Tryptophan metabolism and its relationship with central nervous system toxicity in people living with HIV switching from efavirenz to dolutegravir.

Abstract:

:The mechanisms underlying central nervous system (CNS) toxicities in antiretroviral-treated persons living with HIV (PLWH) remain elusive. We investigated the associations between markers of tryptophan metabolism and measurements of CNS toxicity in PLWH. In a prospective study, virologically suppressed PLWH receiving efavirenz-containing antiretroviral regimens with ongoing CNS toxicity were switched to dolutegravir-containing regimens and followed up for 12 weeks. Plasma tryptophan and kynurenine concentrations and the kynurenine/tryptophan ratio were calculated. Ten CNS toxicities were graded according to the ACTG adverse events scale. Scores ranged from 0 (none) to 3 (severe) and were summed, giving a total from 0 to 30. Paired-samples t tests and linear mixed model analyses were conducted to assess changes in, and relationships between, laboratory and clinical parameters. Mean kynurenine plasma concentration increased from baseline to week 12 (2.15 to 2.50 μmol/L, p = 0.041). No significant changes were observed for tryptophan (54.74 to 56.42 μmol/L, p = 1.000) or kynurenine/tryptophan ratio (40.37 to 41.08 μmol/L, p = 0.276). Mean CNS toxicity score decreased from 10.00 to 4.63 (p < 0.001). Plasma kynurenine concentration correlated with CNS toxicity score: for every 1 μmol/L increase in kynurenine concentration observed, a 1.7 point decrease was observed in CNS toxicity score (p < 0.038). A similar trend was observed for the kynurenine/tryptophan ratio: for every 1 μmol/mmol increase observed in kynurenine/tryptophan ratio, a 0.1 point decrease was observed in CNS toxicity score (p = 0.054). Switching from efavirenz to dolutegravir was associated with increases in plasma kynurenine concentration and improvements in CNS toxicity scores. Underlying mechanisms explaining the rise in kynurenine concentrations need to be established.

journal_name

J Neurovirol

journal_title

Journal of neurovirology

authors

Keegan MR,Winston A,Higgs C,Fuchs D,Boasso A,Nelson M

doi

10.1007/s13365-018-0688-3

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

85-90

issue

1

eissn

1355-0284

issn

1538-2443

pii

10.1007/s13365-018-0688-3

journal_volume

25

pub_type

杂志文章,多中心研究
  • Restricted replication of herpes simplex virus in satellite glial cell cultures clonally derived from adult mice.

    abstract::To determine the possible influence of satellite glial cells on restricting the spread of herpes simplex virus in the peripheral nervous system, HSV replication was studied in clonally derived cultures of satellite glial cells from adult animals. Satellite cells were purified by exploiting their close anatomical assoc...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.3109/13550289909029479

    authors: Wilkinson R,Leaver C,Simmons A,Pereira RA

    更新日期:1999-08-01 00:00:00

  • Incidence of symptomatic CSF viral escape in HIV infected patients receiving atazanavir/ritonavir (ATV/r)-containing ART: a tertiary care cohort in western India.

    abstract::This single-center study attempts to quantify the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving atazanavir/r (ATV/r)-containing regimen. We performed a retrospective analysis of patients receiving ATV/r-containing ART who were diagnosed with symptomatic CSFVE from August 2012 to January 2017....

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-018-0642-4

    authors: Patel AK,Patel KK,Gohel S,Kumar A,Letendre S

    更新日期:2018-08-01 00:00:00

  • Plasma CXCL10 correlates with HAND in HIV-infected women.

    abstract::HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhoo...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-019-00785-4

    authors: Burlacu R,Umlauf A,Marcotte TD,Soontornniyomkij B,Diaconu CC,Bulacu-Talnariu A,Temereanca A,Ruta SM,Letendre S,Ene L,Achim CL

    更新日期:2020-02-01 00:00:00

  • Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection.

    abstract::Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-i...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-014-0250-x

    authors: Meyer VJ,Little DM,Fitzgerald DA,Sundermann EE,Rubin LH,Martin EM,Weber KM,Cohen MH,Maki PM

    更新日期:2014-08-01 00:00:00

  • Decreased MEG beta oscillations in HIV-infected older adults during the resting state.

    abstract::The introduction of combination antiretroviral therapy significantly reduced the prevalence of the most severe form of HIV-associated neurocognitive disorders (HAND). Despite this decline, 35-70 % of HIV-infected patients continue to develop mild motor and cognitive impairments. Although neuropsychological studies hav...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-013-0220-8

    authors: Becker KM,Heinrichs-Graham E,Fox HS,Robertson KR,Sandkovsky U,O'Neill J,Swindells S,Wilson TW

    更新日期:2013-12-01 00:00:00

  • HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor neurons, of the rat peripheral nervous system.

    abstract::The entry of herpes simplex virus (HSV)-1 into cells is a complex process mediated in part by the binding of the HSV glycoprotein D (gD) to a specific cellular receptor identified as HveC, or nectin-1. We examined the distribution of HveC in sensory and motor neurons of the peripheral nervous system (PNS) by immunocyt...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/135502801753170336

    authors: Mata M,Zhang M,Hu X,Fink DJ

    更新日期:2001-10-01 00:00:00

  • Host and virus strain dependence in activation of human macrophages by human immunodeficiency virus type 1.

    abstract::Human immunodeficiency virus type 1 (HIV-1)-associated neuropathogenesis occurs in a large minority of infected people. Presently, there are neither viral nor cellular markers that predict the development of brain disease during HIV-1 infection. This study was conducted to determine whether there exist systematic diff...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280701510104

    authors: Kazmierczak K,Potash MJ

    更新日期:2007-10-01 00:00:00

  • Acute exposure to ethanol potentiates human immunodeficiency virus type 1 Tat-induced Ca(2+) overload and neuronal death in cultured rat cortical neurons.

    abstract::A significant number of human immunodeficiency virus type 1 (HIV-1)-infected patients are alcoholics. Either alcohol or HIV alone induces morphological and functional damage to the nervous system. HIV-1 Tat is a potent transcriptional activator of the viral promoter, with the ability to modulate a number of cellular r...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280500516427

    authors: Brailoiu E,Brailoiu GC,Mameli G,Dolei A,Sawaya BE,Dun NJ

    更新日期:2006-02-01 00:00:00

  • Progressive multifocal leukoencephalopathy despite immune recovery in a HIV/HCV co-infected patient.

    abstract::In HIV patients, HCV co-infection has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Furthermore, PML has also been described in patients with cirrhosis, whether related to HCV infection or not. We describe here the case of a HIV/HCV co-infected patient with cirrhosis who d...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-020-00848-x

    authors: Hentzien M,Guihot A,de Maindreville D,Tabary T,Brodard V,Vieillard V,Adle-Biassette H,Bani-Sadr F

    更新日期:2020-08-01 00:00:00

  • Diplopia as isolated presentation of varicella zoster central nervous system reactivation.

    abstract::Here, we report a patient who developed diplopia secondary to a right cranial nerve III and IV palsy, as well as fever and headache. Cerebrospinal fluid analysis (CSF) showed high varicella-zoster virus (VZV)-DNA viral load (>300,000,000 copies/ml). VZV antibodies in CSF was ≥1:16. Diagnosis of neurological reactivati...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-017-0534-z

    authors: Del Borgo C,Belvisi V,Valli MB,Currà A,Pozzetto I,Sepe M,Mastroianni CM

    更新日期:2017-08-01 00:00:00

  • Association of HIV serostatus and metabolic syndrome with neurobehavioral disturbances.

    abstract::Metabolic syndrome (MetS), a constellation of related metabolic risk factors, is a common comorbidity associated with cognitive difficulty in people living with HIV (PLWH). Neurobehavioral disturbances (e.g., behavioral manifestations of frontal-subcortical dysfunction) are also prevalent in HIV, yet the role MetS mig...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-020-00878-5

    authors: Pope CN,Montoya JL,Vasquez E,Pérez-Santiago J,Ellis R,McCutchan JA,Jeste DV,Moore DJ,Marquine MJ

    更新日期:2020-12-01 00:00:00

  • Pain, psychoaffective symptoms, and quality of life in human T cell lymphotropic virus type 1 (HTLV-1): a cross-sectional study.

    abstract::The objective of this study is to describe the chronic pain characteristics in individuals infected with human T cell lymphotropic virus type 1 (HTLV-1) per subgroup (asymptomatic, oligosymptomatic, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)) compared with controls with chronic pain withou...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-020-00914-4

    authors: Dos Santos DN,Sá KN,Queirós FC,Paixão AB,Santos KOB,de Andrade RCP,Camatti JR,Baptista AF

    更新日期:2021-01-06 00:00:00

  • COVID-19 and the nervous system.

    abstract::A pandemic due to novel coronavirus arose in mid-December 2019 in Wuhan, China, and in 3 months' time swept the world. The disease has been referred to as COVID-19, and the causative agent has been labelled SARS-CoV-2 due to its genetic similarities to the virus (SARS-CoV-1) responsible for the severe acute respirator...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章,评审

    doi:10.1007/s13365-020-00840-5

    authors: Berger JR

    更新日期:2020-04-01 00:00:00

  • PCR detection of host and HIV-1 sequences from archival brain tissue.

    abstract::Mutations in CCR5 and CCR2b have been recently shown to affect disease progression towards AIDS. A role for these host genotypes in AIDS dementia complex (ADC) has also been postulated but remains unclear. Additionally, brain-derived envelope sequences from HIV-1 have been associated with ADC but their specific contri...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.3109/13550280009013160

    authors: Smith KM,Crandall KA,Kneissl ML,Navia BA

    更新日期:2000-04-01 00:00:00

  • Impact of direct virus-induced neuronal dysfunction and immunological damage on the progression of flavivirus (Modoc) encephalitis in a murine model.

    abstract::Flavivirus encephalitis is believed to be the result of two main mechanisms: (i) direct damage to and dysfunction of neurons as a result of viral replication and (ii) destruction of the brain tissue by an inflammatory response. The differential impact of both mechanisms on the progression of flavivirus encephalitis ha...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280390173319

    authors: Leyssen P,Paeshuyse J,Charlier N,Van Lommel A,Drosten C,De Clercq E,Neyts J

    更新日期:2003-02-01 00:00:00

  • The "Three Italy" of the COVID-19 epidemic and the possible involvement of SARS-CoV-2 in triggering complications other than pneumonia.

    abstract::Coronavirus disease 2019 (COVID-19), first reported in Wuhan, the capital of Hubei, China, has been associated to a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization declared the SARS-CoV-2 infection a global pandemic. Soon after, the numb...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章,评审

    doi:10.1007/s13365-020-00862-z

    authors: Prezioso C,Marcocci ME,Palamara AT,De Chiara G,Pietropaolo V

    更新日期:2020-06-01 00:00:00

  • NKG2D contributes to efficient clearance of picornavirus from the acutely infected murine brain.

    abstract::Activated murine cytotoxic T cells express the NKG2D natural cytotoxicity receptor. This receptor recognizes major histocompatibility complex (MHC) class I-like molecules expressed on the surface of infected cells and serves to augment T cell-mediated cytotoxicity. The role of NKG2D-mediated augmentation in the cleara...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280802105002

    authors: Deb C,Howe CL

    更新日期:2008-05-01 00:00:00

  • Expression of TSLC1 in patients with HAM/TSP.

    abstract::Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic myelopathy characterized by slowly progressive spastic paraparesis and urinary dysfunction. A few biomarkers in the cerebrospinal fluid are known to be related to disease activity, but no biomarker has be...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-020-00838-z

    authors: Takenouchi N,Tanaka M,Sato T,Yao J,Fujisawa JI,Izumo S,Kubota R,Matsuura E

    更新日期:2020-06-01 00:00:00

  • Efficient infection of brain microvascular endothelial cells by an in vivo-selected neuroinvasive SIVmac variant.

    abstract::A neuroinvasive/neuropathogenic SIV variant termed SIVmac182 was previously isolated and characterized (Watry et al, 1994). This neuroinvasive strain was derived from the uncloned strain SIVmac251 through serial animal passage of infected microglia, unlike previously reported neurovirulent strains. Importantly, the vi...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.3109/13550289809114528

    authors: Strelow LI,Watry DD,Fox HS,Nelson JA

    更新日期:1998-06-01 00:00:00

  • Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals.

    abstract::Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neu...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-016-0497-5

    authors: Pérez-Santiago J,De Oliveira MF,Var SR,Day TRC,Woods SP,Gianella S,Mehta SR

    更新日期:2017-04-01 00:00:00

  • Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals.

    abstract::With aging of HIV populations, there is concern that Alzheimer's disease (AD) may become prevalent and difficult to distinguish from HIV-associated neurocognitive disorders. To date, there are no reports documenting histologically verified Alzheimer's neuropathology in individuals with HIV and dementia. Herein, we rep...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-018-0663-z

    authors: Morgello S,Jacobs M,Murray J,Byrd D,Neibart E,Mintz L,Meloni G,Chon C,Crary J

    更新日期:2018-10-01 00:00:00

  • Neurological evaluation of untreated human immunodeficiency virus infected adults in Ethiopia.

    abstract::Human immunodeficiency virus (HIV) has been implicated in neurological complications in developed countries. Developing countries have different viral clades and potentially different genetic and social risks for these complications. Baseline neurological performance measures associated with HIV infection have rarely ...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280601169837

    authors: Clifford DB,Mitike MT,Mekonnen Y,Zhang J,Zenebe G,Melaku Z,Zewde A,Gessesse N,Wolday D,Messele T,Teshome M,Evans S

    更新日期:2007-01-01 00:00:00

  • The latency-related gene encoded by bovine herpesvirus 1 can suppress caspase 3 and caspase 9 cleavage during productive infection.

    abstract::When the bovine herpesvirus 1 (BHV-1) latency-related (LR) gene is inserted into the latency-associated transcript (LAT) locus of a herpes simplex virus type 1 (HSV-1) LAT deletion mutant, high levels of spontaneous reactivation from latency and enhanced pathogenesis occur. The LR gene, but not LAT, inhibits caspase 3...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280490261716

    authors: Henderson G,Perng GC,Nesburn AB,Wechsler SL,Jones C

    更新日期:2004-02-01 00:00:00

  • Regulation of caspase 8- and caspase 9-induced apoptosis by the herpes simplex virus type 1 latency-associated transcript.

    abstract::The latency-associated transcript (LAT) is the only herpes simplex virus type 1 (HSV-1) gene that is abundantly transcribed during latency. Plasmids expressing LAT inhibit apoptosis induced by etoposide and ceramide in transiently transfected cells. LAT also inhibits apoptosis in trigeminal ganglia of rabbits and prom...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280290101085

    authors: Henderson G,Peng W,Jin L,Perng GC,Nesburn AB,Wechsler SL,Jones C

    更新日期:2002-12-01 00:00:00

  • The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) protects cells against cold-shock-induced apoptosis by maintaining phosphorylation of protein kinase B (AKT).

    abstract::The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) blocks apoptosis and inhibits caspase-3 activation. We previously showed that serum starvation (removal of serum from tissue culture media), which takes several days to induce apoptosis, results in decreased levels of both AKT (protein kinase ...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-015-0361-z

    authors: Carpenter D,Hsiang C,Jiang X,Osorio N,BenMohamed L,Jones C,Wechsler SL

    更新日期:2015-10-01 00:00:00

  • Diagnosis and clinical management of neurological disorders caused by cytomegalovirus in AIDS patients. European Union Concerted Action on Virus Meningitis and Encephalitis.

    abstract::Cytomegalovirus (CMV) infections are common and severe complications of HIV infection. The virus involves the nervous system, causing encephalitis, polyradiculomyelitis and peripheral neuropathies. Due to their limited sensitivity, traditional virological approaches, such as virus isolation or antigen detection in the...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章,评审

    doi:10.3109/13550289809113490

    authors: Cinque P,Cleator GM,Weber T,Monteyne P,Sindic C,Gerna G,van Loon AM,Klapper PE

    更新日期:1998-02-01 00:00:00

  • Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies.

    abstract::Rabies is a neurological disease with 100% lethality. Some of the rare human patients who survived after multiple drug treatment had severe sequelae. The present study showed that after 48 h of RABV inoculation, mice injected intracerebrally with anti-RABV F (ab')2 plus Bioporter® showed 70% survival compared to the c...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1007/s13365-020-00883-8

    authors: Agostinho WC,Brandão PE

    更新日期:2020-10-01 00:00:00

  • Characterization of antibodies raised against bovine-PrP-peptides.

    abstract::To analyze the antigenicity of peptides derived from bovine prion protein (PrP) cDNA, we immunized rabbits with four synthetic peptides and compared the immunoreactivity of antibodies to PrPs from various species by immunoblotting and immunohistochemistry. Two of the antibodies reacted strongly with all PrPs. The othe...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.3109/13550289909015816

    authors: Takahashi H,Takahashi RH,Hasegawa H,Horiuchi M,Shinagawa M,Yokoyama T,Kimura K,Haritani M,Kurata T,Nagashima K

    更新日期:1999-06-01 00:00:00

  • Murine hepatitis virus--a model for virus-induced CNS demyelination.

    abstract::Most murine hepatitis virus (MHV) strains, as their name suggests, infect the liver. However, several murine strains are tropic for the central nervous system (CNS) and cause encephalitis with subsequent CNS demyelination. The CNS demyelination shares pathological similarities with human CNS demyelinating diseases suc...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章,评审

    doi:10.1080/13550280290049534

    authors: Matthews AE,Weiss SR,Paterson Y

    更新日期:2002-04-01 00:00:00

  • Herpes simplex virus type 1 and Alzheimer's disease: the autophagy connection.

    abstract::The causes of Alzheimer's disease (AD) and of the characteristic pathological features - amyloid plaques and neurofibrillary tangles - of AD brain are unknown, despite the enormous resources provided over the years for their investigation. Indeed, the only generally accepted risk factors are age, Down syndrome, carria...

    journal_title:Journal of neurovirology

    pub_type: 杂志文章

    doi:10.1080/13550280701802543

    authors: Itzhaki RF,Cosby SL,Wozniak MA

    更新日期:2008-01-01 00:00:00