BACKGROUND HIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutes Mycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated. METHOD A cross-sectional study was conducted to evaluate M. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing for M. tuberculosis infection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were performed after stimulation with M. tuberculosis antigens PPD and ESAT-6. RESULT The median frequency of PPD and ESAT-6 specific IFN-γ secreting cells was significantly higher in the HAART-treated patients as compared to HAART-naïve patients, p = 0.0021 and p = 0.0081 respectively. However, there was no significant difference in the median frequency of IL-2 secreting cells responding to PPD (p = 0.5981) and ESAT-6 (p = 0.3943) antigens between HAART-naïve and-treated groups. Both IFN-γ and IL-2 responses were independent of CD4+ T cell count regardless of the HAART status. Notably, the frequency of PPD and ESAT-6 specific IL-2 secreting cells was positively associated with CD4+ T cell proliferation while inversely correlated with duration of HAART, raising the possibility that M. tuberculosis-specific IL-2 response that promote the antigen-specific CD4+ T cell proliferation diminish with time on antiretroviral therapy in HIV/latent TB co-infected patients. CONCLUSION This study shows an increased M. tuberculosis-specific IFN-γ, but not IL-2, response in HIV/latent TB co-infected patients with long-term HAART, consistent with only partial immune restoration. Future studies should, therefore, be done to prospectively define the rate and extent to which functional immune responses to M. tuberculosis are restored after long-term HAART.

中文翻译：

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长期HAART治疗后，HIV /潜伏性结核合并感染患者对结核分枝杆菌抗原的IFN-γ反应增强，但对IL-2反应不明显。

背景技术具有潜伏性TB感染的HIV感染的个体发展为活动性TB的风险增加。在治疗的前12个月中，HAART大大降低了HIV感染患者中结核病的发生率，并重建了结核分枝杆菌（M. tuberculosis）特异性免疫反应。HAART一年后抗分枝杆菌免疫修复的耐久性尚待研究。方法进行了一项横断面研究，以评估与未接受HAART的患者相比，接受HAART至少1.5年至9年的HIV /潜伏性结核合并感染患者的结核分枝杆菌特异性功能免疫反应。通过结核菌素皮肤测试筛查了316例无活动性TB的HIV感染患者。结核感染和外周血单核细胞（PBMCs）是从61名HIV /潜伏性结核病合并感染患者（30例未经HAART治疗和31例经HAART治疗）中分离出来的。用结核分枝杆菌抗原PPD和ESAT-6刺激后，进行IFN-γ和IL-2 ELISPOT以及CFSE细胞增殖测定。结果与未接受HAART的患者相比，接受HAART的患者中PPD和ESAT-6特异性IFN-γ分泌细胞的中位频率显着更高，分别为p = 0.0021和p = 0.0081。但是，未接受HAART的组和接受过治疗的组之间，对PPD（p = 0.5981）和ESAT-6（p = 0.3943）抗原应答的IL-2分泌细胞的中位频率没有显着差异。无论HAART状态如何，IFN-γ和IL-2响应均与CD4 + T细胞计数无关。尤其，PPD和ESAT-6特异性IL-2分泌细胞的频率与CD4 + T细胞增殖呈正相关，而与HAART持续时间呈负相关，从而增加了结核分枝杆菌特异性IL-2应答促进抗原特异性CD4 +的可能性。 HIV /潜伏性结核病合并感染患者在抗逆转录病毒治疗中，T细胞增殖随着时间的推移而减少。结论这项研究表明，HIV /潜伏性结核病合并感染的长期HAART患者中，结核分枝杆菌特异性IFN-γ应答增加，但IL-2应答不增加，仅与部分免疫恢复相一致。因此，应进行进一步的研究以前瞻性地确定长期进行HAART后对结核分枝杆菌功能性免疫反应得以恢复的速度和程度。