Twice weekly tuberculosis preventive therapy in HIV infection in Zambia
Twice weekly tuberculosis preventive therapy in HIV infection in Zambia
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DOI：
10.1097/00002030-199818000-00014
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发表时间：
1998-12-24
期刊：
影响因子：
3.8
通讯作者：
Porter, JDH
中科院分区：
文献类型：
--
作者：
Mwinga, A;Hosp, M;Porter, JDH
背景：在赞比亚卢萨卡，开展了一项随机、双盲、安慰剂对照试验，以评估结核病(TB)预防治疗对感染HIV的成年人的疗效。主要观察指标为结核病发生率、死亡率和药物不良反应。方法：在2年的时间里，将1053名无临床结核病证据的HIV阳性患者随机分为异烟肼6个月/周2次(H组)、利福平3个月/周2次(R组)+吡津胺(Z组)或安慰剂3个月。治疗每周进行两次，并自行实施。结果：共对1053例受试者进行了1631人年的随访，中位数为1.8年。29名受试者因药物不良反应而停止治疗。在研究期间共诊断了96例结核病/疑似结核病(59例结核病和37例疑似结核病)，并报告了185例死亡。115名受试者(11%)在登记后任何时候都没有返回学习诊所。与安慰剂组相比，预防性治疗组(H组和RZ组)的结核病发病率以及结核病/疑似结核病的发病率均低于安慰剂组(发病率比=0.6，95%CI：0.36~1.01，P=0.057)。结核菌素皮试>5 mm者、淋巴细胞计数>2×10(9)/L>者、血红蛋白>10g/dl者预防性治疗效果较好。预防性治疗组和安慰剂组之间的死亡率没有差异。预防治疗的效果在研究的第一年后下降，到18个月时，治疗组的结核病发病率与安慰剂组相似。结论：本研究证明，预防治疗可以降低赞比亚HIV感染者的结核病发病率，无论是每周两次的异烟肼治疗6个月，还是利福平和吡嗪酰胺的联合治疗3个月。未观察到对死亡率的影响。在TST阳性或淋巴细胞计数在2×10(9)/L或更高的人中效果最好，这表明预防性治疗对免疫抑制程度较低的人可能更有效。这项研究报告的保护作用的有限持续时间提出了终生预防性治疗或再次预防的必要性的问题。(C)1998年，Lippincott Williams&Wilkins。
Background: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions.Methods: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB.Results: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2 x 10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group.Conclusion: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2 x 10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis. (C) 1998 Lippincott Williams & Wilkins.