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与 HIV 感染相关的结核病。

Tuberculosis Associated with HIV Infection.

机构信息

Johns Hopkins University School of Medicine, Division of Infectious Diseases, Baltimore, MD 21287.

Johns Hopkins University School of Medicine, Divisions of Clinical Pharmacology & Infectious Diseases, Center for Tuberculosis Research, Baltimore, MD 21287.

出版信息

Microbiol Spectr. 2017 Jan;5(1). doi: 10.1128/microbiolspec.TNMI7-0028-2016.

Abstract

Tuberculosis (TB) has recently surpassed HIV as the primary infectious disease killer worldwide, but the two diseases continue to display lethal synergy. The burden of TB is disproportionately borne by people living with HIV, particularly where HIV and poverty coexist. The impact of these diseases on one another is bidirectional, with HIV increasing risk of TB infection and disease progression and TB slowing CD4 recovery and increasing progression to AIDS and death among the HIV infected. Both antiretroviral therapy (ART) and latent TB infection (LTBI) treatment mitigate the impact of coinfection, and ART is now recommended for HIV-infected patients independent of CD4 count. LTBI screening should be performed for all HIV-positive people at the time of diagnosis, when their CD4 count rises above 200, and yearly if there is repeated exposure. Tuberculin skin tests (TSTs) may perform better with serial testing than interferon gamma release assays (IGRAs). Any patient with HIV and a TST induration of ≥5 mm should be evaluated for active TB disease and treated for LTBI if active disease is ruled out. Because HIV impairs multiple aspects of immune function, progressive HIV is associated with lower rates of cavitary pulmonary TB and higher rates of disseminated and extrapulmonary disease, so a high index of suspicion is important, and sputum should be obtained for evaluation even if chest radiographs are negative. TB diagnosis is similar in patients with and without TB, relying on smear, culture, and nucleic acid amplification tests, which are the initial tests of choice. TSTs and IGRAs should not be used in the evaluation of active TB disease since these tests are often negative with active disease. Though not always performed in resource-limited settings, drug susceptibility testing should be performed on all TB isolates from HIV-positive patients. Urine lipoarabinomannan testing may also be helpful in HIV-positive patients with disseminated disease. Treatment of TB in HIV-infected patients is similar to that of TB in HIV-negative patients except that daily therapy is required for all coinfected patients, vitamin B6 supplementation should be given to all coinfected patients receiving isoniazid to reduce peripheral neuropathy, and specific attention needs to be paid to drug-drug interactions between rifamycins and many classes of antiretrovirals. In patients requiring ART that contains ritonavir or cobicistat, this can be managed by the use of rifabutin at 150 mg daily in place of rifampin. For newly diagnosed coinfected patients, mortality is lower if treatment is provided in parallel, rather than serially, with treatment initiation within 2 weeks preferred for those with CD4 counts of <50 and within 8 to 12 weeks for those with higher CD4 counts. When TB immune reconstitution inflammatory syndrome occurs, patients can often be treated symptomatically with nonsteroidal anti-inflammatory drugs, but a minority will benefit from steroids. Generally, patients who do not have space-occupying lesions such as occurs in TB meningitis do not require cessation of therapy.

摘要

结核病(TB)最近已超过艾滋病毒成为全球主要传染病死因,但这两种疾病仍表现出致命的协同作用。结核病的负担不成比例地落在艾滋病毒感染者身上,特别是在艾滋病毒和贫困并存的地方。这两种疾病相互影响,艾滋病毒会增加感染和疾病进展的风险,而结核病则会减缓 CD4 恢复速度,并增加艾滋病毒感染者向艾滋病和死亡的进展。抗逆转录病毒疗法(ART)和潜伏性结核感染(LTBI)治疗都减轻了合并感染的影响,现在建议对所有 HIV 感染者进行 ART 治疗,而不考虑 CD4 计数。LTBI 筛查应在 HIV 阳性患者诊断时、CD4 计数升高至 200 以上时以及每年重复暴露时进行。结核菌素皮肤试验(TST)可能比干扰素γ释放试验(IGRA)更适合连续检测。任何 HIV 阳性且 TST 硬结≥5 毫米的患者都应评估是否有活动性结核病,并在排除活动性疾病后进行 LTBI 治疗。由于 HIV 会损害免疫功能的多个方面,因此进行性 HIV 与较低的空洞性肺结核发生率和较高的播散性和肺外疾病发生率相关,因此需要高度怀疑,即使胸部 X 线片为阴性,也应获取痰液进行评估。HIV 阳性和阴性患者的 TB 诊断相似,依靠涂片、培养和核酸扩增试验,这些都是首选的初始检测。TST 和 IGRAs 不应用于活动性结核病的评估,因为这些试验在活动性疾病中通常为阴性。尽管在资源有限的情况下并非总是进行,但应在所有 HIV 阳性患者的结核分离株上进行药物敏感性试验。尿液脂阿拉伯甘露聚糖检测也可能对有播散性疾病的 HIV 阳性患者有帮助。HIV 感染者的 TB 治疗与 HIV 阴性患者的治疗相似,只是所有合并感染者都需要每日治疗,所有接受异烟肼治疗的合并感染者都应给予维生素 B6 补充剂,以减少周围神经病,并且需要特别注意利福平类和许多类抗逆转录病毒药物之间的药物相互作用。对于需要包含利托那韦或考比司他的 ART 的患者,可以使用每日 150 毫克利福布汀代替利福平进行管理。对于新诊断的合并感染者,如果在 2 周内开始治疗,对于 CD4 计数<50 的患者,在 8 至 12 周内开始治疗,死亡率较低。当发生结核免疫重建炎症综合征时,患者通常可以用非甾体抗炎药对症治疗,但少数患者会从类固醇治疗中受益。一般来说,没有占位性病变的患者(例如发生结核性脑膜炎)不需要停止治疗。

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