The Effect of Early Initiation of Antiretroviral Therapy in TB/HIV-Coinfected Patients: A Systematic Review and Meta-Analysis.
The Effect of Early Initiation of Antiretroviral Therapy in TB/HIV-Coinfected Patients: A Systematic Review and Meta-Analysis.
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DOI：
10.1177/2325957415599210
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发表时间：
2015-11-01
影响因子：
--
通讯作者：
Deribew, Amare
中科院分区：
文献类型：
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作者：
Abay, Solomon M;Deribe, Kebede;Deribew, Amare
背景：对于结核（TB）和hiv合并感染患者早期开始抗逆转录病毒治疗（ART）的重要性存在争议。我们进行了一项系统回顾和荟萃分析，以评估早期开始抗逆转录病毒治疗（结核病治疗后2-4周内）对结核病/ hiv合并感染患者的几种治疗结果的影响。方法：系统检索PubMed、Embase、谷歌Scholar、Science Direct、Medscape和Cochrane图书馆的临床试验。包括在最后检索日期（2015年3月31日）之前以任何语言发表的临床试验。使用Cochrane图书馆的标准评估研究的质量。采用异质性检验来评估研究结果之间的差异。对于每个研究结果，计算具有95%置信区间（CI）的风险比（RR）作为干预效果的度量。采用固定效应模型，采用Mantel-Haenszel方法估计RR。结果：meta分析共纳入6项试验的2272名研究参与者。结核病治疗期间早期开始抗逆转录病毒治疗与全因死亡率降低（RR = 0.78; 95% CI = 0.63-0.98）、结核病相关免疫重建炎症综合征（TB- iris; RR = 2.19; 95% CI = 1.77- 2.70）和结核病- iris相关死亡率增加（RR = 6.94; 95% CI = 1.26-38.22）相关。然而，开始抗逆转录病毒治疗的时间与结核病治愈率（RR = 0.99; 95% CI = 0.81-1.07）、药物毒性率（RR = 1.00; 95% CI = 0.93-1.08）、与药物毒性相关的死亡（RR = 0.40; 95% CI = 0.14- 1.16）、低病毒载量率（小于400拷贝/mL； RR = 1.00; 95% CI = 0.96-1.04）和新发艾滋病定义疾病率（RR = 0.84; 95% CI = 0.60-1.18）无关。在不同的试验中，研究参与者的早期ART组的免疫应答与晚期ART组相比显示出更大或相同的应答。结论：本系统综述提供了确凿证据，证明早期开始抗逆转录病毒治疗可降低全因死亡率。然而，这项研究也证实了结核病- iris的高发病率和与之相关的死亡率。需要开展业务和实施研究，以保持早期开始抗逆转录病毒治疗的益处和对结核病综合免疫系统的适当管理。建议对肺外和耐多药结核病患者进行ART治疗时机的研究。
BACKGROUND: The importance of early initiation of antiretroviral therapy (ART) for tuberculosis (TB) and HIV-coinfected patients is controversial. We conducted a systematic review and meta-analysis to assess the effect of early initiation of ART (within 2-4 weeks of TB treatment) on several treatment outcomes among TB/HIV-coinfected patients.METHOD: A systematic search of clinical trials was performed in PubMed, Embase, Google Scholar, Science Direct, Medscape, and the Cochrane library. Clinical trials which were published in any language before the last date of search (March 31, 2015) were included. The qualities of the studies were assessed using criteria from the Cochrane Library. Heterogeneity test was conducted to assess the variations among study outcomes. For each study outcome, the risk ratio (RR) with 95% confidence interval (CI) was calculated as a measure of intervention effect. The Mantel-Haenszel method was used to estimate the RR using a fixed-effects model.FINDINGS: A total of 2272 study participants from 6 trials were included in the meta-analysis. Early ART initiation during TB treatment was associated with reduced all-cause mortality (RR = 0.78; 95% CI = 0.63-0.98) and increased rate of TB-associated immune reconstitution inflammatory syndrome (TB-IRIS; RR = 2.19; 95% CI = 1.77- 2.70) and death related to TB-IRIS (RR = 6.94; 95% CI = 1.26-38.22). However, the time of ART initiation has no association with TB cure rate (RR = 0.99; 95% CI = 0.81-1.07), rate of drug toxicity (RR = 1.00; 95% CI = 0.93-1.08), death associated with drug toxicity (RR = 0.40; 95% CI = 0.14- 1.16), rate of low viral load (less than 400 copies/mL; RR = 1.00; 95% CI = 0.96-1.04), and rate of new AIDS-defining illness (RR = 0.84; 95% CI = 0.60-1.18). Immunological response in early ART arms of study participant in different trials showed a greater or equal response compared with late ART arms.CONCLUSION: This systematic review presents conclusive evidence on the reduction of all-cause mortality as a result of early initiation of ART. However, this study also confirms the high rate of TB-IRIS and death associated with it. Operational and implementation research are required to maintain the benefit of early ART initiation and proper management of TB-IRIS. Studies on the timing of ART in extrapulmonary and multidrug-resistant TB are recommended.