CD4细胞计数<200个/μL的患者在结核病治疗一周后开始抗逆转录病毒治疗的疗效和安全性：TB-HAART研究，一项随机临床试验
Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial.
作者信息
Amogne Wondwossen, Aderaye Getachew, Habtewold Abiy, Yimer Getnet, Makonnen Eyasu, Worku Alemayhu, Sonnerborg Anders, Aklillu Eleni, Lindquist Lars
机构信息
Department of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Internal Medicine, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
Department of Internal Medicine, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
出版信息
PLoS One. 2015 May 12;10(5):e0122587. doi: 10.1371/journal.pone.0122587. eCollection 2015.
BACKGROUND
Given the high death rate the first two months of tuberculosis (TB) therapy in HIV patients, it is critical defining the optimal time to initiate combination antiretroviral therapy (cART).
METHODS
A randomized, open-label, clinical trial comparing efficacy and safety of efavirenz-based cART initiated one week, four weeks, and eight weeks after TB therapy in patients with baseline CD4 count < 200 cells/μL was conducted. The primary endpoint was all-cause mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring interruption of TB therapy, TB-associated immune reconstitution inflammatory syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear conversion rates. All analyses were intention-to-treat.
RESULTS
We studied 478 patients with median CD4 count of 73 cells/μL and 5.2 logs HIV RNA randomized to week one (n = 163), week four (n = 160), and week eight (n = 155). Sixty-four deaths (13.4%) occurred in 339.2 person-years. All-cause mortality rates at 48 weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test). All-cause mortality incidence rate ratios in subgroups with CD4 count below 50 cells/μL versus above were 2.8 in week one (95% CI 1.2-6.7), 3.1 in week four (95% CI 1.2-8.6) and 5.1 in week eight (95% CI 1.8-16). Serum albumin < 3 gms/dL (adjusted HR, aHR = 2.3) and CD4 < 50 cells/μL (aHR = 2.7) were independent predictors of mortality. Compared with similar subgroups from weeks four and eight, first-line TB treatment interruption was high in week one deaths (P = 0.03) and in the CD4 subgroup <50 cells/μL (P = 0.02).
CONCLUSIONS
Antiretroviral therapy one week after TB therapy doesn't improve overall survival. Despite increased mortality with CD4 < 50 cells/μL, we recommend cART later than the first week of TB therapy to avoid serious hepatotoxicity and treatment interruption.
TRIAL REGISTRATION
ClinicalTrials.gov NCT 01315301.
背景
鉴于HIV患者在结核病（TB）治疗的头两个月死亡率较高，确定开始联合抗逆转录病毒治疗（cART）的最佳时间至关重要。
方法
开展了一项随机、开放标签的临床试验，比较基线CD4细胞计数<200个/μL的患者在结核病治疗后1周、4周和8周开始基于依非韦伦的cART的疗效和安全性。主要终点是48周时的全因死亡率。次要终点包括需要中断结核病治疗的肝毒性、结核病相关免疫重建炎症综合征、新的艾滋病定义疾病、CD4细胞计数、HIV RNA水平和抗酸杆菌涂片转阴率。所有分析均采用意向性治疗。
结果
我们研究了478例患者，其CD4细胞计数中位数为73个/μL，HIV RNA为5.2 log，随机分为1周组（n = 163）、4周组（n = 160）和8周组（n = 155）。在339.2人年中发生了64例死亡（13.4%）。48周时的全因死亡率在1周组为每100人年25例，4周组为每100人年18例，8周组为每100人年15例（对数秩检验P = 0.2）。CD4细胞计数低于50个/μL的亚组与高于50个/μL的亚组相比，全因死亡率发生率比在1周组为2.8（95%CI 1.2 - 6.7），4周组为3.1（95%CI 1.2 - 8.6），8周组为5.1（95%CI 1.8 - 16）。血清白蛋白<3 gms/dL（调整后HR，aHR = 2.3）和CD4<50个/μL（aHR = 2.7）是死亡率的独立预测因素。与4周和8周的相似亚组相比，1周死亡组中一线结核病治疗中断率较高（P = 0.03），CD4亚组<50个/μL时也较高（P = 0.02）。
结论
结核病治疗1周后开始抗逆转录病毒治疗并不能改善总体生存。尽管CD4<50个/μL时死亡率增加，但我们建议在结核病治疗1周后更晚开始cART，以避免严重肝毒性和治疗中断。
试验注册
ClinicalTrials.gov NCT 01315301。
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