Background A 4-month regimen containing rifapentine and moxifloxacin has noninferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB). Methods In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing antiretroviral therapy (ART) (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200 mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB cotreatment (Weeks 4, 8, 12, and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if > 80% of participants had mid-interval efavirenz concentrations meeting this target. Results EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs without TB drugs was 0.79 (90% confidence interval [CI] .72–.85) in EFV1 and 0.84 [90% CI .69–.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations > 1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. Conclusions TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment. Clinical Trials Registration NCT 02410772.

中文翻译：

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接受每日大剂量利福喷丁结核病治疗的患者中依法韦仑的药代动力学和人类免疫缺陷病毒 1 型 (HIV-1) 病毒抑制


背景 与药物敏感结核病的标准 6 个月治疗方案相比，包含利福喷汀和莫西沙星的 4 个月治疗方案的疗效并不差。我们评估了每日大剂量利福喷汀治疗方案对人类免疫缺陷病毒 (HIV) 相关结核病 (TB) 患者依非韦伦药代动力学和病毒抑制的影响。方法 在一项 3 期随机对照试验中，已接受含依非韦伦抗逆转录病毒治疗 (ART) (EFV1) 病毒抑制的 HIV 阳性个体，或新开始依非韦伦 (EFV2) 接受含利福喷汀 (1200 mg) 的结核病治疗，异烟肼、吡嗪酰胺以及乙胺丁醇或莫西沙星。测量中间隔依非韦伦浓度 (a) ART 和 TB 联合治疗期间（第 4、8、12 和 17 周，EFV 组不同）和 (b) 单独服用 ART 时（TB 治疗前或后，周数） 0 和 22）。估计并比较表观口腔清除率（CL/F）。依非韦伦目标中间隔浓度为 > 1 mg/L。如果 > 80% 的参与者的中间间隔依非韦伦浓度达到该目标，则认为联合治疗是可接受的。结果 EFV1 和 EFV2 分别包括 70 名和 41 名可评估参与者。 EFV1 中使用依非韦伦 CL/F 与未使用结核药物的几何平均比为 0.79（90% 置信区间 [CI] .72–.85），EFV2 中为 0.84 [90% CI .69–.97]。第 0、4、8 和 17 周时 EFV1 中依非韦伦浓度为 > 1mg/L 的参与者百分比分别为 96%、96%、88% 和 89%。在 EFV2 中，在开始依非韦伦治疗后约 4 周和 8 周，该值为 98%。 结论 包含每日大剂量利福喷汀的结核病治疗适度降低（而不是增加）依非韦伦清除率，并且支持依非韦伦与这些方案一起使用而达到了治疗目标，无需调整剂量。临床试验注册 NCT 02410772。