Infectious Disease and International Health, Dartmouth Medical School, Hanover, New Hampshire, USA.
AIDS. 2010 Mar 13;24(5):675-85. doi: 10.1097/QAD.0b013e3283350f1b.
To determine whether a multiple-dose series of an inactivated whole cell mycobacterial vaccine, Mycobacterium vaccae, can prevent HIV-associated tuberculosis.
The DarDar trial was a randomized, placebo-controlled, double-blind trial. The study was carried in an outpatient facility in Dar es Salaam, Tanzania. HIV-infected patients with CD4 cell counts of at least 200 cells/microl and a Bacille Calmette-Guérin scar were chosen for the study. The intervention was carried out by random 1:1 assignment to five intradermal doses of M. vaccae or placebo. Tuberculin skin tests were performed, and patients with reactions of at least 5 mm were administered isoniazid for 6 months. The main outcome measures were disseminated (primary endpoint), definite, and probable tuberculosis (secondary endpoints).
Two thousand thirteen individuals were randomized (1006 to M. vaccae, 1007 to placebo) and followed every 3 months for a median of 3.3 years. The trial was terminated early because of slow accrual of cases of disseminated tuberculosis and significant protection against definite tuberculosis. Hazard ratios were disseminated tuberculosis 0.52 (95% confidence interval 0.21-1.34; seven cases in M. vaccae, 13 cases in placebo; log-rank P = 0.16), definite tuberculosis 0.61 (95% confidence interval 0.39-0.96; 33 cases in M. vaccae, 52 cases in placebo; P = 0.03), and probable tuberculosis 1.17 (95% confidence interval 0.76-1.80; 48 cases in M. vaccae, 40 cases in placebo; P = 0.46). Immunization was well tolerated, with no adverse effect on CD4 cell count or HIV viral load, and no increase in the rate of serious adverse events.
Administration of a multiple-dose series of M. vaccae to HIV-infected adults with childhood Bacille Calmette-Guérin immunization is safe and is associated with significant protection against definite tuberculosis. These results provide evidence that immunization with a whole cell mycobacterial vaccine is a viable strategy for the prevention of HIV-associated tuberculosis.
确定多次接种灭活全细胞分枝杆菌疫苗，即牛型分枝杆菌（Mycobacterium vaccae），能否预防与 HIV 相关的结核病。
DarDar 试验是一项随机、安慰剂对照、双盲试验。该研究在坦桑尼亚达累斯萨拉姆的一家门诊机构进行。选择 CD4 细胞计数至少为 200 个/μl 且有卡介苗疤痕的 HIV 感染者参与该研究。干预措施通过随机 1:1 分配接受 5 次皮内 M. vaccae 或安慰剂。进行结核菌素皮肤试验，对反应至少为 5 毫米的患者给予异烟肼治疗 6 个月。主要结局指标为播散性（主要终点）、明确和可能的结核病（次要终点）。
2013 人被随机分组（1006 人接受 M. vaccae，1007 人接受安慰剂），并在中位随访 3.3 年期间每 3 个月随访一次。由于播散性结核病病例的累积速度较慢以及对明确结核病的显著保护作用，试验提前终止。风险比为播散性结核病 0.52（95%置信区间 0.21-1.34；M. vaccae 组 7 例，安慰剂组 13 例；对数秩 P=0.16）、明确结核病 0.61（95%置信区间 0.39-0.96；M. vaccae 组 33 例，安慰剂组 52 例；P=0.03）和可能结核病 1.17（95%置信区间 0.76-1.80；M. vaccae 组 48 例，安慰剂组 40 例；P=0.46）。免疫接种耐受良好，对 CD4 细胞计数或 HIV 病毒载量无不良影响，严重不良事件发生率也无增加。
给有儿童卡介苗免疫史的 HIV 感染成人多次接种 M. vaccae 是安全的，与明确结核病的显著保护作用相关。这些结果提供了证据，表明用全细胞分枝杆菌疫苗进行免疫是预防与 HIV 相关结核病的可行策略。
