Skip to main content

Advertisement

SpringerLink
Log in

Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Inflammation in people living with HIV (PLWH) correlates with severity of HIV-associated neurocognitive disorders. The objective of this study is to identify blood-based markers of neurocognitive function in a demographic balanced cohort of PLWH. Seven neurocognitive domains were evaluated in 121 seropositive Black/African American, Non-Hispanic White, and White Hispanic men and women using computerized assessments. Associations among standardized neurocognitive function and HIV-related parameters, relevant sociodemographic variables, and inflammation-associated cytokines measured in plasma and cellular supernatants were examined using multivariate and univariate regression models. Outlier and covariate analyses were used to identify and normalize for education level, CD4 T cell count, viral load, CNS and drug abuse comorbidities, which could influence biomarker and neurocognitive function associations. Plasma levels of chemokine (C-C motif) ligand (CCL) 8 significantly associated with memory, complex attention, cognitive flexibility, psychomotor speed, executive function, and processing speed. Plasma tissue inhibitor of metalloproteinases 1 associated with the aforementioned domains except memory and processing speed. In addition, plasma interleukin-23 significantly associated with processing speed and executive function. Analysis of peripheral blood cell culture supernatants revealed no significant markers for neurocognitive function. In this cohort, CD4 T cell count and education level also significantly associated with neurocognitive function. All identified inflammatory biomarkers demonstrated a negative correlation to neurocognitive function. These cytokines have known connections to HIV pathophysiology and are potential biomarkers for neurocognitive function in PLWH with promising clinical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Achhra AC, Mocroft A, Ross MJ, Ryom L, Lucas GM, Furrer H, Neuhaus J, Somboonwit C, Kelly M, Gatell JM, Wyatt CM, International Network for Strategic Initiatives in Global HIVTSSG (2015) Kidney disease in antiretroviral-naive HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med 16(Suppl 1):55–63

    CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson AM, Croteau D, Ellis RJ, Rosario D, Potter M, Guillemin GJ, Brew BJ, Woods SP, Letendre SL (2018) HIV, prospective memory, and cerebrospinal fluid concentrations of quinolinic acid and phosphorylated tau. J Neuroimmunol 319:13–18

    CAS  PubMed  PubMed Central  Google Scholar 

  • Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arya M, Amspoker AB, Lalani N, Patuwo B, Kallen M, Street R, Viswanath K, Giordano TP (2013) HIV testing beliefs in a predominantly Hispanic community health center during the routine HIV testing era: does English language ability matter? AIDS Patient Care STDs 27:38–44

    PubMed  PubMed Central  Google Scholar 

  • Ashutosh CC, Borgmann K, Brew K, Ghorpade A (2012) Tissue inhibitor of metalloproteinases-1 protects human neurons from staurosporine and HIV-1-induced apoptosis: mechanisms and relevance to HIV-1-associated dementia. Cell Death Dis 3:e332

    CAS  PubMed  PubMed Central  Google Scholar 

  • Becher B, Durell BG, Noelle RJ (2003) IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis. J Clin Invest 112:1186–1191

    CAS  PubMed  PubMed Central  Google Scholar 

  • Benedict RH, Mezhir JJ, Walsh K, Hewitt RG (2000) Impact of human immunodeficiency virus type-1-associated cognitive dysfunction on activities of daily living and quality of life. Arch Clin Neuropsychol 15:535–544

    CAS  PubMed  Google Scholar 

  • Brabers NA, Nottet HS (2006) Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia. Eur J Clin Investig 36:447–458

    CAS  Google Scholar 

  • Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, Khoruts A, Larson M, Haase AT, Douek DC (2004) CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200:749–759

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brockman MA, Kwon DS, Tighe DP, Pavlik DF, Rosato PC, Sela J, Porichis F, Le Gall S, Waring MT, Moss K, Jessen H, Pereyra F, Kavanagh DG, Walker BD, Kaufmann DE (2009) IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114:346–356

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burdo TH, Weiffenbach A, Woods SP, Letendre S, Ellis RJ, Williams KC (2013) Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. AIDS 27:1387–1395

    CAS  PubMed  Google Scholar 

  • Burlacu R, Umlauf A, Marcotte TD, Soontornniyomkij B, Diaconu CC, Bulacu-Talnariu A, Temereanca A, Ruta SM, Letendre S, Ene L, Achim CL (2019) Plasma CXCL10 correlates with HAND in HIV-infected women. J Neuro-Oncol

  • Calmy A, Gayet-Ageron A, Montecucco F, Nguyen A, Mach F, Burger F, Ubolyam S, Carr A, Ruxungtham K, Hirschel B, Ananworanich J, Group SS (2009) HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS 23:929–939

    CAS  PubMed  Google Scholar 

  • Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, Peytavin G, Tubiana R, Pialoux G, Katlama C (2010) Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50:773–778

    PubMed  Google Scholar 

  • Chaturvedi M, Molino Y, Sreedhar B, Khrestchatisky M, Kaczmarek L (2014) Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood-brain barrier. Int J Nanomedicine 9:575–588

    PubMed  PubMed Central  Google Scholar 

  • Chen F, Radisky ES, Das P, Batra J, Hata T, Hori T, Baine AM, Gardner L, Yue MY, Bu G, del Zoppo G, Patel TC, Nguyen JH (2013) TIMP-1 attenuates blood-brain barrier permeability in mice with acute liver failure. J Cereb Blood Flow Metab 33:1041–1049

    CAS  PubMed  PubMed Central  Google Scholar 

  • Clifford DB, Ances BM (2013) HIV-associated neurocognitive disorder. Lancet Infect Dis 13:976–986

    PubMed  PubMed Central  Google Scholar 

  • Collazos J, Asensi V, Carton JA (2007) Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART. AIDS 21:835–843

    PubMed  Google Scholar 

  • Corlier F, Hafzalla G, Faskowitz J, Kuller LH, Becker JT, Lopez OL, Thompson PM, Braskie MN (2018) Systemic inflammation as a predictor of brain aging: contributions of physical activity, metabolic risk, and genetic risk. Neuroimage 172:118–129

    PubMed  PubMed Central  Google Scholar 

  • Croxford S, Kitching A, Desai S, Kall M, Edelstein M, Skingsley A, Burns F, Copas A, Brown AE, Sullivan AK, Delpech V (2017) Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort. Lancet Public Health 2:e35–e46

    PubMed  Google Scholar 

  • Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748

    CAS  PubMed  Google Scholar 

  • De Francesco D, Underwood J, Bagkeris E, Anderson J, Williams I, Vera JH, Post FA, Boffito M, Johnson M, PWG M, Winston A, Sabin CA, Pharmacokinetic, Clinical Observations in PeoPle Over fift Ys (2019) Risk factors and impact of patterns of co-occurring comorbidities in people living with HIV. AIDS 33:1871–1880

    PubMed  Google Scholar 

  • Deeks SG, Tracy R, Douek DC (2013) Systemic effects of inflammation on health during chronic HIV infection. Immunity 39:633–645

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dhillon NK, Williams R, Callen S, Zien C, Narayan O, Buch S (2008) Roles of MCP-1 in development of HIV-dementia. Front Biosci 13:3913–3918

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ellis RJ, Badiee J, Vaida F, Letendre S, Heaton RK, Clifford D, Collier AC, Gelman B, McArthur J, Morgello S, McCutchan JA, Grant I, Group C (2011) CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 25:1747–1751

    CAS  PubMed  Google Scholar 

  • Esposito G, Capoccia E, Gigli S, Pesce M, Bruzzese E, D'Alessandro A, Cirillo C, di Cerbo A, Cuomo R, Seguella L, Steardo L, Sarnelli G (2017) HIV-1 Tat-induced diarrhea evokes an enteric glia-dependent neuroinflammatory response in the central nervous system. Sci Rep 7:7735

    PubMed  PubMed Central  Google Scholar 

  • Falasca F, Di Carlo D, De Vito C, Bon I, d'Ettorre G, Fantauzzi A, Mezzaroma I, Fimiani C, Re MC, Vullo V, Antonelli G, Turriziani O (2017) Evaluation of HIV-DNA and inflammatory markers in HIV-infected individuals with different viral load patterns. BMC Infect Dis 17:581

    PubMed  PubMed Central  Google Scholar 

  • Farahani M, Mulinder H, Farahani A, Marlink R (2017) Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis. Int J STD AIDS 28:636–650

    PubMed  Google Scholar 

  • Fernandes JR, Berthoud TK, Kumar A, Angel JB (2017) IL-23 signaling in Th17 cells is inhibited by HIV infection and is not restored by HAART: implications for persistent immune activation. PLoS One 12:e0186823

    PubMed  PubMed Central  Google Scholar 

  • Fish EN (2008) The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 8:737–744

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gandhi RT, McMahon DK, Bosch RJ, Lalama CM, Cyktor JC, Macatangay BJ, Rinaldo CR, Riddler SA, Hogg E, Godfrey C, Collier AC, Eron JJ, Mellors JW, Team AA (2017) Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation. PLoS Pathog 13:e1006285

    PubMed  PubMed Central  Google Scholar 

  • Ghorpade A, Persidskaia R, Suryadevara R, Che M, Liu XJ, Persidsky Y, Gendelman HE (2001) Mononuclear phagocyte differentiation, activation, and viral infection regulate matrix metalloproteinase expression: implications for human immunodeficiency virus type 1-associated dementia. J Virol 75:6572–6583

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gott C, Gates T, Dermody N, Brew BJ, Cysique LA (2017) Cognitive change trajectories in virally suppressed HIV-infected individuals indicate high prevalence of disease activity. PLoS One 12:e0171887

    PubMed  PubMed Central  Google Scholar 

  • Gouwy M, Struyf S, Berghmans N, Vanormelingen C, Schols D, Van Damme J (2011) CXCR4 and CCR5 ligands cooperate in monocyte and lymphocyte migration and in inhibition of dual-tropic (R5/X4) HIV-1 infection. Eur J Immunol 41:963–973

    CAS  PubMed  Google Scholar 

  • Gualtieri CT, Johnson LG (2006) Reliability and validity of a computerized neurocognitive test battery, CNS vital signs. Arch Clin Neuropsychol 21:623–643

    PubMed  Google Scholar 

  • Hair J, Anderson R, Tatham R, Black W (2014) Multivariate data analysis, 7th edn. Pearson Education Limited

  • Hardy DJ, Hinkin CH (2002) Reaction time slowing in adults with HIV: results of a meta-analysis using Brinley plots. Brain Cogn 50:25–34

    PubMed  Google Scholar 

  • Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, Alger J, Singer E, Campbell T, Yiannoutsos C, Cohen R, Navia B, Consortium HIVN (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 25:625–633

    CAS  PubMed  PubMed Central  Google Scholar 

  • Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group C, Group H (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neuro-Oncol 17:3–16

    CAS  Google Scholar 

  • Hinkin CH, Castellon SA, Durvasula RS, Hardy DJ, Lam MN, Mason KI, Thrasher D, Goetz MB, Stefaniak M (2002) Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity. Neurology 59:1944–1950

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hoaglin DC, Welsch RE (1978) The hat matrix in regression and ANOVA. Am Stat 32:17–22

    Google Scholar 

  • Hocini H, Bonnabau H, Lacabaratz C, Lefebvre C, Tisserand P, Foucat E, Lelievre JD, Lambotte O, Saez-Cirion A, Versmisse P, Thiebaut R, Levy Y (2019) HIV Controllers Have Low Inflammation Associated with a Strong HIV-Specific Immune Response in Blood. J Virol:93

  • Ju SM, Song HY, Lee JA, Lee SJ, Choi SY, Park J (2009) Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-kappaB dependent pathway in human astrocytes. Exp Mol Med 41:86–93

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kalayjian RC, Robertson KR, Albert JM, Fichtenbaum CJ, Brown TT, Taiwo BO, Team AS (2019) Plasma Cystatin C associates with HIV-associated neurocognitive disorder but is a poor diagnostic marker in antiretroviral therapy-treated individuals. J Acquir Immune Defic Syndr 81:e49–e54

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kaspar MB, Sterling RK (2017) Mechanisms of liver disease in patients infected with HIV. BMJ Open Gastroenterol 4:e000166

    PubMed  PubMed Central  Google Scholar 

  • Kelder W, McArthur JC, Nance-Sproson T, McClernon D, Griffin DE (1998) Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann Neurol 44:831–835

    CAS  PubMed  Google Scholar 

  • King JE, Eugenin EA, Buckner CM, Berman JW (2006) HIV tat and neurotoxicity. Microbes Infect 8:1347–1357

    CAS  PubMed  Google Scholar 

  • Letendre S (2011) Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med 19:137–142

    PubMed  Google Scholar 

  • Li J, Lau G, Chen L, Yuan YF, Huang J, Luk JM, Xie D, Guan XY (2012) Interleukin 23 promotes hepatocellular carcinoma metastasis via NF-kappa B induced matrix metalloproteinase 9 expression. PLoS One 7:e46264

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liuzzi GM, Mastroianni CM, Santacroce MP, Fanelli M, D'Agostino C, Vullo V, Riccio P (2000) Increased activity of matrix metalloproteinases in the cerebrospinal fluid of patients with HIV-associated neurological diseases. J Neuro-Oncol 6:156–163

    CAS  Google Scholar 

  • Louis S, Dutertre CA, Vimeux L, Fery L, Henno L, Diocou S, Kahi S, Deveau C, Meyer L, Goujard C, Hosmalin A (2010) IL-23 and IL-12p70 production by monocytes and dendritic cells in primary HIV-1 infection. J Leukoc Biol 87:645–653

    CAS  PubMed  Google Scholar 

  • Lyons JL, Uno H, Ancuta P, Kamat A, Moore DJ, Singer EJ, Morgello S, Gabuzda D (2011) Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection. J Acquir Immune Defic Syndr 57:371–379

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maek ANW, Buranapraditkun S, Klaewsongkram J, Ruxrungtham K (2007) Increased interleukin-17 production both in helper T cell subset Th17 and CD4-negative T cells in human immunodeficiency virus infection. Viral Immunol 20:66–75

    Google Scholar 

  • Malhotra P, Haslett P, Sherry B, Shepp DH, Barber P, Abshier J, Roy U, Schmidtmayerova H (2019) Increased plasma levels of the TH2 chemokine CCL18 associated with low CD4+ T cell counts in HIV-1-infected patients with a suppressed viral load. Sci Rep 9:5963

    PubMed  PubMed Central  Google Scholar 

  • Marquine MJ, Flores I, Kamat R, Johnson N, Umlauf A, Letendre S, Jeste D, Grant I, Moore D, Heaton RK (2018) A composite of multisystem injury and neurocognitive impairment in HIV infection: association with everyday functioning. J Neuro-Oncol 24:549–556

    Google Scholar 

  • Mastroianni CM, Liuzzi GM, D'Ettorre G, Lichtner M, Forcina G, Di Campli NF, Riccio P, Vullo V (2002) Matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 in plasma of patients co-infected with HCV and HIV. HIV Clin Trials 3:310–315

    PubMed  Google Scholar 

  • McCarthy CR (1994) Historical background of clinical trials involving women and minorities. Acad Med 69:695–698

    CAS  PubMed  Google Scholar 

  • Merlini E, Bai F, Bellistri GM, Tincati C, d'Arminio Monforte A, Marchetti G (2011) Evidence for polymicrobic flora translocating in peripheral blood of HIV-infected patients with poor immune response to antiretroviral therapy. PLoS One 6:e18580

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mind Exchange Working G (2013) Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program. Clin Infect Dis 56:1004–1017

    Google Scholar 

  • Monnig MA, Kahler CW, Cioe PA, Monti PM, Mayer KH, Pantalone DW, Cohen RA, Ramratnam B (2017) Markers of microbial translocation and immune activation predict cognitive processing speed in heavy-drinking men living with HIV. Microorganisms:5

  • Montoya JL, Campbell LM, Paolillo EW, Ellis RJ, Letendre SL, Jeste DV, Moore DJ (2019) Inflammation relates to poorer complex motor performance among adults living with HIV on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr 80:15–23

    PubMed  PubMed Central  Google Scholar 

  • Morgan AR, Touchard S, Leckey C, O'Hagan C, Nevado-Holgado AJ, Consortium N, Barkhof F, Bertram L, Blin O, Bos I, Dobricic V, Engelborghs S, Frisoni G, Frolich L, Gabel S, Johannsen P, Kettunen P, Kloszewska I, Legido-Quigley C, Lleo A, Martinez-Lage P, Mecocci P, Meersmans K, Molinuevo JL, Peyratout G, Popp J, Richardson J, Sala I, Scheltens P, Streffer J, Soininen H, Tainta-Cuezva M, Teunissen C, Tsolaki M, Vandenberghe R, Visser PJ, Vos S, Wahlund LO, Wallin A, Westwood S, Zetterberg H, Lovestone S, Morgan BP, Annex N-WTCNMD, Alzheimer's D (2019) Inflammatory biomarkers in Alzheimer's disease plasma. Alzheimers Dement 15:776–787

    PubMed  PubMed Central  Google Scholar 

  • Oh SS, Galanter J, Thakur N, Pino-Yanes M, Barcelo NE, White MJ, de Bruin DM, Greenblatt RM, Bibbins-Domingo K, Wu AH, Borrell LN, Gunter C, Powe NR, Burchard EG (2015) Diversity in clinical and biomedical research: a promise yet to be fulfilled. PLoS Med 12:e1001918

    PubMed  PubMed Central  Google Scholar 

  • Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, Kempf DJ, Mellors JW, Coffin JM, King MS (2008) Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 105:3879–3884

    CAS  PubMed  PubMed Central  Google Scholar 

  • Plee J, Le Jan S, Giustiniani J, Barbe C, Joly P, Bedane C, Vabres P, Truchetet F, Aubin F, Antonicelli F, Bernard P (2015) Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome. Sci Rep 5:18001

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rom S, Rom I, Passiatore G, Pacifici M, Radhakrishnan S, Del Valle L, Pina-Oviedo S, Khalili K, Eletto D, Peruzzi F (2010) CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells. FASEB J 24:2292–2300

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ruel TD, Zanoni BC, Ssewanyana I, Cao H, Havlir DV, Kamya M, Achan J, Charlebois ED, Feeney ME (2011) Sex differences in HIV RNA level and CD4 cell percentage during childhood. Clin Infect Dis 53:592–599

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suryadevara R, Holter S, Borgmann K, Persidsky R, Labenz-Zink C, Persidsky Y, Gendelman HE, Wu L, Ghorpade A (2003) Regulation of tissue inhibitor of metalloproteinase-1 by astrocytes: links to HIV-1 dementia. Glia 44:47–56

    PubMed  Google Scholar 

  • Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, Benjamin EJ, Au R, Kiel DP, Wolf PA, Seshadri S (2007) Inflammatory markers and the risk of Alzheimer disease: the Framingham study. Neurology 68:1902–1908

    CAS  PubMed  Google Scholar 

  • Taramasso L, Liggieri F, Cenderello G, Bovis F, Giannini B, Mesini A, Giacomini M, Cassola G, Viscoli C, Di Biagio A (2019) Bloodstream infections in patients living with HIV in the modern cART era. Sci Rep 9:5418

    CAS  PubMed  PubMed Central  Google Scholar 

  • UNAIDS (2019) Global HIV & AIDS statistics — 2019 fact sheet

  • Veenstra M, Byrd DA, Inglese M, Buyukturkoglu K, Williams DW, Fleysher L, Li M, Gama L, Leon-Rivera R, Calderon TM, Clements JE, Morgello S, Berman JW (2019) CCR2 on peripheral blood CD14(+)CD16(+) monocytes correlates with neuronal damage, HIV-associated neurocognitive disorders, and peripheral HIV DNA: reseeding of CNS reservoirs? J NeuroImmune Pharmacol 14:120–133

    PubMed  Google Scholar 

  • Vos CM, Gartner S, Ransohoff RM, McArthur JC, Wahl L, Sjulson L, Hunter E, Conant K (2000) Matrix metalloprotease-9 release from monocytes increases as a function of differentiation: implications for neuroinflammation and neurodegeneration. J Neuroimmunol 109:221–227

    CAS  PubMed  Google Scholar 

  • Vos AG, Idris NS, Barth RE, Klipstein-Grobusch K, Grobbee DE (2016) Pro-inflammatory markers in relation to cardiovascular disease in HIV infection. A Systematic Review. PLoS One 11:e0147484

    PubMed  PubMed Central  Google Scholar 

  • Vujkovic-Cvijin I, Somsouk M (2019) HIV and the gut microbiota: composition, consequences, and avenues for amelioration. Curr HIV/AIDS Rep 16:204–213

    PubMed  PubMed Central  Google Scholar 

  • Wang J, Gabuzda D (2006) Reconstitution of human immunodeficiency virus-induced neurodegeneration using isolated populations of human neurons, astrocytes, and microglia and neuroprotection mediated by insulin-like growth factors. J Neuro-Oncol 12:472–491

    CAS  Google Scholar 

  • Wang J, Song Y, Chen Z, Leng SX (2018) Connection between systemic inflammation and neuroinflammation underlies neuroprotective mechanism of several phytochemicals in neurodegenerative diseases. Oxidative Med Cell Longev 2018:1972714

    Google Scholar 

  • World Medical A (2001) World medical association declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Organ 79:373–374

    Google Scholar 

  • Yang OO, Garcia-Zepeda EA, Walker BD, Luster AD (2002) Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5. J Infect Dis 185:1174–1178

    CAS  PubMed  Google Scholar 

  • Yannam GR, Gutti T, Poluektova LY (2012) IL-23 in infections, inflammation, autoimmunity and cancer: possible role in HIV-1 and AIDS. J NeuroImmune Pharmacol 7:95–112

    PubMed  Google Scholar 

  • Yoshimura K (2017) Current status of HIV/AIDS in the ART era. J Infect Chemother 23:12–16

    PubMed  Google Scholar 

Download references

Acknowledgments

We thank the following for their kind assistance with participant recruitment and medical history reviews. Dr. Barbara Atkinson at the Infectious Disease Clinic at UNTHSC and her nurse Ms. Cindy Bishop. Dr. Catherine Colquitt at Tarrant County Public Health Preventive Medicine Clinic, Fort Worth, Texas and her support staff Ms. Deborah Radaford, Ms. Marry Ellen Yarrish, and Ms. Blanca Delatorre. Ms. Victoria Langston at the John Peter Smith (JPS) Healing Wings HIV/AIDS Center, Fort Worth, Texas. All the staff and clinicians at the AIDS Health Care Foundation, Fort Worth, Texas, the AIDS Outreach Center, Fort Worth, Texas, Samaritan House, Fort Worth, Texas, and Tarrant County Infectious Diseases Associates, Fort Worth, Texas. We appreciate the effort of our other study staff. Ms. Satomi Stacy, who served as a research coordinator who collected and processed patient samples. Dr. Manmeet Kaur Mamik, Ms. Lin Tang and the late Dr. Brian Molles for processing patient samples. Several translators facilitated communication with our White Hispanic populations, we thank Ms. Monica Castillo, Ms. Haydee Izurieta Munoz, Mr. Raul Vintimilla, Ms. Adriana Gamboa Guzman and Dr. Ricardo Belmares. Several medical research assistants assisted with data entry and scheduling, Ms. Anjani Pandya, Ms. Samantha Mannala, Mr. Shrunjal Trivedi and Ms. Shriya Sarin. We appreciate the talents of our nurses Ms. Kim Brown, and Ms. Stella Weis who drew blood samples for these studies. And the Ghorpade/Borgmann lab members Ms. Satomi Stacy, Mr. Venkata Viswanadh Edara and Ms. Jessica Proulx for their thorough review and editing of this manuscript.

Funding

This work was funded by the National Institute for Minorities Health and Health Disparities (P20MD006882) to Anuja Ghorpade, Ph.D. (PI Project 2) and the J.E.S. Edwards Foundation of Fort Worth, TX.

Author information

Authors and Affiliations

  1. Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA

    Naomi Swanta, Sangeeta Shenoy, Anuja Ghorpade & Kathleen Borgmann

  2. Department of Biostatistics, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA

    Subhash Aryal

  3. Department of Gynecology Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Subhash Aryal

  4. Department of Pharmacology and Neuroscience, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA

    Vicki Nejtek & Kathleen Borgmann

  5. Medical Innovation Collaborative of North Texas, Irving, TX, USA

    Anuja Ghorpade

Authors
  1. Naomi Swanta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Subhash Aryal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vicki Nejtek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sangeeta Shenoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anuja Ghorpade
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kathleen Borgmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analyses were performed by Naomi Swanta, Kathleen Borgmann, Subhash Aryal, Sangeeta Shenoy, and Anuja Ghorpade. The first draft of the manuscript was written by Naomi Swanta, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kathleen Borgmann.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

Scatterplot matrixes and histograms of neurocognitive standard scores mapped to race and sex. Pairwise scatterplots and histograms coded for (a) race (red = Non-Hispanic White, green = White Hispanic, blue = Black/African American) and (b) sex (red = Men, blue = Women). Psych. Speed = Psychomotor Speed, Executive Funct. = Executive Function. Red box on Cognitive Flexibility and Executive Function histograms for emphasis. (PNG 1468 kb)

High Resolution Image (TIF 1718 kb)

ESM 2

(DOCX 17 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Swanta, N., Aryal, S., Nejtek, V. et al. Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV. J. Neurovirol. 26, 358–370 (2020). https://doi.org/10.1007/s13365-020-00834-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-020-00834-3

Keywords

Search

Navigation