Moyo Melanie, Lawrence David S, Jafali James, Molloy Síle F, Kumwenda Johnstone, Kanyama Cecilia, Hosseinipour Mina C, Ndhlovu Chiratidzo E, Mosepele Mosepele, Meya David B, Rhein Joshua, Boulware David R, Muzoora Conrad, Gupta Rishi K, Samuels Thomas H A, Youssouf Nabila, Chammard Timothée Boyer, Lortholary Olivier, Schutz Charlotte, Meintjes Graeme, Mwandumba Henry C, Harrison Thomas S, Jarvis Joseph N
Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Department of Medicine, Kamuzu University of Health Sciences, Blantyre, Malawi.
Clin Infect Dis. 2025 Aug 1;81(1):75-83. doi: 10.1093/cid/ciae586.
More than half of people diagnosed with human immunodeficiency virus-associated cryptococcal meningitis are antiretroviral therapy (ART)-experienced. The impact of recent ART initiation (≤14 days) on outcomes from cryptococcal meningitis, and how to optimally manage ART in this patient population, are unknown.
We analyzed data from the recent Ambisome Therapy Induction Optimisation (AMBITION) trial to (1) examine whether patients diagnosed with cryptococcal meningitis within 14 days of ART initiation are at higher risk of mortality and (2) determine the impact of ART interruption at diagnosis of cryptococcal meningitis. Combined data from the AMBITION trial and the earlier Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa trial were analyzed to describe baseline characteristics of patients according to ART status.
Among the 810 AMBITION participants, adjusted 2-week mortality risk was 20.8% (95% confidence interval [CI]: 11.5-30.2; 26/120) in those on ART for 14 days or less at presentation, 10.4% (95% CI: 3.6-17.2; 18/130) on ART for >2 weeks to 2 months, 7.1% (95% CI: 0-14.9; 7/92) on ART for >2 months to 6 months, and 13.0% (95% CI: 8.5-17.6; 50/307) in those on ART for more than 6 months compared to 12.4% (95% CI: 9.2-15.5; 111/707) among individuals not on ART. In the combined dataset, baseline fungal burdens were lower and baseline CD4 counts were higher with increasing ART duration. Among individuals on ART for ≤14 days at presentation, 2-week mortality was 35% (8/23) in those continuing ART versus 14% (7/49) in those discontinuing ART.
Mortality from cryptococcal meningitis was higher in recent ART initiators. ART interruption in this group may lead to improved outcomes.
超过半数被诊断为人类免疫缺陷病毒相关隐球菌性脑膜炎的患者都接受过抗逆转录病毒治疗（ART）。近期开始ART治疗（≤14天）对隐球菌性脑膜炎预后的影响，以及如何在该患者群体中优化ART治疗，目前尚不清楚。
我们分析了近期的两性霉素B脂质体治疗诱导优化（AMBITION）试验的数据，以（1）检查在开始ART治疗14天内被诊断为隐球菌性脑膜炎的患者是否有更高的死亡风险，以及（2）确定在诊断隐球菌性脑膜炎时中断ART治疗的影响。分析了AMBITION试验和早期非洲隐球菌性脑膜炎抗真菌联合治疗试验的合并数据，以根据ART治疗状态描述患者的基线特征。
在810名AMBITION试验参与者中，就诊时接受ART治疗14天或更短时间的患者，调整后的2周死亡风险为20.8%（95%置信区间[CI]：11.5 - 30.2；26/120），接受ART治疗超过2周但少于2个月的患者为10.4%（95%CI：3.6 - 17.2；18/130），接受ART治疗超过2个月但少于6个月的患者为7.1%（95%CI：0 - 14.9；7/92），接受ART治疗超过6个月的患者为13.0%（95%CI：8.5 - 17.6；50/307），而未接受ART治疗的个体为12.4%（95%CI：9.2 - 15.5；111/707）。在合并数据集中，随着ART治疗持续时间的增加，基线真菌负荷较低，基线CD4细胞计数较高。就诊时接受ART治疗≤14天的个体中，如果继续接受ART治疗，2周死亡率为35%（8/23），而中断ART治疗的个体为14%（7/49）。
近期开始ART治疗的患者中，隐球菌性脑膜炎的死亡率较高。在该组中中断ART治疗可能会改善预后。
