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

Abstract

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)-1β, 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.

Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study

“…This might either be a reflection of facilitated penetration of peripheral virions into the CNS or that blood brain barrier impairment leads to an increased inflammatory response resulting in higher levels of locally replicated virus [ 28 ]. CSF HIV-RNA in the CNS OI group was also weakly associated with CSF pleocytosis, a finding previously observed in smaller studies [ 29 , 30 ] and in other CNS coinfections such as neuroborreliosis and herpes zoster [ 20 , 31 ]. By contrast, PML, an opportunistic CNS infection associated with only minor CNS inflammation, was not associated with an increased CSF viral burden.…”

Trends of tuberculosis meningitis and associated mortality in Texas, 2010-2017, a large population-based analysis

“…These risks, especially HIV infection, have been recognized as being associated with TBM [20–23]. A higher cerebrospinal fluid HIV-1 viral load has been observed in TBM patients in the setting of high TB and HIV infection prevalence [24]. However, immediate antiretroviral treatment initiation has been reported not to improve outcomes in TBM patients [25].…”

HIV-1C env and gag Variation in the Cerebrospinal Fluid and Plasma of Patients with HIV-Associated Cryptococcal Meningitis in Botswana

“…Variation in viral diversity in the CNS and peripheral blood has potentially important implications for HIV drug treatment and vaccine development and is considered to be a key barrier to successful HIV eradication [5]. Opportunistic infections of the CNS such as tuberculosis meningitis (TBM) have been shown to play a critical role in HIV compartmentalization [6]; however, there is limited evidence on whether or not cryptococcal meningitis (CM) have similar effects. Previous studies have shown that inflammation of the meninges caused by CM may result in the disruption of the blood-brain barrier (BBB), thereby causing the HIV-infected cells to easily penetrate the barrier into the CNS [7,8].…”