人类免疫缺陷病毒感染/艾滋病合并结核病的诊治进展

doi:10.16150/j.1671-2870.2022.04.020

摘要/Abstract

摘要：

结核病是影响人类免疫缺陷病毒（human immunodeficiency virus,HIV）感染/艾滋病（acquired immune deficiency syndrome,AIDS）患者预后和生存质量的主要合并感染之一。HIV感染/AIDS合并结核病的临床特征与单纯结核病存在一定差异,其诊断和治疗更为困难。病原学诊断是目前临床上确诊结核病的主要依据,基于DNA和RNA技术的核酸检测方法,如利福平耐药结核分枝杆菌实时荧光定量核酸扩增检测技术（Xpert Mycobacterium tuberculosis/Rifampicin,Xpert MTB/RIF）及其新一代技术Xpert MTB/RIF Ultra等,因其高灵敏度和特异度已越来越多地被用于HIV感染/AIDS患者中结核病的早期诊断。当前,许多研究希望通过多组学研究发现新的诊断标志物,虽然目前转录组、蛋白组的研究已经发现了某些具有潜在价值的生物标志物,但其临床实用价值尚待进一步的研究和证实。HIV感染/AIDS合并结核病的治疗包括抗结核分枝杆菌（Mycobacterium tuberculosis,MTB）治疗和抗逆转录病毒治疗（anti-retroviral therapy,ART）两方面。原则上,其治疗与单纯感染者的治疗相同,但由于HIV与MTB 2种病原体间的相互影响以及治疗药物间存在的相互作用,合并感染患者的治疗更为复杂。共感染诊治的复杂性导致其治疗的结局仍有待进一步改善。

关键词: 人类免疫缺陷病毒感染/艾滋病, 结核病, 发病机制, 诊断, 治疗

Abstract:

Tuberculosis is one of the major co-infections that affect the prognosis and quality of life of HIV infection/ AIDS patients. The clinical characteristics of HIV infection/AIDS patients combined with tuberculosis are different from those of patients with tuberculosis alone, and its diagnosis and treatment are more difficult. Etiological diagnosis is the main basis for clinical diagnosis of tuberculosis, and nucleic acid detection methods based on DNA and RNA technology, such as Xpert MTB/RIF and Xpert MTB/RIF Ultra, have been used for early diagnosis for HIV infetion/AIDS patients combined with tuberculosis due to their high sensitivity and specificity. At present, many studies hope to find new diagnostic markers through multi-omics research to help to diagnose tuberculosis earlier and faster in patients. Although there are some biomarkers with potential value in the research of transcriptome and proteome, the practical value needs further research and confirmation. The treatments for patients with co-infection include anti-MTB therapy and antiretroviral therapy (ART). In principle, the treatment of co-infection is the same as that of single pathogen infection. However, due to the complex interactions between the two pathogens and among the therapeutic medicines, the treatment of patients with co-infection is more complex. The complexity of the diagnosis and treatment of co-infection leads to the treatment outcome still needing to be further improved. It is particularly important for us to further study the mechanism and impact of HIV infection/MTB interaction and to explore more optimized and accessible clinical diagnosis methods and treatment regimens in future research.

Key words: Human immunodeficiency virus infection/acquired immune deficiency syndrome, Tuberculosis, Pathogenesis, Diagnosis, Treatment

中图分类号:

R512.91

陈宏, 沈银忠. 人类免疫缺陷病毒感染/艾滋病合并结核病的诊治进展[J]. 诊断学理论与实践, 2022, 21(04): 530-534.

CHEN Hong, SHEN Yinzhong. Progress in diagnosis and treatment of human immunodeficiency virus infection/acquired immune deficiency syndrome complicated with tuberculosis[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 530-534.

参考文献 29

[1]	Key facts and latest estimates on the global HIV epide-mic-2021[R/OL]. [2022-09-19]. https://cdn.who.int/media/docs/default-source/hq-hiv-hepatitis-and-stis-library/key-facts-hiv-2021-262022.7.
[2]	World Health Organization. Global tuberculosis report 2021[R/OL]. 2021-10-14[2022-4-22]. https://www.who.int/publications/i/item/9789240037021。
[3]	疾病预防控制局. 2021年全国法定传染病疫情概况[R/OL]. 中华人民共和国国家卫生健康委员会.2022-04-22[2022-04-22]. http://www.nhc.gov.cn/jkj/s3578/202204/4fd88a291d914abf8f7a91f6333567e1.shtml.
	Bureau of Disease Control and Prevention of China. Overview of national notifiable infectious diseases in 2021[R/OL]. State Health Commission of the People′s Republic of China.2022-04-22[2022-04-22]. http://http://www.nhc.gov.cn/jkj/s3578/202204/4fd88a291d914abf8f7a91f6333567e1.shtml.
[4]	刘爱梅. 440例艾滋病合并结核病临床感染状况的分析[J]. 中国医科大学学报, 2010, 39(1):34-36.
	Liu AM. A Clinical Analysis of 440 Acquired Immunodeficiency Syndrome Patients Infected with Mycobacterium Tuberculosis[J]. J China Med Univ, 2010, 39(1):34-36.
[5]	曾朗, 刘嵩. 艾滋病并发肺结核病多层螺旋CT表现特点评价[J]. 中国急救复苏与灾害医学杂志, 2020, 15(z1):7-9.
	Zeng L, Liu S. Evaluation of MSCT features in PATIENTS with AIDS complicated with tuberculosis[J]. China J Emerg Resusc Disaster Med, 2020, 15(z1):7-9.
[6]	孙燕, 杨宣, 马永红, 等. 艾滋病合并肺结核病的影像学特点与CD4细胞计数的相关性[C]. 第四届全国艾滋病临床影像学术会议暨第二届全国感染及传染影像学最新进展学术会议, 2011.
	Yang X, Ma YH, et al. Correlation between ima-ging characteristics of AIDS complicated with pulmonary tuberculosis and CD4 cell count[C]. The Fourth National Conference on Clinical Imaging of AIDS and the Second National Conference on the Latest Progress in Imaging of Infection, 2011.
[7]	中国性病艾滋病防治协会HIV合并结核病专业委员会. 人类免疫缺陷病毒感染/艾滋病合并结核分枝杆菌感染诊治专家共识[J]. 中华传染病杂志, 2022, 40(1):6-19.
	China STD AIDS Prevention Association, Committee on HIV and tuberculosis. Expert consensus on diagnosis and treatment of Mycobacterium tuberculosis infection in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome[J]. Chin J Infect Dis, 2022, 40(1):6-19.
[8]	Steingart KR, Schiller I, Horne DJ, et al. MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults[J]. Cochrane Database Syst Rev, 2014, 2014(1):CD009593.
[9]	Theron G, Zijenah L, Chanda D, et al. Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial[J]. Lancet, 2014, 383(9915):424-435. doi: 10.1016/S0140-6736(13)62073-5 pmid: 24176144
[10]	Kohli M, Schiller I, Dendukuri N, et al. XpertMTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance[J]. Cochrane Database Syst Rev, 2018, 8(8):CD012768.
[11]	Theron G, Peter J, Calligaro G, et al. Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments[J]. Sci Rep, 2014, 4:5658. doi: 10.1038/srep05658 pmid: 25014250
[12]	Bahr NC, Nuwagira E, Evans EE, et al. Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study[J]. Lancet Infect Dis, 2018, 18(1):68-75. doi: S1473-3099(17)30474-7 pmid: 28919338
[13]	Sweeney TE, Braviak L, Tato CM, et al. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis[J]. Lancet Respir Med, 2016, 4(3):213-224. doi: 10.1016/S2213-2600(16)00048-5 pmid: 26907218
[14]	Kaforou M, Wright VJ, Oni T, et al. Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study[J]. PLoS Med, 2013, 10(10):e1001538.
[15]	Anderson ST, Kaforou M, Brent AJ, et al. Diagnosis of childhood tuberculosis and host RNA expression in Africa[J]. N Engl J Med, 2014, 370(18):1712-1723. doi: 10.1056/NEJMoa1303657 URL
[16]	Shen Y, Xun J, Song W, et al. Discovery of Potential Plasma Biomarkers for Tuberculosis in HIV-Infected Patients by Data-Independent Acquisition-Based Quantitative Proteomics[J]. Infect Drug Resist, 2020, 13:1185-1196. doi: 10.2147/IDR.S245460 pmid: 32425558
[17]	Chen C, Yan T, Liu L, et al. Identification of a Novel Serum Biomarker for Tuberculosis Infection in Chinese HIV Patients by iTRAQ-Based Quantitative Proteomics[J]. Front Microbiol, 2018, 9:330. doi: 10.3389/fmicb.2018.00330 pmid: 29535695
[18]	Singer SN, Ndumnego OC, Kim RS, et al. Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV[J]. EBioMedicine, 2022, 75:103787. doi: 10.1016/j.ebiom.2021.103787 URL
[19]	Dorman SE, Nahid P, Kurbatova EV, et al. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis[J]. N Engl J Med, 2021, 384(18):1705-1718. doi: 10.1056/NEJMoa2033400 URL
[20]	Nglazi MD, Bekker LG, Wood R, et al. The impact of HIV status and antiretroviral treatment on TB treatment outcomes of new tuberculosis patients attending co-located TB and ART services in South Africa: a retrospective cohort study[J]. BMC Infect Dis, 2015, 15:536. doi: 10.1186/s12879-015-1275-3 pmid: 26584607
[21]	Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy[J]. N Engl J Med, 2010, 362(8):697-706. doi: 10.1056/NEJMoa0905848 URL
[22]	Abdool Karim SS, Naidoo K, Grobler A, et al. Integration of antiretroviral therapy with tuberculosis treatment[J]. N Engl J Med, 2011, 365(16):1492-1501. doi: 10.1056/NEJMoa1014181 URL
[23]	Blanc FX, Sok T, Laureillard D, et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis[J]. N Engl J Med, 2011, 365(16):1471-1481. doi: 10.1056/NEJMoa1013911 URL
[24]	Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis[J]. N Engl J Med, 2011, 365(16):1482-1491. doi: 10.1056/NEJMoa1013607 URL
[25]	Smith JP, Gandhi NR, Shah NS, et al. The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events[J]. J Acquir Immune Defic Syndr, 2020, 83(1):47-55. doi: 10.1097/QAI.0000000000002190 pmid: 31809360
[26]	Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach[EB/OL]. Geneva: World Health Organization. 2021[2022-04-22]. http://apps.who.int/iris.
[27]	Padmapriyadarsini C, Bhavani PK, Tang A, et al. Early changes in hepatic function among HIV-tuberculosis patients treated with nevirapine or efavirenz along with rifampin-based anti-tuberculosis therapy[J]. Int J Infect Dis, 2013, 17(12):e1154-e1159. doi: 10.1016/j.ijid.2013.08.006 URL
[28]	Ravimohan S, Auld SC, Maenetje P, et al. Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis[J]. Clin Infect Dis, 2020, 70(9):1845-1854. doi: 10.1093/cid/ciz560 pmid: 31242296
[29]	Modongo C, Wang Q, Dima M, et al. Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana[J]. J Acquir Immune Defic Syndr, 2019, 82(2):111-115. doi: 10.1097/QAI.0000000000002126 pmid: 31335593