Incidence and predictors of tuberculosis among HIV-infected adults after initiation of antiretroviral therapy in Nigeria, 2004-2012

Background
Nigeria had the most AIDS-related deaths worldwide in 2014 (170,000), and 46% were associated with tuberculosis (TB). Although treatment of people living with HIV (PLHIV) with antiretroviral therapy (ART) reduces TB-associated morbidity and mortality, incident TB can occur while on ART. We estimated incidence and characterized factors associated with TB after ART initiation in Nigeria.
Methods
We analyzed retrospective cohort data from a nationally representative sample of adult patients on ART. Data were abstracted from 3,496 patient records, and analyses were weighted and controlled for a complex survey design. We performed domain analyses on patients without documented TB disease and used a Cox proportional hazard model to assess factors associated with TB incidence after ART.
Results
At ART initiation, 3,350 patients (95.8%) were not receiving TB treatment. TB incidence after ART initiation was 0.57 per 100 person-years, and significantly higher for patients with CD4<50/μL (adjusted hazard ratio [AHR]: 4.2, 95% confidence interval [CI]: 1.4–12.7) compared with CD4≥200/μL. Patients with suspected but untreated TB at ART initiation and those with a history of prior TB were more likely to develop incident TB (AHR: 12.2, 95% CI: 4.5–33.5 and AHR: 17.6, 95% CI: 3.5–87.9, respectively).
Conclusion
Incidence of TB among PLHIV after ART initiation was low, and predicted by advanced HIV, prior TB, and suspected but untreated TB. Study results suggest a need for improved TB screening and diagnosis, particularly among high-risk PLHIV initiating ART, and reinforce the benefit of early ART and other TB prevention efforts.

研究背景
尼日利亚在2014年的艾滋病相关死亡人数位居全球首位（170000例），其中46%与结核病（tuberculosis, TB）相关。尽管针对艾滋病病毒感染者（people living with HIV, PLHIV）实施抗逆转录病毒治疗（antiretroviral therapy, ART）可降低结核病相关的发病率与死亡率，但患者在接受ART治疗期间仍可能发生新发结核病。本研究针对尼日利亚开展分析，旨在评估ART启动后结核病的发病情况，并明确与之相关的影响因素。

研究方法
本研究对全国代表性样本中接受ART治疗的成年患者的回顾性队列数据进行分析。研究共提取3496份患者病历，并针对复杂调查设计进行加权与混杂控制。我们针对无明确结核病病史记录的患者开展亚组分析，并采用Cox比例风险模型（Cox proportional hazard model）评估ART启动后结核病发病的相关影响因素。

研究结果
在ART启动时，共计3350例患者（95.8%）未接受结核病治疗。ART启动后结核病发病率为0.57例/100人年；与CD4≥200/μL的患者相比，CD4<50/μL的患者结核病发病率显著更高（校正风险比（adjusted hazard ratio, AHR）：4.2，95%置信区间（confidence interval, CI）：1.4~12.7）。ART启动时疑似结核病但未接受治疗的患者，以及既往有结核病病史的患者，发生新发结核病的风险更高（校正风险比分别为12.2、17.6，95%置信区间分别为4.5~33.5、3.5~87.9）。

研究结论
艾滋病病毒感染者在接受ART治疗后新发结核病的发病率较低，且可通过晚期HIV感染、既往结核病病史以及ART启动时疑似未治结核病进行预测。本研究结果提示，需加强结核病筛查与诊断工作，尤其是针对启动ART治疗的高风险艾滋病病毒感染者群体，同时也进一步证实了早期ART治疗及其他结核病预防措施的临床价值。