无症状隐球菌抗原血症的HIV感染者的神经认知功能：三个前瞻性队列的比较
Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: a comparison of three prospective cohorts.
作者信息
Montgomery Martha P, Nakasujja Noeline, Morawski Bozena M, Rajasingham Radha, Rhein Joshua, Nalintya Elizabeth, Williams Darlisha A, Huppler Hullsiek Kathy, Kiragga Agnes, Rolfes Melissa A, Donahue Carlson Renee, Bahr Nathan C, Birkenkamp Kate E, Manabe Yukari C, Bohjanen Paul R, Kaplan Jonathan E, Kambugu Andrew, Meya David B, Boulware David R
机构信息
Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, 3-222 MTRF, 2001 6th St SE, Minneapolis, MN, 55455, USA.
Infectious Disease Institute, Makerere University, Kampala, Uganda.
出版信息
BMC Neurol. 2017 Jun 12;17(1):110. doi: 10.1186/s12883-017-0878-2.
BACKGROUND
HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia.
METHODS
Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants.
RESULTS
Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001).
CONCLUSION
Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.
背景
与血液中隐球菌抗原（CrAg）检测不到的HIV感染者相比，血液中可检测到CrAg的HIV感染者发病率和死亡率更高。本研究调查了无症状隐球菌抗原血症患者的神经认知功能。
方法
来自三个前瞻性HIV队列的参与者在开始抗逆转录病毒治疗（ART）时接受了神经认知测试。队列包括患有隐球菌性脑膜炎的患者（N = 90）、无症状CrAg阳性患者（N = 87）以及无中枢神经系统感染的HIV感染者（N = 125）。相对于乌干达HIV阴性人群，计算每项神经认知测试的Z分数，并根据八个测试领域创建综合定量神经认知表现Z分数（QNPZ - 8）。对所有三个队列在ART治疗前进行神经认知功能测量，对于无症状CrAg阳性参与者，在ART治疗4周后（以及先发制性氟康唑治疗6周后）额外进行测量。
结果
隐球菌性脑膜炎患者和无症状CrAg阳性参与者的CD4细胞计数中位数（分别为17和26个细胞/μL）低于HIV感染对照队列（233个细胞/μL），且卡诺夫斯基功能状态也较低（分别为60和70，而对照队列是90）。无症状CrAg阳性参与者的综合QNPZ - 8（Z分数为 - 1.80）介于隐球菌性脑膜炎队列（Z分数为 - 2.22，P = 0.02）和HIV感染对照队列（Z分数为 - 1.36，P = 0.003）之间。在ART治疗4周和氟康唑治疗6周后，无症状CrAg阳性队列的神经认知表现有所改善（Z分数为 - 1.0，P < 0.001）。
结论
在晚期HIV/AIDS的无症状CrAg阳性患者中，即使没有脑膜炎的体征或后遗症，也发现了明显的神经认知功能缺陷。在开始先发制性氟康唑治疗和ART后，该组的神经认知功能会随着时间改善，但可能需要短期的依从性支持。
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