Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia.
Research & Development Department, Drugs for Neglected Diseases initiative, Geneva, Switzerland.
PLoS Negl Trop Dis. 2019 Jan 17;13(1):e0006988. doi: 10.1371/journal.pntd.0006988. eCollection 2019 Jan.
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS: An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment. Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45-87%) in the unadjusted analysis, and 50% (95% CI 27-73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67-90%) and 67% (95% CI 48-82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32-78%) in the monotherapy arm, and 88% (95% CI 79-98%) in the combination arm. No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE: The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
www.clinicaltrials.gov NCT02011958.
内脏利什曼病（VL）合并人类免疫缺陷病毒（HIV）感染患者需要特殊的病例管理。世界卫生组织推荐使用 40mg/kg 的两性霉素 B 脂质体单药治疗。本研究的目的是评估较低剂量两性霉素 B 脂质体联合米替福新在治疗结束时是否具有可接受的疗效。
方法/主要发现：在埃塞俄比亚合并 HIV 的 VL 患者中进行了一项开放性、非对照、随机试验，比较了两性霉素 B 脂质体（30mg/kg）联合米替福新（28 天，每天 100mg）与两性霉素 B 脂质体单药（40mg/kg）治疗的疗效（NCT02011958）。采用序贯设计，具有三角形延续区。主要终点为第一轮治疗后第 29 天的寄生虫清除率。第 29 天临床改善但寄生虫未清除的患者接受第二轮分配的治疗。治疗完成后第 58 天再次评估疗效。根据预先指定的停止规则，分别在单药组和联合组纳入 19 例和 39 例患者后停止入组。在未经调整的分析中，第 29 天两性霉素 B 组的意向治疗疗效为 70%（95%CI 45-87%），调整后的疗效为 50%（95%CI 27-73%），而联合组的疗效分别为 81%（95%CI 67-90%）和 67%（95%CI 48-82%）。第 58 天，单药组调整后的疗效为 55%（95%CI 32-78%），联合组为 88%（95%CI 79-98%）。未发现与研究药物相关的重大安全性问题。治疗期间共观察到 10 例严重不良事件（SAE），4 例死亡与研究药物无关。
延长治疗时间的联合治疗方案在 HIV-VL 患者中显示出了最高的疗效记录；这些结果支持将该方案作为东非 HIV-VL 患者的一线治疗策略。
www.clinicaltrials.gov NCT02011958。
