尽管进行了抗逆转录病毒治疗，分枝杆菌结核特异性 CD4 T 细胞反应仍未完全恢复。

Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell responses despite antiretroviral therapy.

机构信息

The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

出版信息

J Infect. 2014 Apr;68(4):344-54. doi: 10.1016/j.jinf.2013.11.016. Epub 2013 Dec 8.

DOI:10.1016/j.jinf.2013.11.016

PMID:24325926

Abstract

OBJECTIVES

Despite antiretroviral therapy (ART), HIV-infected persons have increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10-specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks.

METHODS

HIV-infected, ART-naive Thai adults with CD4 T cell count ≤350 cells/μL starting ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T cells were detected by CD25/CD134 co-expression after stimulation with antigens.

RESULTS

Fifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186 cells/μL and plasma HIV-viral-load 4.9log10 copies/mL. Seventeen were TB-sensitised. At baseline, 25 had positive PPD and 15 had positive EC-Sp-CD4 response. CD4 T cell count <100 cells/μL was less (P = 0.005) and TB-sensitisation was more likely (P = 0.013) to be associated with positive baseline PPD-Sp-CD4 response. At wk4, the number of subjects with positive PPD-Sp-CD4 response rose to 35 (P = 0.021). Mean PPD-Sp-CD4 T cells increased at wk4 (P = 0.017) in patients not classified as TB-sensitised. The number of subjects with positive EC-Sp-CD4 response did not change significantly post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below baseline from wk12 (P = 0.010) onwards. EC-Sp-CD4 responses were undetectable in 3 out of 17 TB-sensitised patients.

CONCLUSIONS

Restoration of responses to TB-antigens was incomplete and inconsistent under the employed experimental conditions and may account for persistent increased risk of TB despite ART.

摘要

目的

尽管进行了抗逆转录病毒疗法（ART），但 HIV 感染者仍有发生活动性结核病（TB）的高风险。本研究在 96 周内检测了 PPD 和 ESAT-6 与 CFP-10 特异性-CD4（EC-Sp-CD4）应答。

方法

研究纳入了起始 ART 时 CD4 T 细胞计数≤350 个/μL 的 HIV 感染、ART 初治的泰国成年人，在基线、4、8、12、24、48 和 96 周时进行评估。通过抗原刺激后 CD25/CD134 共表达检测 PPD 和 EC-Sp-CD4 T 细胞。

结果

共纳入 50 名受试者，其中 39 名男性，中位年龄 32 岁，中位基线 CD4 T 细胞计数为 186 个/μL，血浆 HIV 病毒载量为 4.9log10 拷贝/mL。17 名受试者为 TB 致敏者。基线时，25 名受试者的 PPD 为阳性，15 名受试者的 EC-Sp-CD4 反应为阳性。CD4 T 细胞计数<100 个/μL（P=0.005）和 TB 致敏（P=0.013）更可能与基线 PPD-Sp-CD4 反应阳性相关。在第 4 周时，有 35 名（P=0.021）受试者的 PPD-Sp-CD4 反应转为阳性。在未被归类为 TB 致敏的患者中，第 4 周时 PPD-Sp-CD4 T 细胞数量增加（P=0.017）。在 ART 后，EC-Sp-CD4 反应的受试者数量没有明显变化。在 TB 致敏患者中，从第 12 周开始（P=0.010），EC-Sp-CD4 T 细胞均值下降至低于基线水平。在 17 名 TB 致敏患者中有 3 名患者的 EC-Sp-CD4 反应无法检测到。