背景:组织胞浆菌病是拉丁美洲一种主要的艾滋病定义疾病。脂质体两性霉素B(L-AmB)是治疗的首选药物,但由于常规长期治疗方案的药物和住院费用较高,因此准入受到限制。
方法:用L-AmB与对照进行1-或2-剂量诱导治疗艾滋病播散性组织胞浆菌病的前瞻性随机多中心开放标签试验,随后口服伊曲康唑治疗。我们将受试者随机分为:(i)单剂量10mg/kg的L-AmB;(ii)D1上10mg/kg的L-AmB,D3上5mg/kg的L-AmB;(iii)每天3mg/kg的L-AmB,持续2周(对照)。主要结果是第14天的临床反应(发烧和归因于组织胞浆菌病的体征/症状的消退)。
结果:共有118名受试者被随机分组,和中位CD4+计数,两组之间的临床表现相似。输液相关毒性,在多个时间点的肾脏毒性,和贫血的频率,低钾血症,低镁血症,和肝脏毒性相似。单剂量L-AmB的第14天临床反应为84%,69%2剂量L-AmB,控制臂为74%(P=0.69)。单剂量L-AmB在D14的总生存率为89.0%(34/38),2剂量L-AmB的78.0%(29/37),控制臂为92.1%(35/38)(P=0.82)。
结论:在AIDS相关的组织胞浆菌病中,使用10mg/kg的L-AmB进行一天的诱导治疗是安全的。尽管临床反应可能不劣于标准L-AmB治疗,需要进行验证性III期临床试验.单一诱导剂量将显著降低药物获取成本(>4倍),并显著缩短和简化治疗,这是增加访问的关键点。
Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.
Prospective randomized multicenter open-label
trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14.
A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82).
One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical
trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.