Tuberculosis Research Center, Indian Council of Medical Research, Chetput, Chennai, India.
Am J Respir Crit Care Med. 2010 Apr 1;181(7):743-51. doi: 10.1164/rccm.200903-0439OC. Epub 2009 Dec 3.
The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear.
To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ(3)/4HR(3) [ethambutol, 1,200 mg; isoniazid, 600 mg; rifampicin, 450 or 600 mg depending on body weight <60 or > or =60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ(3)/7HR(3)) in HIV/tuberculosis (TB).
HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment-naive during treatment.
Of the patients, 70% had culture-positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4(+) cell count was 160 cells/mm(3). Favorable response to antituberculosis treatment was similar by intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6M than in Reg9M (15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance.
Among antiretroviral treatment-naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment. Clinical Trials Registry Information: ID# NCT00376012 registered at www.clinicaltrials.gov.
完全间歇三联抗结核治疗方案（每周 3 次，共治疗 6 个月）治疗 HIV 相关结核病的疗效尚不清楚。
比较间歇 6 个月方案（Reg6M：2EHRZ（3）/4HR（3）[乙胺丁醇 1200mg；异烟肼 600mg；利福平 450 或 600mg，取决于体重<60 或≥60kg；吡嗪酰胺 1500mg，治疗 2 个月；随后用异烟肼和利福平治疗 4 个月，剂量与前 2 个月相同]）与 9 个月方案（Reg9M：2EHRZ（3）/7HR（3））治疗 HIV/TB 的疗效。
新诊断为肺或肺外结核的 HIV 感染者被随机分配到 Reg6M（n=167）或 Reg9M（n=160）组，并通过临床、免疫和细菌学参数监测 36 个月。主要结局包括治疗结束时的良好反应和随访期间的复发，次要结局为死亡。进行意向治疗和治疗期间分析。所有患者在治疗期间均未接受过抗逆转录病毒治疗。
患者中 70%有培养阳性的肺结核；中位病毒载量为 155000 拷贝/ml，CD4+细胞计数为 160 个细胞/mm3。意向治疗的治疗反应良好（Reg6M，83%和 Reg9M，76%；P=无显著差异）。尽管总体复发率无显著差异（Reg6M，19%和 Reg9M，13%），但 Reg6M 组的细菌学复发率明显高于 Reg9M 组（15%和 7%；P<0.05）。36 个月时，接受 Reg6M 的 36%患者和接受 Reg9M 的 35%患者死亡，两组之间无显著差异。所有 19 例治疗失败的患者均出现获得性利福平耐药（ARR），主要危险因素是基线异烟肼耐药。
在未接受过抗逆转录病毒治疗的 HIV 感染合并结核患者中，与 6 个月的每周 3 次间歇治疗方案相比，9 个月的治疗方案在治疗结束时的疗效相似，但细菌学复发率显著降低。这些间歇性方案的 ARR 率较高，延长结核病治疗并不能改变死亡率或 ARR。临床试验注册信息：ID#NCT00376012 在 www.clinicaltrials.gov 注册。
