da Silva Tatiana P, Giacoia-Gripp Carmem B W, Schmaltz Carolina A, Sant Anna Flavia M, Rolla Valeria, Morgado Mariza G
Laboratory of AIDS and Immunology Molecular, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
PLoS One. 2013 Jun 19;8(6):e66095. doi: 10.1371/journal.pone.0066095. Print 2013.
The profile of immune activation markers in tuberculosis and HIV-infected patients is already known. The impact of simultaneous infections on the immune parameters is still not fully explored.
We conducted a prospective study to estimate trajectories of activated T cell subsets and the profile of anti- and pro-inflammatory cytokines in a group of HIV-TB individuals, previously naïve for HAART, recruited from a randomized clinical trial during TB treatment and first antiretroviral therapy with efavirenz. Patients were evaluated according to the immunosuppression levels at baseline as group 1 (CD4<200 cells/mm(3)) and group 2 (CD4>200 cells/mm(3)). These parameters were measured at the time of HAART initiation (started about 30 days after the onset of TB treatment) and at the follow-up visits after 30, 60, 90 and 180 days. Trajectories were estimated using least squares estimates of the coefficients of a restricted cubic spline function in time after adjusting for subject effects, bootstrapping it 500 times.
Increase of CD4 T cell counts and suppression of HIV viral load were observed for all patients under HAART and TB treatment. Descendent trajectories were observed for the activated CD8(+)/CD38(+) and CD3(+)/HLA-DR(+) T cell subsets, and for plasma concentration of gamma- interferon (IFN-γ). Except for TNF-α and IL-2 discrete variations were observed for the other cytokines. Differences in the trajectories of these parameters were observed for groups 1 and 2. Higher values of IFN-γ, IL-2, IL-6 and IL-10 were observed for group 1 from the baseline to two months after treatment initiation, whereas reduced levels of TNF-α were observed for this group between 60 and 120 days of HAART.
Independent of the immunosuppression profile at baseline, HIV-TB patients under HAART were able to recover the CD4(+) T cell counts, and control viral replication and immune activation parameters over time.
结核病患者和艾滋病毒感染患者体内免疫激活标志物的情况已为人所知。同时感染对免疫参数的影响仍未得到充分研究。
我们开展了一项前瞻性研究，以评估一组之前未接受过高效抗逆转录病毒治疗（HAART）的艾滋病毒合并结核病患者在结核病治疗期间及首次使用依非韦伦进行抗逆转录病毒治疗时，活化T细胞亚群的变化轨迹以及抗炎和促炎细胞因子的情况。这些患者从一项随机临床试验中招募而来，根据基线时的免疫抑制水平分为1组（CD4<200个细胞/mm³）和2组（CD4>200个细胞/mm³）。在开始HAART时（大约在结核病治疗开始后30天）以及30、60、90和180天后的随访时测量这些参数。在调整个体效应后，使用受限立方样条函数系数的最小二乘估计来估计变化轨迹，并进行500次自抽样。
在接受HAART和结核病治疗的所有患者中，均观察到CD4 T细胞计数增加以及艾滋病毒病毒载量受到抑制。活化的CD8(+)/CD38(+)和CD3(+)/HLA-DR(+) T细胞亚群以及γ-干扰素（IFN-γ）的血浆浓度呈下降趋势。除肿瘤坏死因子-α（TNF-α）和白细胞介素-2（IL-2）外，其他细胞因子均观察到离散变化。1组和2组在这些参数的变化轨迹上存在差异。从基线到治疗开始后两个月，1组的IFN-γ、IL-2、IL-6和IL-10值较高，而在HAART治疗60至120天期间，该组的TNF-α水平降低。
无论基线时的免疫抑制情况如何，接受HAART治疗的艾滋病毒合并结核病患者能够随着时间推移恢复CD4(+) T细胞计数，并控制病毒复制和免疫激活参数。
