中国药物警戒 ›› 2024, Vol. 21 ›› Issue (12): 1329-1336.
DOI: 10.19803/j.1672-8629.20240827
任秉青, 范子博, 张袁媛, 张伟, 陈志海*
收稿日期:2024-10-30
出版日期:2024-12-15
发布日期:2024-12-16
通讯作者:
*陈志海,男,主任医师,教授·博导,感染性疾病。E-mail: chenzhihai0001@126.com。陈志海,主任医师,教授,博士生导师,国家级人才项目获得者。首都医科大学附属北京地坛医院感染性疾病中心主任兼感染性疾病科主任,国家卫生健康委员会传染病标准专业委员会委员,中华预防医学会感染性疾病防控分会常务委员,中华医学会北京分会感染专业委员会副主任委员,北京中西医结合学会感染专业委员会主任委员。致力于各种急性传染病临床诊治研究30余年,作为国家卫生健康委员会、北京市卫健委专家参加全国各种重大传染病疫情处置。《中国药物警戒》期刊编委。
作者简介:任秉青,男,在读硕士,感染性疾病。
基金资助:REN Bingqing, FAN Zibo, ZHANG Yuanyuan, ZHANG Wei, CHEN Zhihai*
Received:2024-10-30
Online:2024-12-15
Published:2024-12-16
摘要： 目的 综述猴痘合并人类免疫缺陷病毒(HIV)/获得性免疫缺陷综合征（AIDS）感染的流行病学特征、临床表现、治疗现状及预防策略,以提高临床对该类患者的识别与诊治能力。方法 针对合并HIV/AIDS感染的猴痘患者流行病学和临床特点,从药物作用机制、现阶段研究等对治疗猴痘药物及疫苗进行总结。结果 2022年以来猴痘在全球多个国家和地区暴发流行,HIV感染者是猴痘病毒感染的高危人群,目前无特效疫苗和特异性治疗药物,一些小分子药物（特考韦瑞、西多福韦、布林西多福韦）、牛痘免疫球蛋白和疫苗（改良痘苗病毒安卡拉株、复制缺陷型天花疫苗）在研究和临床试验阶段表现出良好的抗病毒效力。结论 猴痘合并HIV/AIDS感染的病例在全球疫情中占有较高比例,小分子抗病毒药物、免疫球蛋白和预防性疫苗接种可用于患者进行治疗。
中图分类号:
任秉青, 范子博, 张袁媛, 张伟, 陈志海. 猴痘合并HIV/AIDS感染的临床诊治与药物研究进展[J]. 中国药物警戒, 2024, 21(12): 1329-1336.
REN Bingqing, FAN Zibo, ZHANG Yuanyuan, ZHANG Wei, CHEN Zhihai. Clinical Characteristics and Treatments of Monkeypox Infections in Patients with HIV/AIDS[J]. Chinese Journal of Pharmacovigilance, 2024, 21(12): 1329-1336.
| [1] HUANG Y, MU L, WANG W.Monkeypox: Epidemiology, Pathogenesis, Treatment and Prevention[J]. Signal Transduct Target Ther, 2022, 7(1): 373. [2] WHO. WHO Director-General's Statement at the Press Conference Following IHR Emergency Committee Regarding the Multi-Country Outbreak of Monkeypox-23 July 2022[EB/OL]. (2022-07-23)[2024-10-30]. https://www.who.int/news-room/speeches/item/who-director-general-s-statement-on-the-press-conference-following-IHR-emergency-committee-regarding-the-multi--country-outbreak-of-monkeypox--23-july-2022. [3] WHO. WHO Director-General Declares Mpox Virus a Public Health Emergency of International Concern[EB/OL]. (2022-08-14)[2024-10-30]. https://news.un.org/en/story/2024/08/1153176. [4] GIROMETTI N, BYRNE R, BRACCHI M, et al.Demographic and Clinical Characteristics of Confirmed Human Monkeypox Virus Cases in Individuals Attending a Sexual Health Centre in London, UK: An Observational Analysis[J]. Lancet Infect Dis, 2022, 22(9): 1321-1328. [5] European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Mpox, Joint Epidemiological Overview[EB/OL]. (2023-06-06) [2024-10-30]. https://monkeypoxreport.ecdc.europa.eu/. [6] BRYER JS, FREEMAN EE, ROSENBACH M.Monkeypox Emerges On A Global Scale: A Historical Review and Dermatologic Primer[J]. J Am Acad Dermatol, 2023, 88(5): e259. [7] KOWALSKI J, CIELNIAK I, GARBACZ-ŁAGOŻNA E, et al. Comparison of Clinical Course of Mpox among HIV-Negative and HIV-Positive Patients: A 2022 Cohort of Hospitalized Patients in Central Europe[J]. J Med Virol, 2023, 95(10) : e29172. [8] PHILPOTT D, HUGHES CM, ALROY KA, et al.Epidemiologic and Clinical Characteristics of Monkeypox Cases-United States[J]. MMWR Morb Mortal Wkly Rep, 2022, 71(32): 1018-1022. [9] PATEL A, BILINSKA J, TAM JCH, et al.Clinical Features and Novel Presentations of Human Monkeypox in A Central London Centre During the 2022 Outbreak: Descriptive Case Series[J]. BMJ, 2022, 378: e072410. [10] MITJÀ O, ALEMANY A, MARKS M, et al.Mpox in People with Advanced HIV Infection: A Global Case Series[J]. Lancet, 2023, 401(10380): 939-949. [11] O'SHEA J, FILARDO TD, MORRIS SB. Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection-United States, August 2022[J]. MMWR Morb Mortal Wkly Rep, 2022, 71(32): 1023-1028. [12] CHO CT, WENNER HA.Monkeypox Virus[J]. Bacteriol Rev, 1973, 7(1): 1-18. [13] TAQUET M, SKORNIEWSKA Z, DE DEYN T, et al.Cognitive and Psychiatric Symptom Trajectories 2~3 Years after Hospital Admission for COVID-19: A Longitudinal, Prospective Cohort Study in the UK[J]. Lancet Psychiatry,2024, 11(9): 696-708. [14] CDC. Detection of Monkeypox Outbreak in August 2023[EB/OL]. (2023-09-08)[2024-09-30]. http://m.chinacdc/jkzt/crb/yl/hd_13044/qxx/20230908_269405.html. [15] JEYARAMAN M, SELVARAJ P, HALESH MB, et al.Monkeypox: An Emerging Global Public Health Emergency[J]. Life (Basel), 2022, 2(10): 91-109. [16] MILLER MJ, CASH-GOLDWASSER S, MARX GE, et al.Severe Monkeypox in Hospitalized Patients-United States[J]. MMWR Morb Mortal Wkly Rep, 2022, 71(44): 1412-1417. [17] MA XY, ZHOU XY, YUAN H.Epidemiological Characteristics of Monkeypox Cases in Sichuan Province, 2023[J]. China Tropical Medicine(中国热带医学), 2024, 24(9): 1149-1152. [18] YINKA-OGUNLEYE A, DALHAT M, AKINPELU A, et al.Mpox (Monkeypox) Risk and Mortality Associated with HIV Infection: a National Case-Control Study in Nigeria[J]. BMJ Glob Health, 2023, 8(11):e013126. [19] DSOUZA VS, RAJKHOWA P, MALLYA BR, et al.A Sentiment and Content Analysis of Tweets on Monkeypox Stigma among the LGBTQ+ Community: A Cue to Risk Communication Plan[J]. Dialogues Health, 2023, 2: 100095. [20] LIN M, XIN Y, WANG J, et al.Analyzing Monkeypox Epidemic Drivers: Policy Simulation and Multi-Index Modelling Across 39 Nations[J]. J Glob Health, 2024, 18(2): 177-188. [21] MORAES-CARDOSO I, BENET S, CARABELLI J, et al.Immune Responses Associated with Mpox Viral Clearance in Men with and Without HIV in Spain: A Multisite, Observational, Prospective Cohort Study[J]. Lancet Microbe, 2024, 5(8): 100859. [22] HOFFMANN C, JESSEN H, BOESECKE C.Monkeypox in Germany[J]. Dtsch Arztebl Int, 2022, 119(33-34): 551-557. [23] ALPALHÃO M, SOUSA D, FRADE JV, et al. Human Immunodeficiency Virus Infection May be A Contributing Factor to Monkeypox Infection: Analysis of A 42-Case Series[J]. J Am Acad Dermatol, 2023, 88(3): 720-722. [24] BETANCORT-PLATA C, LOPEZ-DELGADO L, JAÉN-SANCHEZ N, et al. Monkeypox and HIV in the Canary Islands: A Different Pattern in A Mobile Population[J]. Trop Med Infect Dis, 2022, 7(10): 318. [25] ANGELO KM, SMITH T, CAMPRUBÍ-FERRER D, et al.Epidemiological and Clinical Characteristics of Patients with Monkeypox in the GeoSentinel Network: A Cross-Sectional Study[J]. Lancet Infect Dis, 2023, 23(2): 196-206. [26] ROPER, RL, GARZINO-DEMO, A, DEL-RIO, C. Monkeypox (Mpox) Requires Continued Surveillance, Vaccines, Therapeutics and Mitigating Strategies[J]. Vaccine, 41(20), 3171-3177. [27] HUGGINS J, GOFF A, HENSLEY L, et al.Nonhuman Primates are Protected from Smallpox Virus or Monkeypox Virus Challenges by the Antiviral Drug ST-246[J]. Antimicrob Agents Chemother, 2009, 53(6): 2620-2625. [28] Centers of Disease Control and Prevention. Information for Healthcare Providers on Obtaining and Using TPOXX (Tecovirimat) for Treatment of Monkeypox[EB/OL]. (2022-08-18)[2024-10-26].https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html. [29] JORDAN R, CHINSANGARAM J, BOLKEN TC, et al.Safety and Pharmacokinetics of the Antiorthopoxvirus Compound ST-246 Following Repeat oral Dosing in Healthy Adult Subjects[J]. Antimicrob Agents Chemother, 2010, 54: 2560-2566. [30] HALANI S, LEONG D, WU PE.Tecovirimat for Monkeypox[J]. CMAJ, 2022, 194(46): E1573. [31] SIEGRIST EA, SASSINE J Antivirals with Activity Against Mpox: A Clinically Oriented Review[J]. Clin Infect Dis, 2023, 76(1): 155-164. [32] DESAI AN, THOMPSON GR, NEUMEISTER SM, et al.Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection[J]. Jama, 328(13): 1348-1350. [33] SMITH, TG, GIGANTE CM, WYNN NT, et al.Tecovirimat Resistance in Mpox Patients, United States, 2022-2023[J]. Emerging Infectious Diseases, 2023, 29(12): 2426-2432. [34] RUSSO AT, GROSENBACH DW, CHINSANGARAM J, et al.An Overview of Tecovirimat for Smallpox Treatment and Expanded Anti-Orthopoxvirus Applications[J]. Expert Rev Anti Infect Ther, 2021, 19(3): 331-344. [35] FRENOIS-VEYRAT G, GALLARDO F, GORGÉ O, et al.Tecovirimat is Effective Against Human Monkeypox Virus in vitro at Nanomolar Concentrations[J]. Nature Microbiology, 2022, 7(12): 1951-1955. [36] KHALIL A, SAMARA A, O'BRIEN P, et al. Monkeypox and Pregnancy: What do Obstetricians Need to Know?[J]. Ultrasound Obstet Gynecol, 2022, 60(1): 22-27. [37] KARAN A, SHAH N, GARRIGUES JM, et al.Surveillance of Complicated Mpox Cases Unresponsive to Oral Tecovirimat in Los Angeles County, 2022[J]. J Infect Dis, 2024, 229(Suppl 2): 249-254. [38] DE CLERCQ E.Cidofovir in the Treatment of Poxvirus Infections[J]. Antiviral Res, 2002, 55(1): 1-13. [39] MAGEE WC, HOSTETLER KY, EVANS DH.Mechanism of Inhibition of Vaccinia Virus DNA Polymerase by Cidofovir Diphosphate[J]. Antimicrob Agents Chemother, 2005, 49: 3153-3162. [40] ALDERN KA, CIESLA SL, WINEGARDEN KL, HOSTETLER KY.Increased Antiviral Activity of 1-O-Hexadecyloxypropyl-[2-(14)C] Cidofovir in MRC-5 Human Lung Fibroblasts is Explained by Unique Cellular Uptake and Metabolism[J]. Mol Pharmacol, 2003, 63: 678-681. [41] HOSTETLER KY.Alkoxyalkyl Prodrugs of Acyclic Nucleoside Phosphonates Enhance Oral Antiviral Activity and Reduce toxicity: Current State of the Art[J]. Antiviral Res, 2009, 82(2): A84-A98. [42] LALEZARI JP, DREW WL, GLUTZER E, et al.(S)-1-[3-Hydroxy-2-(Phosphonylmethoxy)Propyl]Cytosine (Cidofovir): Results of a Phase I/II Study of a Novel Antiviral Nucleotide Analogue[J]. J Infect Dis, 1995, 171: 788-796. [43] CUNDY KC, LI ZH, LEE WA.Effect of Probenecid on the Distribution, Metabolism, and Excretion of Cidofovir in Rabbits[J]. Drug Metab Dispos, 1996, 24: 315-321. [44] QUENELLE DC, COLLINS DJ, KERN ER.Efficacy of Multiple-or Single-Dose Cidofovir Against Vaccinia and Cowpox Virus Infections in Mice[J]. Antimicrob Agents Chemother, 2003, 47(10): 3275-3280. [45] SMEE DF, GOWEN BB, WANDERSEE MK, et al.Differential Pathogenesis of Cowpox Virus Intranasal Infections in Mice Induced by Low and High Inoculum Volumes and Effects of Cidofovir Treatment[J]. Int J Antimicrob Agents, 2008, 31: 352-359. [46] WEI H, HUANG D, FORTMAN J, et al.Coadministration of Cidofovir and Smallpox Vaccine Reduced Vaccination Side Effects but Interfered with Vaccine-Elicited Immune Responses and Immunity to Monkeypox[J]. J Virol, 2009, 83: 1115-1125. [47] HUGGINS JW, MARTINEZ M, HARTMANN CJ, et al.17th International Conference on Antiviral Research in: Successful Cidofovir Treatment of Smallpox-Like Disease in Variola and Monkeypox Primate Models[J]. Antiviral Res, 2004, 62: A27-A90. [48] CHAN-TACK K, HARRINGTON P, BENSMAN T.Benefit-Risk Assessment for Brincidofovir for the Treatment of Smallpox: U.S. Food and Drug Administration's Evaluation[J]. Antiviral Res, 2021, 195: 105182. [49] QUINTANA-CASTANEDO L, TARIN-VICENTE EJ, CHILOECHES-FERNÁNDEZ C, et al. Recalcitrant Molluscum Contagiosum Successfully Treated with Intralesional Cidofovir in a Patient with HIV/AIDS[J]. Int J Dermatol, 2021, 60: 372-375. [50] KHANI E, AFSHARIRAD B, ENTEZARI-MALEKI T.Monkeypox Treatment: Current Evidence and Future Perspectives[J]. Journal of Medical Virology, 2023, 95(1): e28229. [51] GAO XU, PENG JE, LI XW, et al.Recent Research of Antiviral Drugs and Vaccines for Mpox[J]. Chinese Journal of Pharmacovigilance,2024, 21(1): 111-116. [52] PARKER S, TOUCHETTE E, OBERLE C, et al.Efficacy of Therapeutic Intervention with an Oral Ether-Lipid Analogue of Cidofovir (CMX001) in a Lethal Mousepox Model[J]. Antiviral Research, 2008, 77(1): 39-49. [53] HUTSON CL, KONDAS AV, MAULDIN MR, et al.Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model[J]. mSphere. 2021, 6(1): e0092. [54] CHITTICK G, MORRISON M, BRUNDAGE T, et al.Short-Term Clinical Safety Profile of Brincidofovir: A Favorable Benefit-Risk Proposition in the Treatment of Smallpox[J]. Antiviral Res, 2017, 143: 269-277. [55] RAO AK, SCHRODT CA, MINHAJ FS, et al.Interim Clinical Treatment Considerations for Severe Manifestations of Mpox- United States, February 2023[J]. Morb Mortal Wkly Rep, 2023, 72(9): 232-243. [56] KEMPE CH, BERGE TO, ENGLAND B.Hyperimmune Vaccinal Gamma Globulin, Source, Evaluation, and Use in Prophylaxis and Therapy[J]. Pediatrics, 1956, 18(2): 177-188. [57] HOPKINS RJ, KRAMER WG, BLACKWELDER WC, et al.Safety and Pharmacokinetic Evaluation of Intravenous Vaccinia Immune Globulin in Healthy Volunteers[J]. Clin Infect Dis, 2004, 39(6): 759-766. [58] WEBB E, RIGBY I, MICHELEN M, et al.Availability, Scope and Quality of Monkeypox Clinical Management Guidelines Globally: A Systematic Review[J]. BMJ Glob Health, 2022, 7(8): e009838. [59] CONTAG CA, MISCHE L, FONG I, et al.Treatment of Mpox with Suspected Tecovirimat Resistance in Immunocompromised Patient, United States, 2022[J]. Emerg Infect Dis, 2023, 29(12): 2520-2523. [60] THET AK, KELLY PJ, KASULE SN, et al.The Use of Vaccinia Immune Globulin in the Treatment of Severe Mpox, Virus Infection in Human Immunodeficiency Virus/AIDS[J]. Clin Infect Dis, 2023, 76(9): 1671-1673. [61] WITTEK R.Vaccinia Immune Globulin: Current Policies, Preparedness, and Product Safety and Efficacy[J]. Int J Infect Dis, 2006, 10(3): 193-201. [62] Centers for Disease Control and Prevention. Expanded Access IND Protocol: Use of Vaccinia Immune Globulin Intravenous (VIGIV, CNJ-016) for Treatment of Human Orthopoxvirus Infection in Adults and Children[EB/OL]. (2023-05-01)[2024-9-28]. https://www.cdc.gov/mpox/media/pdfs/2024/08/VIGIV-Protocol.pdf”. [63] ALTMANN S, BRANDT CR, MURPHY CJ, et al.Evaluation of Therapeutic Interventions for Vaccinia Virus Keratitis[J]. J Infect Dis, 2011, 203(5): 683-690. [64] FINE PE, JEZEK Z, GRAB B, et al.The Transmission Potential of Monkeypox Virus in Human Populations[J]. Int J Epidemiol, 1988, 17(3): 643-650. [65] AKTER F, HASAN TB, ALAM F, et al.Effect of Prior Immunisation with Smallpox Vaccine for Protection Against Human Mpox: A Systematic Review[J]. Rev Med Virol, 2023, 33(4): e2444. [66] LIU H, WANG W, ZHANG Y, et al.Global Perspectives on Smallpox Vaccine Against Monkeypox: a Comprehensive Meta-Analysis and Systematic Review of Effectiveness, Protection, Safety and Cross-Immunogenicity[J]. Emerg Microbes Infect, 2024, 13(1): 2387442. [67] MAYR A, MUNZ E.Veränderung Von Vaccinevirus Durch Dauerpassagen in Hühnerembryofibroblasten-Kulturen Changes in The Vaccinia Virus through Continuing Passages in Chick Embryo Fibroblast Cultures[J]. Zentralbl Bakteriol Orig, 1964, 195(1): 24-35. [68] MEYER H, SUTTER G, MAYR A.Mapping of Deletions in the Genome of the Highly Attenuated Vaccinia Virus MVA and Their Influence on Virulence[J]. J Gen Virol, 1991, 72( Pt 5): 1031-1038. [69] STITTELAAR KJ, KUIKEN T, DE SWART RL, et al.Safety of Modified Vaccinia Virus Ankara (MVA) in Immune-Suppressed Macaques[J]. Vaccine, 2001, 19(27): 3700-3709. [70] GRABENSTEIN JD, HACKER A.Vaccines Against Mpox: MVA-BN and LC16m8[J]. Expert Review of Vaccines, 2024, 23(1): 796-811. [71] EARL PL, AMERICO JL, WYATT LS, et al.Immunogenicity of a Highly Attenuated MVA Smallpox Vaccine and Protection Against Monkeypox[J]. Nature, 2004, 428(6979): 182-185. [72] FONTÁN-VELA M, HERNANDO V, OLMEDO C, et al. Effectiveness of Modified Vaccinia Ankara-Bavaria Nordic Vaccination in A Population at High Risk of Mpox: A Spanish Cohort Study[J]. Clin Infect Dis, 2024, 78(2): 476-483. [73] MAZZOTTA V, LEPRI AC, MATUSALI G, et al.Immunogenicity and Reactogenicity of Modified Vaccinia Ankara Pre-Exposure Vaccination Against Mpox According to Previous Smallpox Vaccine Exposure and HIV Infection: Prospective Cohort Study[J]. E Clinical Medicine, 2024, 68: 102420. [74] MONTANO M, SHAPIRO AE, WHITNEY BM, et al.Mpox in People with Human Immunodeficiency Virus: Predictors of Diagnosis, Outcomes, and Vaccine Effectiveness in A Multisite Cohort[J]. Clin Infect Dis, 2024, 78(2): 476-483. |
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