Burza Sakib, Mahajan Raman, Sinha Prabhat K, van Griensven Johan, Pandey Krishna, Lima María Angeles, Sanz Marta Gonzalez, Sunyoto Temmy, Kumar Sunil, Mitra Gaurab, Kumar Ranjeet, Verma Neena, Das Pradeep
Médecins Sans Frontières, New Delhi, India; Institute of Tropical Medicine, Antwerp, Belgium.
Médecins Sans Frontières, New Delhi, India.
PLoS Negl Trop Dis. 2014 Aug 7;8(8):e3053. doi: 10.1371/journal.pntd.0003053. eCollection 2014 Aug.
Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.
Intravenous AmBisome (20-25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4-10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4-51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7-14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64-66% reduced risk of mortality and 75% reduced risk of relapse.
This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management.
内脏利什曼病（VL；又称黑热病）是印度比哈尔邦一种最终会致命的地方性疾病，而艾滋病毒/艾滋病在该地区是一种新兴疾病。2011年在比哈尔邦进行的一项观察性队列研究涉及55例接受20 - 25mg/kg静脉注射脂质体两性霉素B（安必素）治疗的VL/HIV合并感染患者，估计其2年内生存概率为85.5%，VL复发概率为26.5%。在此，我们报告2007年至2012年期间接受该方案治疗的更大规模合并感染患者队列的长期实地研究结果。
159例VL/HIV合并感染患者（包括初发感染和复发患者）接受静脉注射安必素（20 - 25mg/kg），分4 - 10天给予4或5剂，每剂5mg/kg。出院时VL的初始治愈定义为症状改善、发热停止、食欲改善和脾肿大消退。未常规进行治愈检测。分别有23例（14.5%）、39例（24.5%）和61例（38.4%）患者在入院前、入院期间和入院后开始接受抗逆转录病毒治疗（ART）。所有出院患者均实现了初始治愈。随访期间共有36例患者死亡，其中6例在入院后不久死亡。死亡发生在开始VL治疗后的中位时间为11周（四分位间距4 - 51周）。治疗后6个月、2年和4年的估计死亡风险分别为14.3%、22.4%和29.7%。在153例出院患者中，随访期间诊断出26例VL复发，复发发生在出院后的中位时间为10个月（四分位间距7 - 14个月）。在考虑竞争风险后，1年、2年和4年的估计复发风险分别为16.1%、20.4%和25.9%。低血红蛋白水平和合并结核感染是死亡的独立危险因素，而在VL治疗入院后不久开始ART与死亡风险降低64 - 66%和复发风险降低75%相关。
这是印度次大陆报道的最大规模的HIV - VL合并感染患者队列。即使在用安必素治疗后实现了初始治愈，这些患者的VL复发率和死亡率似乎比未感染艾滋病毒的患者高得多，尽管复发率在2年后似乎趋于稳定。这些结果扩展了早期的研究发现，即合并感染患者死亡风险增加，需要多学科方法进行长期管理。
