Bushra Abdulhalik Workicho, Zeynudin Ahmed, Dejene Tariku, Wolde Mirkuzie, Sudhakar Morankar
1. Lecturer, Department of Epidemiology, College of Public Health and Medical Sciences, The Ethiopian Malaria Alert Centre: a collaborating centre of the Joanna Briggs Institute, Email:
JBI Libr Syst Rev. 2012;10(55):3561-3595. doi: 10.11124/01938924-201210550-00001.
Tuberculosis is one of the most frequent causes of death among adults despite being nearly 100% curable in the developing world. The lifetime risk of tuberculosis in immune competent persons is 5% to 10%, but in HIV positive individuals, there is a 5% to 15% annual risk of developing active tuberculosis disease and there appears to be little research addressing HIV and tuberculosis co-infection.
To synthesise the best available evidence on risk factors for developing tuberculosis after highly active antiretroviral treatment initiation among HIV patients INCLUSION CRITERIA: HIV patients who had initiated highly active antiretroviral treatment and were above 15 years of age.Risk factors for developing active tuberculosis among HIV patients after initiation of highly active antiretroviral treatment.Analytical epidemiological study designs were included in the review.The studies considered in this review included socio-demographic and clinical variables as risk factors for developing tuberculosis after HAART initiation such as, but not limited to: baseline CD4 count, HAART type, WHO clinical stage of HIV, previous history of TB and gender.
English language articles published between January 1997 and December 2011 were searched using a comprehensive search strategy.
Conducted, using the Joanna Briggs Institute critical appraisal tools.
Carried out, using the Joanna Briggs Institute data extraction tool.
Meta- analysis was conducted using random effects model with Rev Man 5 software.
Five cohort studies were included in the review. The risk of developing active tuberculosis after initiating highly active antiretroviral treatment was found to be 2.14 times higher in subjects with a baseline CD4+ cell count ≥ 200 than their counterparts with a 95% CI from 1.52 to 3.02 and this effect was statistically significant, p<0.0001. The overall effect of gender on development of post highly active antiretroviral treatment tuberculosis was found to be not significant, p=0.64. The meta analysis for prior TB history as a risk factor favoured those who didn't have prior tuberculosis history to have 1.24 times higher risk than their counter parts even if it is not found to be statistically significant, p=0.56. There was no difference identified in the risk of developing post highly active antiretroviral treatment tuberculosis among patients taking protease inhibitor based treatment regimens and those taking non nucleoside reverse transcriptase inhibitor based treatment regimen. The last variable considered as a risk factor for post highly active antiretroviral treatment tuberculosis was the WHO's clinical stages for HIV and the risk was found to be 1.77 times higher among those who were at stage 1 or 2 during enrolment than their counterparts but this risk is not statistically significant, p=0.44.
Having no prior tuberculosis history, female gender and WHO clinical stage of HIV at enrolment were found to be a risk but their relation with post highly active antiretroviral treatment tuberculosis was not statistically significant. The meta-analysis also did not identify any difference among the groups taking protease inhibiter based and non nucleoside reverse transcriptase inhibiters (NNRTI) based treatments in relation to post highly active antiretroviral treatment tuberculosis. But, the analysis revealed that there exists a statistically significant risk for developing post highly active antiretroviral treatment tuberculosis among individuals having a baseline CD4+ cell count ≥ 200 being found to be at higher risk.Unlike other HIV-associated opportunistic infections, tuberculosis may occur at relatively high CD4+ cell counts. Patients with no prior tuberculosis history and at WHO clinical stage 1 or 2 of HIV may also be at risk of developing post-HAART TB and need to be investigated thoroughly.Further longitudinal studies covering all other possible risk factors such as genetic and behavioral factors need to be carried out to produce comprehensive data.
尽管在发展中国家结核病几乎100%可治愈，但它仍是成年人中最常见的死亡原因之一。免疫功能正常者一生中患结核病的风险为5%至10%，但在HIV阳性个体中，每年有5%至15%的风险发展为活动性结核病，而且针对HIV与结核病合并感染的研究似乎很少。
综合现有最佳证据，探讨HIV患者开始高效抗逆转录病毒治疗后发生结核病的危险因素。
开始高效抗逆转录病毒治疗且年龄在15岁以上的HIV患者。HIV患者开始高效抗逆转录病毒治疗后发生活动性结核病的危险因素。本综述纳入了分析性流行病学研究设计。本综述考虑的研究包括社会人口统计学和临床变量，如但不限于：基线CD4细胞计数、高效抗逆转录病毒治疗类型、HIV的世界卫生组织临床分期、既往结核病史和性别，作为开始高效抗逆转录病毒治疗后发生结核病的危险因素。
使用全面检索策略检索1997年1月至2011年12月发表的英文文章。
使用乔安娜·布里格斯研究所的批判性评价工具进行。
使用乔安娜·布里格斯研究所的数据提取工具进行。
使用Rev Man 5软件的随机效应模型进行荟萃分析。
本综述纳入了五项队列研究。发现基线CD4+细胞计数≥200的受试者开始高效抗逆转录病毒治疗后发生活动性结核病的风险比基线CD4+细胞计数＜200的受试者高2.14倍，95%置信区间为1.52至3.02，且该效应具有统计学意义，p＜0.0001。性别对高效抗逆转录病毒治疗后结核病发生的总体影响不显著，p = 0.64。作为危险因素的既往结核病史的荟萃分析显示，既往无结核病史者发生结核病的风险比有结核病史者高1.24倍，尽管未发现具有统计学意义，p = 0.56。接受基于蛋白酶抑制剂的治疗方案的患者与接受基于非核苷类逆转录酶抑制剂的治疗方案的患者在高效抗逆转录病毒治疗后发生结核病的风险上未发现差异。最后一个被视为高效抗逆转录病毒治疗后结核病危险因素的变量是HIV的世界卫生组织临床分期，发现入组时处于1期或2期的患者发生结核病的风险比其他患者高1.77倍，但该风险无统计学意义，p = 0.44。
既往无结核病史、女性以及入组时HIV的世界卫生组织临床分期被发现是危险因素，但它们与高效抗逆转录病毒治疗后结核病的关系无统计学意义。荟萃分析也未发现接受基于蛋白酶抑制剂的治疗和接受基于非核苷类逆转录酶抑制剂（NNRTI）的治疗的两组患者在高效抗逆转录病毒治疗后结核病方面存在差异。但是，分析显示基线CD4+细胞计数≥200的个体在高效抗逆转录病毒治疗后发生结核病存在统计学意义的风险，且风险更高。与其他HIV相关机会性感染不同，结核病可能在CD4+细胞计数相对较高时发生。既往无结核病史且处于HIV世界卫生组织临床分期1期或2期的患者也可能有高效抗逆转录病毒治疗后发生结核病的风险，需要进行全面调查。需要开展进一步的纵向研究，涵盖所有其他可能的危险因素，如遗传和行为因素，以产生全面的数据。
