Rationale: Performance of blood transcriptomic tuberculosis (TB) signatures in longitudinal studies and effects of TB-preventive therapy and coinfection with HIV or respiratory organisms on transcriptomic signatures has not been systematically studied. Objectives: We evaluated longitudinal kinetics of an 11-gene blood transcriptomic TB signature, RISK11, and effects of TB-preventive therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. Methods: RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort, or a longitudinal study in people living with HIV (PLHIV). HIV-uninfected RISK11+ participants were randomized to TPT or no TPT; RISK11- participants received no TPT. PLHIV received standard-of-care antiretroviral therapy and TPT. In the cross-sectional respiratory organisms cohort, viruses and bacteria in nasopharyngeal and oropharyngeal swabs were quantified by real-time quantitative PCR. Measurements and Main Results: RISK11+ status was transient in most of the 128 HIV-negative participants with longitudinal samples; more than 70% of RISK11+ participants reverted to RISK11- by 3 months, irrespective of TPT. By comparison, reversion from a RISK11+ state was less common in 645 PLHIV (42.1%). Non-HIV viral and nontuberculous bacterial organisms were detected in 7.2% and 38.9% of the 1,000 respiratory organisms cohort participants, respectively, and among those investigated for TB, 3.8% had prevalent disease. Median RISK11 scores (%) were higher in participants with viral organisms alone (46.7%), viral and bacterial organisms (42.8%), or prevalent TB (85.7%) than those with bacterial organisms other than TB (13.4%) or no organisms (14.2%). RISK11 could not discriminate between prevalent TB and viral organisms. Conclusions: Positive RISK11 signature status is often transient, possibly due to intercurrent viral infection, highlighting potentially important challenges for implementation of these biomarkers as new tools for TB control.

中文翻译：

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结核病血液转录组特征的纵向动力学。

基本原理：血液转录组结核病 (TB) 特征在纵向研究中的表现以及结核病预防治疗和 HIV 或呼吸道生物合并感染对转录组特征的影响尚未得到系统研究。目的：我们在未感染 HIV 和感染 HIV 的个体中评估了 11 基因血液转录组 TB 特征、RISK11 的纵向动力学，以及 TB 预防治疗 (TPT) 和呼吸道微生物对 RISK11 特征评分的影响。方法：在未感染 HIV 的成人中进行的 RISK11 指导的 TPT 纵向研究、横断面呼吸道生物队列或 HIV 感染者 (PLHIV) 的纵向研究中测量了 RISK11。未感染 HIV 的 RISK11+ 参与者被随机分配到 TPT 或无 TPT；RISK11-参与者没有收到 TPT。PLHIV 接受了标准护理抗逆转录病毒治疗和 TPT。在横断面呼吸道生物队列中，通过实时定量 PCR 对鼻咽和口咽拭子中的病毒和细菌进行了定量。测量和主要结果：在 128 名纵向样本的 HIV 阴性参与者中，大多数 RISK11+ 状态是短暂的；超过 70% 的 RISK11+ 参与者在 3 个月内恢复到 RISK11-，无论 TPT 是多少。相比之下，从 RISK11+ 状态恢复在 645 名 PLHIV 中不太常见（42.1%）。在 1,000 名呼吸道微生物队列参与者中，分别有 7.2% 和 38.9% 检测到非 HIV 病毒和非结核性细菌微生物，在接受结核病调查的参与者中，3.8% 患有流行病。仅病毒生物的参与者（46.7%）的中位 RISK11 评分（%）较高，病毒和细菌生物体（42.8%），或流行的结核病（85.7%）高于那些有除结核病以外的细菌生物体（13.4%）或没有生物体（14.2%）的人。RISK11 无法区分流行的结核病和病毒生物。结论：阳性 RISK11 特征状态通常是短暂的，可能是由于并发病毒感染，突出了将这些生物标志物作为结核病控制的新工具实施的潜在重要挑战。