Tuberculous meningitis is associated with higher cerebrospinal HIV-1 viral loads compared to other HIV-1-associated meningitides

被引:9
作者
Seipone, Ikanyeng D. [1 ]
Singh, Ravesh [1 ,2 ]
Patel, Vinod B. [3 ,4 ]
Singh, Avashna [1 ]
Gordon, Michelle L. [1 ]
Muema, Daniel M. [5 ,6 ]
Dheda, Keertan [7 ,8 ,9 ]
Ndung'u, Thumbi [1 ,5 ,10 ,11 ,12 ]
机构
[1] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
[2] Inkosi Albert Luthuli Cent Hosp, Dept Microbiol, Natl Hlth Lab Serv, KwaZulu Natal Acad Complex, Durban, South Africa
[3] Univ KwaZulu Natal, Inkosi Albert Luthuli Cent Hosp, Dept Neurol, Durban, South Africa
[4] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa
[5] Africa Hlth Res Inst, Durban, South Africa
[6] Kenya Govt Med Res Ctr, Wellcome Trust Res Program, Ctr Geog Med Res Coast, Kilifi, Kenya
[7] Univ Cape Town, Div Pulmonol, Lung Infect & Immun Unit, Cape Town, South Africa
[8] Univ Cape Town, Lung Inst, Dept Med, Cape Town, South Africa
[9] Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa
[10] MIT, Ragon Inst MGH, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[11] Harvard Univ, Cambridge, MA 02138 USA
[12] Max Planck Inst Infect Biol, Berlin, Germany
来源
PLOS ONE | 2018年 / 13卷 / 02期
基金
新加坡国家研究基金会; 英国惠康基金; 英国医学研究理事会;
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBRAL SPINAL-FLUID; T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; ANTIRETROVIRAL THERAPY; REPLICATION; DIAGNOSIS; PLEOCYTOSIS; CYTOKINES; FAILURE;
D O I
10.1371/journal.pone.0192060
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To gain a better understanding of the immunopathogenesis of tuberculous meningitis (TBM) and identify potential diagnostic biomarkers that may discriminate TBM from other HIV-1-associated meningitides, we assessed HIV-1 viral load levels, drug resistance patterns in antiretroviral therapy (ART)-experienced patients with persistent viremia and soluble immunological analytes in peripheral blood and cerebrospinal fluid (CSF) of HIV-1 infected patients with TBM versus other meningitides. One hundred and three matched blood and CSF samples collected from HIV-1 infected patients with TBM or other meningitides presenting at a hospital in Durban, South Africa, from January 2009 to December 2011 were studied. HIV-1 RNA and 28 soluble immunological potential biomarkers were quantified in blood plasma and CSF. Viremic samples were assessed for HIV-1 drug resistance mutations. There were 16 TBM, 46 probable TBM, 35 non-TBM patients, and six unclassifiable patients. TBM and non-TBM patients did not differ in median plasma viral load but TBM patients had significantly higher median CSF viral load than non-TBM participants (p = 0.0005). No major drug resistance mutations were detected in viremic samples. Interleukin (IL)-1 beta, IL-17, platelet derived growth factor (PDGF)-BB, granulocyte colony stimulating factor (G-CSF) and cathelicidin were significantly elevated in the CNS of TBM participants compared to other patients although these associations were lost after correction for false discovery. Our data suggest that TB co-infection of the CNS is associated with enhanced localized HIV-1 viral replication but none of the evaluated soluble immunological potential biomarkers could reliably distinguish TBM from other HIV-associated meningitides.
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页数:16
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