Myint Thein, Anderson Albert M, Sanchez Alejandro, Farabi Alireza, Hage Chadi, Baddley John W, Jhaveri Malhar, Greenberg Richard N, Bamberger David M, Rodgers Mark, Crawford Timothy N, Wheat L Joseph
From Division of Infectious Diseases (TM, RNG), Department of Internal Medicine, and Department of Public Health (TNC), University of Kentucky, Lexington, Kentucky; Division of Infectious Diseases (AMA), Department of Internal Medicine, Emory University, Atlanta, Georgia; Division of Infectious Diseases (AS), Department of Internal Medicine, University of Southern California, Los Angeles, California; Division of Infectious Diseases (AF), Department of Internal Medicine, University Medical Center of Southern Nevada, Las Vegas, Nevada; Department of Pulmonary and Critical Care Medicine, Thoracic Transplantation (CH), Indiana University Health, Indianapolis, Indiana; Division of Infectious Disease (JWB), Department of Internal Medicine, University of Alabama, Birmingham, Alabama; Departmentof Epidemiology (MJ), College of Public Health, University of Louisville, Louisville, Kentucky; Division of Infectious Disease (DMB), Department of Internal Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri; and MiraVista Diagnostics (MR, LJW), Indianapolis, Indiana.
Medicine (Baltimore). 2014 Jan;93(1):11-18. doi: 10.1097/MD.0000000000000016.
Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91-55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL. Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.
尽管对于获得性免疫缺陷综合征（AIDS）相关组织胞浆菌病患者，在免疫功能恢复后停用抑制性抗真菌治疗已被认可，但临床实践中尚未有关于这种方法的发表研究，且对复发患者的特征描述极少。我们进行了一项多中心回顾性队列研究，以确定AIDS患者停用组织胞浆菌病抑制性抗真菌治疗后的结局。97例患者被分为医生停用抑制性治疗组（PD）（38例患者）和医生继续抑制性治疗组（PC）（59例患者）。两组在基线时无统计学差异，但在治疗中断时和最近一次随访时，在治疗依从性、人类免疫缺陷病毒（HIV）RNA和尿组织胞浆菌抗原浓度方面存在显著差异。PD组未出现因组织胞浆菌病导致的复发或死亡，而PC组的复发率为36%（p < 0.0001），死亡率为5%（p = 0.28）。53%的不依从患者出现了复发，而依从患者未出现复发（p < 0.0001）。初始患有中枢神经系统（CNS）组织胞浆菌病的患者中有67%复发，而无CNS受累的患者中这一比例为15%（p = 0.0004），这可能是由于不依从所致。此外，在1年随访时尿抗原水平高于2.0 ng/mL的患者复发可能性是尿抗原水平低于2.0 ng/mL患者的12.82倍（95%置信区间，2.91 - 55.56）。对于完成至少1年抗真菌治疗、CD4细胞计数>150个/mL、HIV RNA <400拷贝/mL、组织胞浆菌尿抗原<2 ng/mL（相当于第二代方法中<4.0单位）且无CNS组织胞浆菌病的依从患者，停用抗真菌治疗是安全的。
