Yongjia Ji

Tuberculosis infection still places a great burden on HIV-infected individuals in China and other developing countries. Knowledge of the survival of HIV-infected patients with pulmonary tuberculosis (PTB) would provide important insights for the clinical management of this population, which remains to be well described in current China. HIV-infected patients with PTB admitted to Shanghai Public Health Clinical Center from January 2011 to December 2015 were retrospectively enrolled. In this cohort, the survival prognosis was estimated by the Kaplan-Meier method, while univariate and multivariate Cox proportional hazards models were used to determine the risk factors affecting mortality. After reviewing 4914 admitted patients with HIV infection, 359 PTB cases were identified. At the time of PTB diagnosis, the patients’ median CD4+ T cell count was 51 /mm3 (IQR: 23–116), and 27.30% of patients (98/359) were on combination antiretroviral therapy (cART). For the 333 cases included in the survival analysis, the overall mortality was 15.92% (53/333) during a median 27-month follow-up. The risk factors, including age older than 60 years (HR: 3.18; 95% CI: 1.66–6.10), complication with bacterial pneumonia (HR: 2.64; 95% CI: 1.30–5.35), diagnosis delay (HR: 2.60; 95% CI: 1.42–4.78), CD4+ T cell count less than 50/mm3 (HR: 2.38; 95% CI: 1.27–4.43) and pulmonary atelectasis (HR: 2.20; 95% CI: 1.05–4.60), might independently contribute to poor survival. Among patients without cART before anti-TB treatment, the later initiation of cART (more than 8 weeks after starting anti-TB treatment) was found to increase the mortality rate (OR: 4.33; 95% CI: 1.22–15.36), while the initiation of cART within 4–8 weeks after starting anti-TB treatment was associated with the fewest deaths (0/14). The subjects in this study conducted in the cART era were still characterized by depressed immunological competence and low rates of cART administration, revealing possible intervention targets for preventing TB reactivation in HIV-infected individuals under current circumstances. Furthermore, our study indicated that the timely diagnosis of PTB, prevention of secondary bacterial pneumonia by prophylactic management and optimization of the timing of cART initiation could have significant impacts on decreasing mortality among HIV/PTB co-infected populations. These findings deserve further prospective investigations to optimize the management of HIV/PTB-co-infected patients. NCT01344148 , Registered September 14, 2010.

随着HIV感染者接受高效抗逆转录病毒治疗后生存时间延长，HIV感染相关神经认知功能障碍（HAND）引起广泛关注。研究证据表明，HIV感染过程中各种细胞因子上调，导致血脑屏障通透性上升。受益于此，外周游离HIV病毒以及被HIV感染的免疫细胞（单核/巨噬细胞、T淋巴细胞）可加速穿越血脑屏障进入中枢神经系统，并导致中枢神经细胞感染HIV。此外，HIV感染的单核/巨噬细胞或T淋巴细胞进入中枢系统后还分泌多种促炎性细胞因子如TNF、IL-1ß等激活小胶质细胞以及星形胶质细胞。脑胶质细胞被激活后与血管周围外来巨噬细胞等免疫细胞共同作用分泌炎症介质，导致HIV感染相关中枢神经系统炎症以及神经功能损伤。HAND发病尽管受多种因素影响，但越来越多证据表明，HIV相关神经炎症反应是导致HIV感染者出现神经认知功能以及行为异常最重要的原因，未来应当围绕于此进行HAND相关治疗研究。本文就近年来HAND免疫发病机制相关研究进展做一综述。