背景:当标准治疗不可用时,HIV相关隐球菌性脑膜炎(CM)诱导治疗的最合适替代方案仍不清楚,无法访问,无法忍受,或无效。
方法:前瞻性,进行了多中心队列研究,以分析156例接受两性霉素B脱氧胆酸(AmB-D)+氟胞嘧啶(5FC)治疗的HIV感染CM患者的数据,伏立康唑(VCZ)+5FC,或AmB-D+氟康唑(Flu)作为诱导方案。临床疗效,累积死亡率,比较三个治疗组的不良反应。
结果:与接受AmB-D+流感的患者相比,接受AmB-D+5FC的患者在第4周和第10周发生的死亡较少[4(5.1%)与截至第4周,有8例(16.0%)死亡;危险比,1.8;95%置信区间[CI],1.0至3.3;p=0.039;8(10.3%)与截至第10周,死亡14人(28.0%);危险比,1.8;95%CI,1.1至2.7;p=0.008,分别]。发现AmB-D加5FC导致脑脊液(CSF)培养不育率明显更高(57.6%vs.到第2周,34%;87.9%与到第10周时为70%;两个比较的p<0.05)。然而,VCZ+5FC组和AmB-D+5FC组的CSF培养物不育性和死亡率差异无统计学意义.VCZ加5FC对新的艾滋病定义疾病的发病率和住院时间有显著的有利影响,与AmB-D加5FC相比。实验室不良事件(3级或4级),比如严重的贫血,VCZ+5FC的使用频率低于AmB-D联合5FC或流感的使用频率。
结论:我们的结果表明,与AmB-D加流感相比,AmB-D联合5FC仍然是更有效的诱导方案,当标准方案不容易获得时,VCZ+5FC可能是一种潜在的替代方案,可访问,耐受,或有效。
结果:注册编号,ChiCTR1900021195。2019年2月1日注册,http://www。chictr.org.cn/showproj.aspx?proj=35362。
BACKGROUND: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective.
METHODS: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups.
RESULTS: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use.
CONCLUSIONS: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective.
RESULTS: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .