia, Gonorrhea, and HCV MSM (n = 1)
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Mpox: Monkeypox; UK: United Kingdom; USA: United States of America; MSM:  men who have sex with men; STI: sexually transmitted infection; HIV: human immunodeficiency virus; HBV: hepatitis B virus, HCV: hepatitis C virus, HSV: herpes simplex virus, RT-PCR: Polymerase chain reaction with reverse transcriptase; M/F: Male/Female; NR: No report. a Media ± SD. b Median (IQR). c Median (Range). * NS: Not Specified.

Table 3.

Characteristics of eligible studies. HIV status, clinical manifestations, localization, antiretroviral therapy, viral load, CD4+ T-cell count, treatment and outcomes.

Author N° of
Patients		 HIV and Mpox
Coinfection		 Clinical Manifestations Localization of Skin Lesions Antiretroviral Therapy Mpox and Acute HIV HIV Viral Load CD4+ T-Cell Count (cells/μL) Treatment Outcome
Alpalhão M, et al. [12] 42 22 Fever (n = 22), myalgias/arthralgias (n = 23), headache (n = 21), lymphadenopathy (n = 28) Genital (n = 28), perianal (n = 22), and perioral (n = 12) Yes (n = 22) No (n = 1) NR NR NR Recovered (n = 42)
Antinori A, et al. [13] 1 Yes Skin lesions and lymphadenopathy Genital, thorax and calf area Yes No (n = 1) NR NR Ciprofloxacin, acyclovir, and benzylpenicillin Recovered
2 No Skin lesions, fever, asthenia, and lymphadenopathy Anal, back, legs and foot sole Anti-inflammatory and antihistaminic drugs Recovered
3 Yes Skin lesions and fever Anal, head, thorax, legs, arms, hand, and genital area Yes No (n = 1) NR NR NR Recovered
4 No Skin lesions, myalgia Genital and pubic area NR Recovered
Boesecke C, et al. [15] 1 Yes Skin lesions Nose, penis, and oral mucosa Bictegravir/emtricitabine/tenofovir alafenamide Yes (n = 1) NR 127 Oral tecovirimat 600 mg bid for 7 days and ceftriaxone 2 g intravenous for 10 days Recovered
Bížová B, et al. [14] 1 Yes High fever, chills, lymphadenopathy, rash, painless perianal erosions, painless ulceration on his left tonsil, and perianal umbilicated papules Perianal and left side of the body NR No (n = 1) NR NR Cephalosporins Recovered
Brites C, et al. [16] 1 Yes Skin lesions, fever, chills, myalgia, lymphadenopathy, and urethral burning sensation during urination Forehead, nose, thorax, left leg, glans, and scrotal sac Lamivudine/tenofovir/efavirenz No (n = 1) Undetectable 604 Doxycycline and ceftriaxone Recovered
2 NR Skin lesions, fever, headache, back pain, and lymphadenopathy Legs, trunk, hands, and perianal area - - - - - Recovered
Brundu M, et al. [17] 1 Yes Skin lesions, fever, lymphadenopathy, chills, myalgia, headache, malaise, sore throat, and episodes of rectal bleeding Perianal, abdomen, chest, and back Darunavir/cobicistat/emtricitabine /tenofovir alafenamide Yes (n = 1) NR NR Analgesics Recovered
Catála A, et al. [18] 185 78 Skin lesions (n = 185), lymphadenopathy (n = 104), fever (n = 100), asthenia (n = 81), myalgia (n = 81), headache (n = 59), proctalgia (n = 40), throat ache (n = 34), arthralgia (n = 21), lumbar pain (n = 12), and oral ulcer (n = 10) Genital (n = 98), face (n = 72), arms (n = 70), perianal (n = 62), legs (52), thorax (n = 47), pubis (n = 30), abdomen (n = 29), back (n = 28), mouth (n = 26), plantar (22), palmar (n = 12), and eyelids (n = 2) NR NR Detectable viral load (n =  63) CD4 count: 698 (549–930) a
CD4 nadir: 396 (249–575) a 		NR Recovered (n = 185)
Curran KG, et al. [19] 1969 755 NS NR Yes (n = 713) Yes (n = 19) <200 copies/mL (n = 618) 639 (452–831) a
<350 (n = 91)		 NR Recovered (n = 1969)
de Baetselier I, et al. [20] 4 3 Asymptomatic (n = 3), Painful vesicular perianal rash (n = 1) Perianal (n = 1) Yes (n = 3) NR Viral load <20 µL (n = 3) >350 (n = 3) NR Recovered (n = 4)
de Sousa D, et al. [21] 1 Yes Skin lesions, fatigue, anal pain, lymphadenopathy, and fever Perianal, genital, mouth, face, and trunk No (n = 1) Yes (n = 1) >10,000,000 copies/mL 208 Paracetamol, tramadol, and fusidic acid cream Recovered
Perez-Duque M, et al. [53] 27 14 Exanthema (n = 14), inguinal
lymphadenopathy (n = 14), fever (n = 13),
genital ulcers (n = 6), genital vesicles (n = 6), asthenia (n = 7), headache (n = 7), and myalgia (n = 5)		 Genital (n = 6), anal (n = 4) NR NR NR NR NR Recovered (n = 27)
Gandrakota N, et al. [22] 1 Yes Skin lesions, anal pain, headache, fever, photophobia, neck stiffness, and bilateral lower extremity weakness Perianal Irregular No (n = 1) NR 200 Tecovirimat, penicillin, vancomycin, ceftriaxone, ampicillin, doxycycline, and dexamethasone Recovered
Gedela K, et al. [23] 2 1 Myalgia (n = 2), fever (n = 2), rectal pain (n = 2), lymphadenopathy (n = 2), skin lesions (n = 1), and throat pain (n = 1) Perianal (n = 1) Yes (n = 1) NR NR NR Aciclovir (n = 2), paracetamol (n = 2), topical lidocaine (n = 2) ibuprofen (n = 1), codein (n = 1), and morphine (n = 1) Recovered (n = 2)
Girometti N, et al. [24] 54 13 Skin lesions (n = 54), Fatigue (n = 36), fever (n = 31), lymphadenopathy (n = 30), myalgia (n = 16), and sore throat (n = 11) Genital (n = 33), perianal (n = 24), upper and lower extremities (n = 27), facial (n = 11), oropharyngeal (n = 4), and torso (n = 14) Yes (n = 13) Yes (n = 2) <50 copies/mL (n = 11), 200–500 copies/mL (n = 2) >500 (n = 13) Ceftriaxone (n = 3), doxycyclin (n = 2), metronidazole (n = 1), and tecovirimat (n = 1) Recovered (n = 54)
Gomez-Garberi M, et al. [25] 14 8 Skin lesions (n = 14), lymphadenopathy (n = 8), penile oedema (n = 6), fever (n = 5), malaise (n = 4), proctalgia (n = 1), and rectal itching (n = 1) Genital (n = 12), inguinal (n = 1), and perianal (n = 1) Yes (n = 8) Yes (n = 1) NR Median: 663 Antihistamines, analgesics, and nonsteroidal anti-inflammatory drugs (n = 14) and surgical (n = 2) Recovered (n = 14)
Hammerschlag Y, et al. [26] 1 Yes Skin lesions, fever, lymphadenopathy and general malaise Penis, trunk, face, extremities,
hand, calf, and nasal throat		 Abacavir/lamivudine/dolutegravir No (n = 1) < 100 copies/mL 700 Ceftriaxone,
doxycycline,
cephalexin, and oral
analgesia		 Recovered
Heskin J, et al. [29] 2 1 Skin lesions (n = 2) Genital (n = 1), pubic (n = 1),
oral and buccal mucous
membranes (n = 1), perioral (n = 1), and perianal (n = 1)		 Yes (n = 1) No (n = 1) NR NR Oral antiviral, antibacterial medication (ceftriaxone) (n = 2) Recovered (n = 2)
Hermanussen L, et al. [27] 1 No Skin lesions, fever, and malaise Face, hairy scalp, trunk, extremities, oral, palmar, and plantar regions - - - NR Tecovirimat, amoxicillin and clavulanic acid Recovered
2 No Skin lesions, lymphadenopathy, and myalgia Trunk and extremities - - - NR Tecovirimat and penicillin Recovered
3 Yes Skin lesions, fever, malaise, and weakness All over the body, but sparing the genital area Irregular No (n = 1) 1.29 × 106 copies/mL 50 Tecovirimat Recovered
Hernandez LE, et al. [28] 1 Yes Skin lesions Trunk, upper and lower extremities, groin, and perianal region Emtricitabine/tenofovir /doravarine/darunavir/cobicistat No (n = 1) <20 copies/mL 262 Tecovirimat, doxycycline, ceftriaxone, and valacyclovir Recovered
Hoffman C, et al. [31] 256 256 Fever (n = 126), headache and pain in the limbs (n = 98), night sweats (n = 40), and lymph node swelling (n = 95) Genital (n = 110), anal (n = 127), oral, perioral, head and neck (n = 64), and extremities and/or trunk (n = 92) NR Yes (n = 1) >50 copies/mL (n = 10), >200 copies/mL (n = 4) 691 (185–1603) b
<500 (n = 42) and <350 (n = 7)		 NR Recovered (n = 256)
232 (PrEP User) 0 Fever (n = 118), headache and pain in the limbs (n = 91), night sweats (n = 30), and lymph node swelling (n = 95) Genital (n = 114), anal (n = 116), oral, perioral, head and neck (n = 47), and extremities and/or trunk (n = 90) - - - - NR Recovered (n = 232)
58 (Without HIV or PrEP) 0 Fever (n = 28), headache and pain in the limbs (n = 19), night sweats (n = 3), and lymph node swelling (n = 23) Genital (n = 43), anal (n = 14), oral, perioral, head and neck (n = 12), and extremities and/or trunk (n = 14) - - - - NR Recovered (n = 58)
Hoffmann C, et al. [30] 301 177 Fever (n = 168/274), headache and pain in the limbs (n = 126/270), night sweats (n = 53/266), and lymph node swelling (n = 116/264) Genital (n = 146/298), anal (n = 152/299), oral, perioral, and head (n = 72/296), and extremities and/or trunk (n = 122/292) NR NR <50 copies/mL (n = 123/130), 50–200 copies/mL (n = 4/130), ≥200 copies/mL (n = 3/130) <350 (n = 4/127), 350–500 (n = 21/127), and ≥500 (n = 102/127) NR Recovered (n = 301)
Huang S, et al. [32] 1 Yes Skin lesions, lymphadenopathy, fever, sore throat, and myalgia Face, limbs, trunk, genital, and perianal Yes (n = 1) No (n = 1) NR 517 NR Recovered
Iñigo-Martínez J, et al. [33] 508 225 Skin lesions (n = 498), fever (n = 324),
lymphadenopathy (n = 311), asthenia
(n = 238), myalgia (n = 185), headache
(n = 162), odynophagia (n = 143), and
proctitis (n = 81)		 Anogenital and/or perineal area
(n = 359), legs and/or arms
(n = 222), face (n = 177), chest
and/or abdomen (n = 159), back
(n = 132), palms and/or plants
(n = 124)		 NR NR NR NR NR Recovered (n = 508)
Lapa D, et al. [34] 1 Positive Skin lesions, fever Head, thorax, legs, arms, hand, and penis Dolutegravir/lamivudine No (n = 1) NR NR NR Recovered
Loconsole D, et al. [35] 10 6 Skin lesions (n = 10), fever (n = 10), shivering and sweating (n = 10), and lymphadenopathy (n = 10) Genital (n = 7), face (n = 6), palms (n = 3), arms (n = 4), trunk (n = 4), back (n = 3), and oral (n = 2) NR NR NR NR NR Recovered (n = 10)
Mailhe M, et al. [36] 264 73 Skin lesions (n = 264), lymphadenopathy (n = 174), fever (n = 171), pharyngitis (n = 51), angina (n = 41), respiratory signs (n = 31), and headaches (n = 89) Genital area (n = 135), limbs (n = 121), trunk (n = 105), perianal (n = 100), face (n = 88), and palmoplantar area (n = 36) NR NR NR >500 (n = 4) Cidofovir (n = 1), valaciclovir (n = 1), tobramycin (n = 1), ocular dexamethasone (n = 1), ganciclovir (n = 1), opioids (n = 6), acetaminophen (n = 9), surgical (n = 4) Recovered (n = 264)
Matias WR, et al. [37] 1 No Skin lesions, lymphadenopathy, fever, chills, and general malaise Penis, pubis, and arm - - - - Tecovirimat Recovered
2 Yes Skin lesions, lymphadenopathy, fever, chills, myalgias, left tonsillar pain, and odynophagia Forearms and hands Yes (n = 1) No (n = 1) Suppressed viral load >500 Tecovirimat Recovered
3 No Skin lesions, lymphadenopathy, malaise, and subjective fevers Penis, chest, and arm - - - - Tecovirimat Recovered
Rodrigues Menezes Y, et al. [38] 1 Yes Skin lesions, lymphadenopathy, dyspnea, penis and glans edema, throat pain, diarrhea, weakness, and malaise Chest, abdomen, back, upper and lower limbs, palms of the hands, soles of the feet, genitalia, perineum, anorectal region, tongue, and oropharynx Yes No (n = 1) Undetectable 53 Meropenem and vancomycin Death
Mileto D, et al. [39] 1 Yes Skin lesions, fever, lymphadenopathy, asthenia, malaise, faryngodynia, sneezing, and anorexia Face, both elbows, the trunk, the buttock and the right foot Dolutegravir/rilpivirine No (n = 1) <20 copies/mL 771 NR Recovered
Moschese D, et al. [40] 32 0 Skin lesions (n = 7), fever (n = 3), lymphadenopathy (n = 2), fatigue, asthenia, and malaise (n = 9), back pain (n = 2), myalgia (n = 1), abdominal symptoms (n = 2), sore throat (n = 2), and headache (n = 5) Genital (n = 2), face (n = 6), oral (n = 2), anal/perianal (n = 8), palms (n = 3), and soles (n = 1) - - - NR NR Recovered (n = 15)
15 Skin lesions (n = 9), fever (n = 6), lymphadenopathy (n = 1), fatigue, asthenia, and malaise (n = 11), back pain (n = 3), myalgia (n = 1), abdominal symptoms (n = 2), sore throat (n = 4), and headache (n = 2) Genital (n = 9), face (n = 10), oral (n = 1), anal/perianal (n = 10), and palms (n = 1) Yes (n = 17) NR <50 copies/mL (n = 16) 678 (526–933) a NR Recovered (n = 17)
Noe S, et al. [41] 1 Yes Skin lesions, malaise, fever, arthralgia, myalgia, back pain, headache, dysphagia, and
presence of white spots on his tonsils.		 Trunk, extremities, and head Bictegravir/emtricitabine/tenofovir alafenamide NR NR NR NR Recovered
2 No Skin lesions, fever, fatigue, cough, inguinal
lymphadenopathy, and anal pain		 Trunk - - - - Topical zinc oxide suspension Recovered
Nolasco S, et al. [42] 1 Yes Skin lesions, fever, sore throat, fatigue, headache and lymphadenopathy Perianal, torso, lower limbs, palms, face and glutes Dolutegravir/abacavir/lamivudine Yes
(n = 1)		 234,000 copies/mL 812 Sotrovimab Recovered
Norz D, et al. [43] 10 2 Skin lesions (n = 10), lymphadenopathy (n = 5), fever (n = 3), malaise (n = 3), muscle and joint pains (n = 2), penile swelling and pain (n = 1), and anal pain (n = 1) Genital (n = 8), perianal (n = 3), oral (n = 2), legs (n = 2), anal (n = 2), arms (n = 2), back (n = 1), and face (n = 1) Bictegravir/Emtricitabin/Tenofovir alafenamide (n = 1)
Dolutegravir/lamivudin (n = 1)		 NR 22 copies/mL (n = 1) and not detectable (n = 1) 360 (n = 1), and 279 (n = 1) Local therapy (n = 10), antibiotic therapy (n = 2), analgesic (n = 2) Recovered (n = 10)
Ogoina D, et al. [44] 40 9 Skin lesions (n = 40), fever (n = 36), lymphadenopathy (n = 35), body aches (n = 25), headache (n = 19), sore throat (n = 18), pruritus (n = 15), and conjunctivitis and photophobia (n = 9). Face (97.5%), trunk (92.5%), arms (87.5%), legs (85%), genitalia (67.5%), scalp (62.5%), palms (55%), soles (50%), mouth (37.5%), and eyes (25%) Yes (n = 5) Yes (n = 4) 4798 copies/mL (n = 1) 20 (n = 1), 55 (n = 1), 300 (n = 1), 101 (n = 1), 354 (n = 1), and 357 (n = 1) Symptomatic and supportive care according to the Nigerian interim guidelines for management of HMPOX HIV: death (n = 2)
Without-HIV: death (n = 3)
Ogoina D, et al. [45] 21 2 Skin lesions (n = 21), fever (n = 18), itching (n = 14), malaise (n = 13), headache (n = 12), lymphadenopathy (n = 13), sore throat (n = 9), myalgia (n = 5), conjuctivitis (n = 4), and diarrhoea (n = 1) NR NR Yes (n = 2/8) NR 354 (n = 1), and 280 (n = 1) NR Recovered (n = 20)
Death (n = 1, suicide)
Ogoina D, et al. [46] 16 3 Skin lesions (n = 7), and fever (n = 9) NR NR NR NR NR NR NR
Oprea C, et al. [47] 1 Yes Skin lesions, fever, lymphadenopathy, chills, rectal pain, and dysphagia Genital, perineal, anal, neck, trunk, and upper and lower limbs 3TC/ABC/DTG No (n = 1) 40 copies/mL 988 Symptomatic treatment, fluids and topic treatment Recovered
Oprea C, et al. [48] 1 Yes Skin lesions, fever, lymphadenopathy, malaise, nausea, loss of appetite, and jaundice Genital, anal, trunk, lumb., face, ear flap, limbs, palms, soles, and oral mucosa Tenofovir/lamivudine/dolutegravir (adherence problems) No (n = 1) 2820 copies/mL 936 Glucose, arginine, benzathine benzylpenicillin, dexamethasone 8 mg/day, vitamin K and fresh frozen plasma Recovered
Orviz E, et al. [49] 48 19 Skin lesions (n = 45), fever (n = 25), asthenia (n = 32), myalgia
(n = 25), lymphadenopathy
(n = 39), headache
(n = 25), proctitis (n = 13), urethritis
(n = 7), rash (n = 4), nasal congestion
(n = 4), and cough (n = 8)		 Genital (n = 26), upper
extremities (n = 20), perianal
(n = 17), trunk (n = 16), facial
(n = 12), periorally (n = 9),
lower extremities (n = 10), and
palms and soles (n = 2)		 Yes (n = 18) Yes (n = 1) NR NR NR Recovered (n = 48)
Paparizos V, et al. [50] 1 Yes Skin lesions, fever, lymphadenopathy, myalgia and fatigue Genital Yes (n = 1) No (n = 1) < 20 copies/mL 648 Topical octenidine and antibiotic ointment Recovered (n = 1)
Patel A, et al. [51] 197 70 Mucocutaneous manifestations (n = 197), fever (n = 122), lymphadenopathy (n = 114), headache (n = 49), fatigue/lethargy (n = 46), myalgia (n = 62), arthralgia (n = 21), back pain (n = 21), and rectal pain or pain on defecation (n = 71) Face (n = 71), trunk (n = 70), arms/legs (n = 74), hands/feet (n = 56), genitals (n = 111), anus or perianal area (n = 82), and oropharyngeal (n = 27) Yes (n = 64/70) Yes (n = 1) <200 copies/mL (n = 55/70) 664 (522–894) b Paracetamol, ibuprofen, opioids, and lidocaine gel Recovered (n = 197)
Patrocinio-Jesus R, et al. [52] 1 Yes Skin lesions, lymphadenopathy, fever and sore throat Genital, face and hands NR NR NR NR NR Recovered (n = 1)
Pfäfflin F, et al. [54] 1 Yes Skin lesions, fever, perianal pain, anal abscess, and
lymphadenopathy		 Limbs Yes NR NR 870 Ibuprofen Recovered
2 No Skin lesions, fever, malaise, anal pain, and anal fissure Left arm - - - - Metamizole, tramadol, lidocaine topical Recovered
3 No Skin lesions, anal pain, rectal ulcer, and proctitis Limbs - - - - Ibuprofen, metamizole, lidocaine topical Recovered
4 No Skin lesions, fatigue, anal pain, and anal ulcer Arms, trunk, genital - - - - Metamizole, lidocaine topical Recovered
5 No Skin lesions, fever, malaise, myalgia, sweats, anal pain, inflammation of rectum and anal
canal		 Head, neck, trunk, limbs - - - - Metamizole, lidocaine topical Recovered
6 Yes Skin lesions, anal ulcer, myalgia, fever, malaise, anal pain, and proctitis Legs Yes NR NR > 500 Metamizole, lidocaine topical Recovered
Philpott F, et al. [55] 1195 490 Skin lesions (n = 1004), fever (n = 596), chills
(n = 550), lymphadenopathy (n = 545),
malaise (n = 531), myalgia (n = 507),
headache (n = 469), rectal pain (n = 201),
pus or blood in stools (n = 184),
abdominal pain (n = 96), rectal bleeding
(n = 90), tenesmus (n = 90), and vomiting
or nausea (n = 83)		 Genital (n = 333), arms
(n = 284), face (n = 276), legs
(n = 265), perianal (n = 225),
mouth, lips, or oral mucosa
(n = 179), palms of hands
(n = 157), trunk (n = 156), neck
(n = 130), head (n = 97), and
soles of feet (n = 77)		 NR NR NR NR NR NR
Pisano L, et al. [57] 1 Yes Skin lesions, lymphadenopathy, asthenia, headache, mild myalgia and cold. Face, neck, genital, limbs and trunk Elvitegravir/tenofovir/emtricitabine/cobicistat No Undetectable NR NR Recovered (n = 1)
Pipitò L, et al. [56] 1 Yes Skin lesions, fever, malaise, sore throat and painful cervical lymphadenopathy Oral mucosa and trunk Yes NR Undetectable NR NR Recovered
2 Yes Skin lesions, sore throat and painful cervical lymphadenopathy Oral mucosa and nipple Yes NR Undetectable NR NR Recovered
Quattri E, et al. [58] 1 Yes Skin lesion Genital NR NR NR NR NR Recovered
2 No Skin lesion Genital - - - - NR Recovered
Raccagni AR, et al. [59] 36 15 Skin lesions (n = 36) Genital (n = 13), rectal (n = 18), and cutaneous (n = 20) NR NR NR NR NR Recovered (n = 36)
Tarin-Vicente EJ, et al. [60] 181 72 Skin lesions (n = 181), lymphadenopathy (n = 153), influenza-like illness (n = 147), fever (n = 131), headache (n = 96), and sore throat (n = 66) Genital (n =100), perianal area (n = 66), oral ulcer (n = 45), perioral (n = 51), hands and feet (n = 108), trunk and extremities (n = 104) Yes (n = 71) NR NR <500 (n = 8) Cidofovir (n = 6) Recovered (n = 181)
Thornhill JP, et al. [61] 528 218 Rash or skin lesions (n = 500), fever (n = 330), lymphadenopathy (n = 295), lethargy or exhaustion (n = 216), myalgia (n = 165), headache (n = 145), pharyngitis (n = 113), low mood (n = 54), and proctitis or anorectal pain (n = 75). Anogenital area (n = 383), trunk or limbs (n = 292), face (n = 134), palms or soles (n = 51), and mucosal lesions (n = 217). Tenofovir-based three-drug regimen (n = 102/210), abacavir-based three-drug regimen (n = 20/210), zidovudine-based three-drug regimen (n = 2/210), two-drug regimen (n = 48/210) NR < 50 copies/mL (n = 180/190), < 200 copies/mL (n = 185/190) 680 (513–861) a Cidofovir (n = 12), tecovirimat (n = 8), and vaccinia immune globulin (n = 1) Recovered (n = 528)
Vusirikala A, et al. [62] 45 11 NR NR Yes (n = 11) NR Undetectable (n = 10) NR NR Recovered (n = 45)
Yakubovsky M, et al. [63] 26 7 Skin lesions (n = 26), proctitis (n = 26), fever (n = 19), and inguinal lymphadenopathy (n = 17) Anorrectal (n = 19), genital (n = 11), and other (n = 18) NR NR NR NR NR Recovered (n = 26)
Zlámal M, et al. [64] 1 Yes Skin lesions, fever, rash, groin lymphadenopathy, and rectal pain Anal, perianal, and trunk Yes (n = 1) No Undetectable (n = 1) >200 Valaciclovir, ceftriaxone, azithromycin, and metronidazole Recovered (n = 1)
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Mpox: Monkeypox; NR: No report. a Median (IQR). b Median (Range).

3.3. Demographical Characteristics and Diagnostic Method for Monkeypox

Males accounted for 91.44% (n = 5802) of the total cases registered with Mpox [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]. The patients ranged in age from 18 to 71 years. In addition, 51.36% (n = 3259) presented sexual behaviors of being MSM [12,13,14,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,40,41,42,43,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]. The most frequent previous or current sexually transmitted infections were 40.32% HIV (n = 2558) [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64], 10.26% Gonorrhea (n = 651) [19,24,25,37,49,51,54,56,58,61,63,64], 3.81% Syphilis (n = 242) [13,14,15,19,22,24,25,26,27,28,42,45,48,49,51,54,56,58,60,61,64], and less than 1% HSV (n = 42) [23,24,25,51,61,64]. Overall, almost all confirmed Mpox cases were diagnosed by PCR [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64] and only three studies conducted in Nigeria used positive IgM serology [44,45,46] (Table 2).

3.4. Clinical Symptoms, Skin Lesion Localization, CD4+ T-Cells, Treatment and Outcomes

The most frequent clinical manifestations in patients with Mpox were: 50% skin lesions (n = 3173) [13,14,15,16,17,18,20,21,22,23,24,25,26,27,28,29,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,63,64], 38.53% fever (n = 2445) [12,13,14,16,17,18,21,22,23,24,25,26,27,30,31,32,33,34,35,36,37,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,60,61,63,64], 35.56% lymphadenopathy (n = 2256) [12,13,14,16,17,18,21,23,24,25,26,27,30,31,32,33,35,36,37,38,39,40,41,42,43,44,45,47,48,49,50,51,52,53,54,55,56,57,60,61,63,64], and 23.61% headache (n = 1498) [12,16,17,18,22,30,31,33,36,40,41,42,44,45,49,51,53,55,57,60,61](Table 3). The most frequent locations of lesions were: 33.16% genitalia (n = 2104) [12,13,15,16,18,21,24,25,26,27,29,30,31,32,33,34,35,36,37,38,40,43,44,47,48,49,50,51,52,53,54,55,57,58,59,60,61,63], 28.51% anus or perianal area (n = 1809) [12,13,14,16,17,18,20,21,22,23,24,25,28,29,30,31,32,33,36,38,39,40,42,43,47,48,49,51,53,55,59,60,61,63,64], and 11.49% mouth, lips, or oral mucosa (n = 729) [12,15,18,21,24,27,29,30,31,35,38,40,43,44,45,46,48,49,51,55,56,60] (Table 3). The majority of patients received empirical treatment targeting sexually transmitted diseases and symptomatic, and only Mpox-targeted treatment received: cidofovir (n = 19) [36,60,61] and tecovirimat (n = 18) [15,22,24,27,28,37,61]. In HIV-positive patients, 428 patients were reported to be receiving ART [12,15,16,17,19,20,23,24,25,26,28,29,32,34,37,38,39,40,41,42,43,44,47,48,49,50,51,54,56,57,60,61,62,64], 114 had a CD4+ T-cell count <350/μL [15,19,21,22,27,28,30,31,38,43,44,45], and 15 had a viral load >200 copies/mL [21,24,27,30,31,42,44,48,51,61]. Finally, six deaths were reported, one of these being of an HIV-positive patient with an undetectable viral load and a CD4+ T-cell count of 74/μL who was receiving chemotherapy for diffuse large B-cell lymphoma with metastases to the spine, skull, and liver [38] and two others in HIV-1 positive patients, one who developed sepsis and another with a CD4+ T-cell count < 20/μL and who died after multiple episodes of seizures [44].

4. Discussion

Monkeypox emerged this last year as an important epidemiological topic to approach due to the rapid spread of confirmed cases [5]. Likewise, diverse investigations identified the association between Mpox and people living with HIV [65,66]. There have been reports of higher HIV and other STI prevalence in the current worldwide Mpox outbreak, which has largely afflicted gay, bisexual, and MSM people [19]. A theoretical idea that HIV may enhance Monkeypox virus transmission and vice versa was also identified [44]. However, there is still limited scientific information about Mpox co-infection with HIV. For that reason, we summarize the cases of this co-infection in order to have a better epidemiological view. In this study, the epidemiological situation of HIV and Mpox co-infection was determined.

We assessed 53 studies. Our principal findings reveal that most of the population (91.44%) was male. Moreover, the main diagnostic test for Mpox was PCR, and that finding shows the relevance of this test in the diagnosis of Mpox. Another relevant result is that 51.36% of the cases were MSM, which demonstrate the importance to explore this risk factor. The HIV and Mpox co-infection were 40.3%, and the most frequent clinical signs were skin lesions, fever, lymphadenopathy, and headache. Identifying all these characteristics or possible risk factors generates a better prescription of the early system of vaccination for Mpox. The Centers for Disease Control and Prevention (CDC) support the recommendation of the vaccine to people who have already been exposed to Mpox or someone who might be in risk of exposure [67].

The largest number of cases registered with co-infection of Mpox and HIV are male (91.44%), which is consistent with other reviews in which it is reported that the population most affected by Mpox are men [6,68,69,70]. The prevalence of Mpox and HIV co-infection was 40% of the cases. This could be due to the fact that most of the cases occurred in MSM (51%) and that MSM has a greater HIV prevalence than the overall population [19,71]. In addition, HIV-positive patients are more likely to attend a health care facility and have a diagnostic test for Mpox compared to HIV-negative patients [72]. However, the 40% prevalence reported in this systematic review exceeds the prevalence of HIV in MSM in the USA (23%) [19] and Europe (7.7%) [73]. This disparity would suggest that transmissibility could be higher in people with HIV [74]. Mpox can be transmitted by respiratory secretions, skin lesions, contaminated fomites and through seminal fluid [69,75]. Reda et al. [69] found that seminal fluid from Mpox-infected patients had a high Monkeypox virus DNA positivity rate (72.4%), behind the positivity rate of anogenital/rectal lesion samples (74.3%). Therefore, such sexual behaviors in HIV patients could predispose to Mpox infection.

Of the three reported deaths of patients with Mpox and HIV co-infection, two cases had a CD4+ T-cells count < 200/μL. Agrati et al. [76] found rapid activation and expansion of CD4+ and CD8+ T cells with effector memory phenotype and a good Th1 cell response that persisted even after clinical recovery in Mpox patients. However, it was also found that paucisymptomatic patients had a less active T-cell response [76]. This suggests a link between the immune response and clinical severity from Mpox. In addition, it was previously reported that Mpox has the ability to trigger a state of T-cell unresponsiveness via a unique major histocompatibility complex (MHC), the independent mechanism that prevents the activation of CD4+ and TCD8+ T-cell antiviral responses and cytokine production [77,78]. This is probably related to viral dissemination and clinical severity in the infected host. Therefore, a state of immunosuppression, characterized by a low CD4+ T-cell count and response in HIV patients, could be associated with clinical severity, dissemination, and mortality from Mpox infection.

Early and consistent ART delivery according to modern combination regimens reduces viraemia in HIV-infected individuals in a few weeks [79]. The level of viral suppression can be so high that viral evolution is halted and the immune system is restored [79]. In the study by Agrati et al. [76] it was found that the T-cell response in patients with Mpox did not differ according to HIV status. This was due to the fact that patients with Mpox and HIV had a good viroimmunological status. In addition, although there is currently no strong evidence to support the use of antiviral drugs directed against Mpox [80,81], such as tecovirimat or cidofovir, the CDC’s “Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection” [82] recommends the use of tecovirimat according to the viroimmunological status of the patient and thus avoid possible complications [83]. Therefore, in patients with HIV and Mpox co-infection it is necessary to start or continue the administration of ART and, if indicated, a therapy directed against Mpox such as tecovirimat. Potential drug interactions between ART and tecovirimat are not grounds for discontinuation of either [82].

Limitations and Strengths

Among the limitations of this systematic review is that most of the studies correspond to case reports and case series, while longitudinal observational studies are scarce. Therefore, in order to draw reliable conclusions about the severity and mortality of Mpox in HIV patients, it is necessary to have observational studies with an established control group and to control for different confounding factors, such as previous vaccination status or other comorbidities. Likewise, the information reported regarding HIV stage, antiviral therapy regimen, adherence to treatment, CD4+ T-cells counts and viral load is scarce. It would be important to perform subgroup analyses for these variables to determine their influence during disease development in patients with Mpox and HIV. The available research does not allow us to draw conclusions about the severity and mortality of Mpox in HIV patients. In terms of strengths, the current study had a rigorous methodology because it was carried out in accordance with the PRISMA criteria. Similarly, all steps for selecting research were carried out independently by two or more authors.

5. Conclusions

HIV and Mpox are spread through sexual contact and are more frequent in those who engage in male-male sexual behavior. Co-infection between HIV and Mpox occurred in 40.32%. Co-infection with these two viruses can be especially dangerous, as it can exacerbate the symptoms of both diseases and make them more difficult to treat.

Author Contributions

Conceptualization, B.O.-S., E.S.M.-M. and C.C.-R.; methodology, D.A.L.-F. and R.S.; software, J.J.B.; validation, A.R.-M. and N.A.; formal analysis, B.O.-S. and R.S.; investigation, D.A.L.-F.; resources, J.J.B.; data curation, C.C.-R.; writing—original draft preparation, B.O.-S., E.S.M.-M. and N.A.; writing—review and editing, D.A.L.-F., B.O.-S. and J.J.B.; visualization, A.R.-M.; supervision, N.A.; project administration, A.M., B.K.P. and R.S. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data included within the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Funding Statement

This research received no external funding.

Footnotes

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