Abstract：
BACKGROUND: Current guidelines recommend amphotericin B as the preferred drug for induction therapy; however, amphotericin B is not available in certain settings. Induction therapy with amphotericin B deoxycholate or voriconazole has been shown to be an effective treatment for talaromycosis. However, prospective clinical trials comparing these two antifungal drugs are absent from the literature.
METHODS: In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors.
RESULTS: We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291-0.696, p < 0.001; OR 0.443, 95% CI 0.261-0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333-0.793, p = 0.003; OR 0.542, 95% CI 0.318-0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4-36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1-34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup.
CONCLUSIONS: Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup.
BACKGROUND: ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .
METHODS: In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors.
RESULTS: We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291-0.696, p < 0.001; OR 0.443, 95% CI 0.261-0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333-0.793, p = 0.003; OR 0.542, 95% CI 0.318-0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4-36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1-34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup.
CONCLUSIONS: Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup.
BACKGROUND: ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .
摘要：
背景：目前的指南推荐两性霉素B作为诱导治疗的首选药物；然而，两性霉素B在某些设置中不可用。两性霉素B脱氧胆酸盐或伏立康唑的诱导治疗已被证明是一种有效的治疗方法。然而,文献中没有比较这两种抗真菌药物的前瞻性临床试验。
方法：在这个开放标签中，多中心，前瞻性对照试验,从2019年到2020年，我们在中国15家医院招募了患者。参与者在第一天以每公斤0.5至0.7mg/kg的剂量静脉注射两性霉素B脱氧胆酸盐或以6mg/kg的剂量静脉注射伏立康唑，每天两次。然后静脉注射4mg/kg，每天两次，持续3天，然后伏立康唑静脉给药(4mg/kg,每日两次)或口服给药(200mg,每日两次),持续剩余10天.主要结果是基线后48周内的全因死亡率。次要结果是第2周或第24周的死亡率，塔拉真菌病的临床消退，和第2周的真菌清除。进行倾向评分（PS）匹配分析以控制混杂因素。
结果：我们观察到，在第2周、第24周或第48周，在不匹配队列或匹配队列中，死亡风险均无差异。在无与伦比的和匹配的队列中，logistic回归分析显示,伏立康唑患者在第2周服用胆效霉素药物后,临床解决的比值比(OR0.450,95%CI0.291-0.696,p<0.001;OR0.443,95%CI0.261-0.752,p=0.003)和真菌清除率(OR0.514,95%CI0.318-0.923,p=0.024)显著降低。在无ART的诱导治疗亚组中，两性霉素B脱氧胆酸盐组患者的临床消退率和真菌清除率明显高于伏立康唑组（56.1％vs.30.4%,95%CI13.4-36.5，p=0.000；63.8%与40.4%,95%CI11.1-34.7，p=0.000），而诱导治疗联合ART亚组的临床消退率和真菌清除率无显著差异.
结论：使用伏立康唑的诱导治疗具有相似的疗效，就全因死亡率而言，在48周的观察期内，使用两性霉素B脱氧胆酸盐对HIV感染的塔拉真菌病患者进行诱导治疗。两性霉素B脱氧胆酸盐有助于在无ART亚组的诱导治疗中早期真菌清除和早期临床症状缓解。而在诱导治疗联合ART亚组中,使用两性霉素B脱氧胆酸盐对临床消退率和真菌清除率无显著影响.
背景：ChiCTR1900021195。2019年2月1日注册，http://www。chictr.org.cn/showproj.aspx?proj=35362。
方法：在这个开放标签中，多中心，前瞻性对照试验,从2019年到2020年，我们在中国15家医院招募了患者。参与者在第一天以每公斤0.5至0.7mg/kg的剂量静脉注射两性霉素B脱氧胆酸盐或以6mg/kg的剂量静脉注射伏立康唑，每天两次。然后静脉注射4mg/kg，每天两次，持续3天，然后伏立康唑静脉给药(4mg/kg,每日两次)或口服给药(200mg,每日两次),持续剩余10天.主要结果是基线后48周内的全因死亡率。次要结果是第2周或第24周的死亡率，塔拉真菌病的临床消退，和第2周的真菌清除。进行倾向评分（PS）匹配分析以控制混杂因素。
结果：我们观察到，在第2周、第24周或第48周，在不匹配队列或匹配队列中，死亡风险均无差异。在无与伦比的和匹配的队列中，logistic回归分析显示,伏立康唑患者在第2周服用胆效霉素药物后,临床解决的比值比(OR0.450,95%CI0.291-0.696,p<0.001;OR0.443,95%CI0.261-0.752,p=0.003)和真菌清除率(OR0.514,95%CI0.318-0.923,p=0.024)显著降低。在无ART的诱导治疗亚组中，两性霉素B脱氧胆酸盐组患者的临床消退率和真菌清除率明显高于伏立康唑组（56.1％vs.30.4%,95%CI13.4-36.5，p=0.000；63.8%与40.4%,95%CI11.1-34.7，p=0.000），而诱导治疗联合ART亚组的临床消退率和真菌清除率无显著差异.
结论：使用伏立康唑的诱导治疗具有相似的疗效，就全因死亡率而言，在48周的观察期内，使用两性霉素B脱氧胆酸盐对HIV感染的塔拉真菌病患者进行诱导治疗。两性霉素B脱氧胆酸盐有助于在无ART亚组的诱导治疗中早期真菌清除和早期临床症状缓解。而在诱导治疗联合ART亚组中,使用两性霉素B脱氧胆酸盐对临床消退率和真菌清除率无显著影响.
背景：ChiCTR1900021195。2019年2月1日注册，http://www。chictr.org.cn/showproj.aspx?proj=35362。
