抗反转录病毒治疗期间发生的结核分枝杆菌感染导致撒哈拉以南非洲一个大型城市艾滋病毒临床机构的免疫重建效果不佳。
Incident tuberculosis during antiretroviral therapy contributes to suboptimal immune reconstitution in a large urban HIV clinic in sub-Saharan Africa.
机构信息
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
出版信息
PLoS One. 2010 May 7;5(5):e10527. doi: 10.1371/journal.pone.0010527.
BACKGROUND
Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.
METHODOLOGY/PRINCIPAL FINDINGS: Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm(3) (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100 pyar [95% CI 2.82-3.49]); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm(3) (hazard ratio [HR] 1.84 [1.25-2.70], P = 0.002) and male gender (HR 1.68 [1.34-2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm(3) [IQR; 107, 258, n = 118] vs 209 cells/mm(3) [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm(3): 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm(3): 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunological failure definitions.
CONCLUSIONS/SIGNIFICANCE: Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm(3). Incident TB during ART is associated with long-term impairment in immune recovery.
背景
抗逆转录病毒疗法（ART）可有效降低结核病（TB）的长期发病率，但与前 6 个月内的高 TB 发病率相关。我们旨在确定在乌干达一家大型城市 HIV 诊所中，ART 期间 TB 的发生率及其对 HIV 治疗结果的长期影响，以及 ART 期间发生 TB 的危险因素。
方法/主要发现：回顾性分析了所有首次接受一线 ART 治疗的患者的常规纵向临床数据。共纳入 5982 例患者，中位基线 CD4+T 细胞计数（CD4 计数）为 117 个细胞/mm³（四分位距 [IQR]；42，182）。在前 2 年中，在 10710 人年（py）的随访中发生了 336 例（5.6%）新发 TB 事件（3.14 例/100 pyar [95%CI 2.82-3.49]）；0-3、3-6、6-12 和 12-24 个月的发生率分别为 11.25（9.58-13.21）、6.27（4.99-7.87）、2.47（1.87-3.36）和 1.02（0.80-1.31）。ART 期间发生的新发 TB 与基线 CD4 计数<50 个细胞/mm³（风险比 [HR] 1.84 [1.25-2.70]，P=0.002）和男性性别（HR 1.68 [1.34-2.11]，P<0.001）独立相关。在 ART 治疗两年后，在前 12 个月内发生 TB 的患者的 CD4 计数增加中位数显著较低（184 个细胞/mm³[IQR；107，258，n=118]与 209 个细胞/mm³[124，309，n=2166]，P=0.01），根据两种定义，免疫重建不足的比例更大（CD4 计数增加<200 个细胞/mm³：57.4%与 46.9%，P=0.03，绝对 CD4 计数<200 个细胞/mm³：30.4%与 19.9%，P=0.006），并且根据世卫组织标准，免疫失败的百分比更高（13.6%与 6.5%，P=0.003）。ART 期间发生的新发 TB 与 CD4 计数恢复不良和符合世卫组织免疫失败定义独立相关。
结论/意义：ART 期间的新发 TB 最常发生在 3 个月内，且发生于 CD4 计数<50 个细胞/mm³的患者中。ART 期间发生的新发 TB 与长期免疫恢复受损相关。
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