{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T18:00:18Z","timestamp":1784397618682,"version":"3.55.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005274","name":"North-West University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>HIV-1 has well-established mechanisms to disrupt essential pathways in people with HIV, such as inflammation and metabolism. Moreover, diversity of the amino acid sequences in fundamental HIV-1 proteins including Tat and Vif, have been linked to dysregulating these pathways, and subsequently influencing clinical outcomes in people with HIV. However, the relationship between Tat and Vif amino acid sequence variation and specific immune markers and metabolites of the tryptophan-kynurenine (Trp-Kyn) pathway remains unclear. Therefore, this study aimed to investigate the relationship between Tat\/Vif amino acid sequence diversity and Trp-Kyn metabolites (quinolinic acid (QUIN), Trp, kynurenic acid (KA), Kyn and Trp\/Kyn ratio), as well as specific immune markers (sCD163, suPAR, IL-6, NGAL and hsCRP) in <jats:italic>n<\/jats:italic>\u2009=\u200967 South African cART-na\u00efve people with HIV.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sanger sequencing was used to determine blood-derived Tat\/Vif amino acid sequence diversity. To measure Trp-Kyn metabolites, a LC\u2013MS\/MS metabolomics platform was employed using a targeted approach. To measure immune markers, Enzyme-linked immunosorbent assays and the Particle-enhanced turbidimetric assay was used.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>After adjusting for covariates, sCD163 (<jats:italic>p<\/jats:italic>\u2009=\u20090.042) and KA (<jats:italic>p<\/jats:italic>\u2009=\u20090.031) were higher in participants with Tat signatures N24 and R57, respectively, and amino acid variation at position 24 (adj R<jats:sup>2<\/jats:sup>\u2009=\u20090.048, \u03b2\u2009=\u2009-0.416, <jats:italic>p<\/jats:italic>\u2009=\u20090.042) and 57 (adj R<jats:sup>2<\/jats:sup>\u2009=\u20090.166, \u03b2\u2009=\u20090.535, <jats:italic>p<\/jats:italic>\u2009=\u20090.031) of Tat were associated with sCD163 and KA, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These preliminary findings suggest that amino acid variation in Tat may have an influence on underlying pathogenic HIV-1 mechanisms and therefore, this line of work merits further investigation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-024-09874-0","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T12:02:29Z","timestamp":1725883349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The association between HIV-1 Tat and Vif amino acid sequence variation, inflammation and Trp-Kyn metabolism: an exploratory investigation"],"prefix":"10.1186","volume":"24","author":[{"given":"Monray E.","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levanco K.","family":"Asia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zander","family":"Lindeque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esm\u00e9","family":"Jansen van Vuren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"9874_CR1","unstructured":"UNAIDS. In danger: UNAIDS global AIDS update 2022. Joint United Nations Programme on HIV\/AIDS; 2022. Available from: https:\/\/www.unaids.org\/en\/resources\/documents\/2022\/in-danger-global-aids-update."},{"issue":"15","key":"9874_CR2","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1056\/NEJMra0706737","volume":"358","author":"BS Taylor","year":"2008","unstructured":"Taylor BS, Sobieszczyk ME, McCutchan FE, Hammer SM. The challenge of HIV-1 subtype diversity. N Engl J Med. 2008;358(15):1590\u2013602","journal-title":"N Engl J Med"},{"key":"9874_CR3","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1186\/1743-422X-8-401","volume":"8","author":"MZ Yousaf","year":"2011","unstructured":"Yousaf MZ, Zia S, Babar ME, Ashfaq UA. The epidemic of HIV\/AIDS in developing countries; the current scenario in Pakistan. Virol J. 2011;8:401.","journal-title":"Virol J"},{"key":"9874_CR4","doi-asserted-by":"crossref","unstructured":"Asia LK, Jansen Van Vuren E, Williams ME. The influence of viral protein R amino acid substitutions on clinical outcomes in people living with HIV: A systematic review. Eur J Clin Invest. 2023;53(5):e13943.","DOI":"10.1111\/eci.13943"},{"issue":"9","key":"9874_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008813","volume":"16","author":"SW Jin","year":"2020","unstructured":"Jin SW, Mwimanzi FM, Mann JK, Bwana MB, Lee GQ, Brumme CJ, Hunt PW, Martin JN, Bangsberg DR, Ndung\u2019u T, et al. Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5. PLoS Pathog. 2020;16(9): e1008813.","journal-title":"PLoS Pathog"},{"key":"9874_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.biochem.67.1.1","volume":"67","author":"AD Frankel","year":"1998","unstructured":"Frankel AD, Young JA. HIV-1: fifteen proteins and an RNA. Annu Rev Biochem. 1998;67:1\u201325.","journal-title":"Annu Rev Biochem"},{"key":"9874_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-422X-7-82","volume":"7","author":"JM Doolittle","year":"2010","unstructured":"Doolittle JM, Gomez SM. Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens. Virology journal. 2010;7:1\u201315.","journal-title":"Virology journal"},{"key":"9874_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.866611","volume":"13","author":"ME Williams","year":"2022","unstructured":"Williams ME, Cloete R. Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Front Microbiol. 2022;13: 866611.","journal-title":"Front Microbiol"},{"key":"9874_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104701","volume":"136","author":"ME Williams","year":"2020","unstructured":"Williams ME, Zulu SS, Stein DJ, Joska JA, Naud\u00e9 PJW. Signatures of HIV-1 subtype B and C Tat proteins and their effects in the neuropathogenesis of HIV-associated neurocognitive impairments. Neurobiol Dis. 2020;136: 104701.","journal-title":"Neurobiol Dis"},{"issue":"5","key":"9874_CR10","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.chom.2014.09.016","volume":"16","author":"J Demeulemeester","year":"2014","unstructured":"Demeulemeester J, Vets S, Schrijvers R, Madlala P, De Maeyer M, De Rijck J, Ndung\u2019u T, Debyser Z, Gijsbers R. HIV-1 integrase variants retarget viral integration and are associated with disease progression in a chronic infection cohort. Cell Host Microbe. 2014;16(5):651\u201362.","journal-title":"Cell Host Microbe"},{"issue":"4","key":"9874_CR11","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1089\/aid.2022.0022","volume":"39","author":"V Ruhanya","year":"2023","unstructured":"Ruhanya V, Jacobs GB, Paul RH, Joska JA, Seedat S, Nyandoro G, Glashoff RH, Engelbrecht S. HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load. AIDS Res Hum Retroviruses. 2023;39(4):166\u201375.","journal-title":"AIDS Res Hum Retroviruses."},{"issue":"11","key":"9874_CR12","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.1007\/s00705-021-05158-z","volume":"166","author":"B Ensoli","year":"2021","unstructured":"Ensoli B, Moretti S, Borsetti A, Maggiorella MT, Butt\u00f2 S, Picconi O, Tripiciano A, Sgadari C, Monini P, Cafaro A. New insights into pathogenesis point to HIV-1 Tat as a key vaccine target. Arch Virol. 2021;166(11):2955\u201374.","journal-title":"Arch Virol"},{"key":"9874_CR13","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3389\/fcimb.2020.00061","volume":"10","author":"D Ajasin","year":"2020","unstructured":"Ajasin D, Eugenin EA. HIV-1 Tat: Role in Bystander Toxicity. Front Cell Infect Microbiol. 2020;10:61.","journal-title":"Front Cell Infect Microbiol"},{"issue":"7","key":"9874_CR14","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.2174\/1389557511313070008","volume":"13","author":"G Yang","year":"2013","unstructured":"Yang G, Xiong X. Viral infectivity factor: a novel therapeutic strategy to block HIV-1 replication. Mini Rev Med Chem. 2013;13(7):1047\u201355.","journal-title":"Mini Rev Med Chem"},{"issue":"2","key":"9874_CR15","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.virol.2008.10.013","volume":"383","author":"K Schmitt","year":"2009","unstructured":"Schmitt K, Hill MS, Ruiz A, Culley N, Pinson DM, Wong SW, Stephens EB. Mutations in the highly conserved SLQYLA motif of Vif in a simian\u2013human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. Virology. 2009;383(2):362\u201372.","journal-title":"Virology"},{"issue":"10","key":"9874_CR16","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.3390\/v13102004","volume":"13","author":"A Alanazi","year":"2021","unstructured":"Alanazi A, Ivanov A, Kumari N, Lin X, Wang S, Kovalskyy D, Nekhai S. Targeting Tat\u2013TAR RNA Interaction for HIV-1 Inhibition. Viruses. 2021;13(10):2004.","journal-title":"Viruses"},{"issue":"7953","key":"9874_CR17","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/s41586-023-05779-1","volume":"615","author":"Y-L Li","year":"2023","unstructured":"Li Y-L, Langley CA, Azumaya CM, Echeverria I, Chesarino NM, Emerman M, Cheng Y, Gross JD. The structural basis for HIV-1 Vif antagonism of human APOBEC3G. Nature. 2023;615(7953):728\u201333.","journal-title":"Nature"},{"issue":"1","key":"9874_CR18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.2174\/187152612798994939","volume":"12","author":"S Mediouni","year":"2012","unstructured":"Mediouni S, Darque A, Baillat G, Ravaux I, Dhiver C, Tissot-Dupont H, Mokhtari M, Moreau H, Tamalet C, Brunet C, et al. Antiretroviral therapy does not block the secretion of the human immunodeficiency virus tat protein. Infect Disord Drug Targets. 2012;12(1):81\u20136.","journal-title":"Infect Disord Drug Targets"},{"issue":"15","key":"9874_CR19","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1097\/QAD.0b013e32833e515a","volume":"24","author":"S Fourati","year":"2010","unstructured":"Fourati S, Malet I, Binka M, Boukobza S, Wirden M, Sayon S, Simon A, Katlama C, Simon V, Calvez V, et al. Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. AIDS. 2010;24(15):2313\u201321.","journal-title":"AIDS"},{"issue":"7","key":"9874_CR20","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1002\/jmv.27720","volume":"94","author":"ME Williams","year":"2022","unstructured":"Williams ME, Ruhanya V, Paul RH, Ipser JC, Stein DJ, Joska JA, Naud\u00e9 PJW. An investigation of the HIV Tat C31S and R57S mutation on peripheral immune marker levels in South African participants: A pilot study. J Med Virol. 2022;94(7):2936\u20138.","journal-title":"J Med Virol"},{"issue":"3","key":"9874_CR21","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1007\/s13365-022-01073-4","volume":"28","author":"V Ruhanya","year":"2022","unstructured":"Ruhanya V, Jacobs GB, Paul RH, Joska JA, Seedat S, Nyandoro G, Glashoff RH, Engelbrecht S. HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment. J Neurovirol. 2022;28(3):392\u2013403.","journal-title":"J Neurovirol"},{"issue":"7","key":"9874_CR22","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1089\/aid.2008.0299","volume":"25","author":"N Gandhi","year":"2009","unstructured":"Gandhi N, Saiyed Z, Thangavel S, Rodriguez J, Rao K, Nair MP. Differential effects of HIV type 1 clade B and clade C Tat protein on expression of proinflammatory and antiinflammatory cytokines by primary monocytes. AIDS Res Hum Retroviruses. 2009;25(7):691\u20139.","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"11","key":"9874_CR23","doi-asserted-by":"publisher","first-page":"5919","DOI":"10.1128\/JVI.01938-06","volume":"81","author":"GR Campbell","year":"2007","unstructured":"Campbell GR, Watkins JD, Singh KK, Loret EP, Spector SA. Human immunodeficiency virus type 1 subtype C Tat fails to induce intracellular calcium flux and induces reduced tumor necrosis factor production from monocytes. J Virol. 2007;81(11):5919\u201328.","journal-title":"J Virol"},{"issue":"24","key":"9874_CR24","doi-asserted-by":"publisher","first-page":"18319","DOI":"10.1074\/jbc.M110.120840","volume":"285","author":"JK Wong","year":"2010","unstructured":"Wong JK, Campbell GR, Spector SA. Differential induction of interleukin-10 in monocytes by HIV-1 clade B and clade C Tat proteins. J Biol Chem. 2010;285(24):18319\u201325.","journal-title":"J Biol Chem"},{"issue":"1","key":"9874_CR25","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12985-024-02419-6","volume":"21","author":"PT Gotora","year":"2024","unstructured":"Gotora PT, Brown K, Martin DR, van der Sluis R, Cloete R, Williams ME. Impact of subtype C-specific amino acid variants on HIV-1 Tat-TAR interaction: insights from molecular modelling and dynamics. Virology Journal. 2024;21(1):144.","journal-title":"Virology Journal"},{"issue":"1","key":"9874_CR26","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s12879-023-08123-0","volume":"23","author":"PT Gotora","year":"2023","unstructured":"Gotora PT, van der Sluis R, Williams ME. HIV-1 Tat amino acid residues that influence Tat-TAR binding affinity: a scoping review. BMC Infect Dis. 2023;23(1):164.","journal-title":"BMC Infect Dis"},{"issue":"1","key":"9874_CR27","doi-asserted-by":"publisher","first-page":"3308","DOI":"10.1038\/s41598-019-39531-5","volume":"9","author":"AP Ruiz","year":"2019","unstructured":"Ruiz AP, Ajasin DO, Ramasamy S, DesMarais V, Eugenin EA, Prasad VR. A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Sci Rep. 2019;9(1):3308.","journal-title":"Sci Rep"},{"issue":"46","key":"9874_CR28","doi-asserted-by":"publisher","first-page":"35350","DOI":"10.1074\/jbc.M110.173286","volume":"285","author":"Y Iwabu","year":"2010","unstructured":"Iwabu Y, Kinomoto M, Tatsumi M, Fujita H, Shimura M, Tanaka Y, Ishizaka Y, Nolan D, Mallal S, Sata T, et al. Differential anti-APOBEC3G activity of HIV-1 Vif proteins derived from different subtypes. J Biol Chem. 2010;285(46):35350\u20138.","journal-title":"J Biol Chem"},{"key":"9874_CR29","doi-asserted-by":"crossref","unstructured":"Marelli S, Williamson JC, Protasio AV, Naamati A, Greenwood EJ, Deane JE, Lehner PJ, Matheson NJ. Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest. Elife. 2020;9:e53036.","DOI":"10.7554\/eLife.53036"},{"issue":"5","key":"9874_CR30","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.celrep.2019.09.057","volume":"29","author":"DJ Salamango","year":"2019","unstructured":"Salamango DJ, Ikeda T, Moghadasi SA, Wang J, McCann JL, Serebrenik AA, Ebrahimi D, Jarvis MC, Brown WL, Harris RS. HIV-1 Vif Triggers Cell Cycle Arrest by Degrading Cellular PPP2R5 Phospho-regulators. Cell Rep. 2019;29(5):1057-1065.e1054.","journal-title":"Cell Rep"},{"issue":"3","key":"9874_CR31","doi-asserted-by":"publisher","first-page":"ofae111","DOI":"10.1093\/ofid\/ofae111","volume":"11","author":"LK Asia","year":"2024","unstructured":"Asia LK, Van Vuren EJ, Kruger IM, Williams ME. A Pilot Investigation of the Association Between Vpr Amino Acid Substitutions and Peripheral Immune Marker Levels in People With Human Immunodeficiency Virus: Implications for Neurocognitive Impairment. Open Forum Infect Dis. 2024;11(3):ofae111.","journal-title":"Open Forum Infect Dis"},{"issue":"1","key":"9874_CR32","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12985-024-02313-1","volume":"21","author":"LK Asia","year":"2024","unstructured":"Asia LK, Van Vuren EJ, Lindeque Z, Williams ME. A pilot investigation of the association between HIV-1 Vpr amino acid sequence diversity and the tryptophan-kynurenine pathway as a potential mechanism for neurocognitive impairment. Virol J. 2024;21(1):47.","journal-title":"Virol J."},{"issue":"2","key":"9874_CR33","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s10096-023-04728-0","volume":"43","author":"ME Williams","year":"2024","unstructured":"Williams ME. HIV-1 Vif protein sequence variations in South African people living with HIV and their influence on Vif-APOBEC3G interaction. Eur J Clin Microbiol Infect Dis. 2024;43(2):325\u201338.","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"9874_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102682","volume":"53","author":"MJ Gartner","year":"2020","unstructured":"Gartner MJ, Roche M, Churchill MJ, Gorry PR, Flynn JK. Understanding the mechanisms driving the spread of subtype C HIV-1. EBioMedicine. 2020;53: 102682.","journal-title":"EBioMedicine"},{"issue":"1","key":"9874_CR35","doi-asserted-by":"publisher","first-page":"15438","DOI":"10.1038\/srep15438","volume":"5","author":"L Ronsard","year":"2015","unstructured":"Ronsard L, Raja R, Panwar V, Saini S, Mohankumar K, Sridharan S, Padmapriya R, Chaudhuri S, Ramachandran VG, Banerjea AC. Genetic and functional characterization of HIV-1 Vif on APOBEC3G degradation: First report of emergence of B\/C recombinants from North India. Sci Rep. 2015;5(1):15438.","journal-title":"Sci Rep"},{"key":"9874_CR36","doi-asserted-by":"publisher","first-page":"7316456","DOI":"10.1155\/2021\/7316456","volume":"2021","author":"T Lv","year":"2021","unstructured":"Lv T, Cao W, Li T. HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies. J Immunol Res. 2021;2021:7316456.","journal-title":"J Immunol Res"},{"issue":"1","key":"9874_CR37","doi-asserted-by":"publisher","first-page":"16947","DOI":"10.1038\/s41598-018-35271-0","volume":"8","author":"NC Peltenburg","year":"2018","unstructured":"Peltenburg NC, Schoeman JC, Hou J, Mora F, Harms AC, Lowe SH, Bierau J, Bakker JA, Verbon A, Hankemeier T, et al. Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy. Sci Rep. 2018;8(1):16947.","journal-title":"Sci Rep"},{"issue":"2","key":"9874_CR38","first-page":"96","volume":"17","author":"JP Routy","year":"2015","unstructured":"Routy JP, Mehraj V, Vyboh K, Cao W, Kema I, Jenabian MA. Clinical Relevance of Kynurenine Pathway in HIV\/AIDS: An Immune Checkpoint at the Crossroads of Metabolism and Inflammation. AIDS Rev. 2015;17(2):96\u2013106.","journal-title":"AIDS Rev"},{"issue":"4","key":"9874_CR39","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1093\/clinchem\/44.4.858","volume":"44","author":"M Huengsberg","year":"1998","unstructured":"Huengsberg M, Winer JB, Gompels M, Round R, Ross J, Shahmanesh M. Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients. Clin Chem. 1998;44(4):858\u201362.","journal-title":"Clin Chem"},{"key":"9874_CR40","doi-asserted-by":"publisher","first-page":"1244622","DOI":"10.3389\/fimmu.2023.1244622","volume":"14","author":"S Sultana","year":"2023","unstructured":"Sultana S, Elengickal A, Bensreti H. Belin de Chantem\u00e8le E, McGee-Lawrence ME, Hamrick MW: The kynurenine pathway in HIV, frailty and inflammaging. Front Immunol. 2023;14:1244622.","journal-title":"Front Immunol"},{"issue":"6","key":"9874_CR41","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1038\/s41386-020-0607-1","volume":"45","author":"E Haroon","year":"2020","unstructured":"Haroon E, Welle JR, Woolwine BJ, Goldsmith DR, Baer W, Patel T, Felger JC, Miller AH. Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression. Neuropsychopharmacology. 2020;45(6):998\u20131007.","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"9874_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ahj.2009.04.019","volume":"158","author":"K Teo","year":"2009","unstructured":"Teo K, Chow CK, Vaz M, Rangarajan S, Yusuf S. The Prospective Urban Rural Epidemiology (PURE) study: Examining the impact of societal influences on chronic noncommunicable diseases in low-, middle-, and high-income countries. Am Heart J. 2009;158(1):1-7.e1.","journal-title":"Am Heart J"},{"key":"9874_CR43","doi-asserted-by":"publisher","first-page":"117864691986897","DOI":"10.1177\/1178646919868978","volume":"12","author":"AA Badawy","year":"2019","unstructured":"Badawy AA, Guillemin G. The Plasma [Kynurenine]\/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal. Int J Tryptophan Res. 2019;12:1178646919868978.","journal-title":"Int J Tryptophan Res"},{"issue":"1","key":"9874_CR44","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12879-024-09050-4","volume":"24","author":"SE Mabhida","year":"2024","unstructured":"Mabhida SE, McHiza ZJ, Mokgalaboni K, Hanser S, Choshi J, Mokoena H, Ziqubu K, Masilela C, Nkambule BB, Ndwandwe DE, et al. High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis. BMC Infect Dis. 2024;24(1):160.","journal-title":"BMC Infect Dis"},{"issue":"8","key":"9874_CR45","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1093\/infdis\/jiw263","volume":"214","author":"TB Knudsen","year":"2016","unstructured":"Knudsen TB, Ertner G, Petersen J, M\u00f8ller HJ, Moestrup SK, Eugen-Olsen J, Kronborg G, Benfield T. Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1\u2013Infected Individuals. J Infect Dis. 2016;214(8):1198\u2013204.","journal-title":"J Infect Dis"},{"issue":"4","key":"9874_CR46","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1093\/infdis\/jiv123","volume":"212","author":"\u00c1H Borges","year":"2015","unstructured":"Borges \u00c1H, O\u2019Connor JL, Phillips AN, R\u00f6nsholt FF, Pett S, Vjecha MJ, French MA, Lundgren JD. Factors Associated With Plasma IL-6 Levels During HIV Infection. J Infect Dis. 2015;212(4):585\u201395.","journal-title":"J Infect Dis"},{"issue":"4","key":"9874_CR47","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/cid\/ciy966","volume":"69","author":"M Hoenigl","year":"2019","unstructured":"Hoenigl M, Moser CB, Funderburg N, Bosch R, Kantor A, Zhang Y, Eugen-Olsen J, Finkelman M, Reiser J, Landay A, et al. Soluble Urokinase Plasminogen Activator Receptor Is Predictive of Non-AIDS Events During Antiretroviral Therapy-mediated Viral Suppression. Clin Infect Dis. 2019;69(4):676\u201386.","journal-title":"Clin Infect Dis"},{"issue":"4","key":"9874_CR48","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1007\/s11481-019-09870-1","volume":"14","author":"ME Williams","year":"2019","unstructured":"Williams ME, Ipser JC, Stein DJ, Joska JA, Naud\u00e9 PJW. The Association of Immune Markers with Cognitive Performance in South African HIV-Positive Patients. J Neuroimmune Pharmacol. 2019;14(4):679\u201387.","journal-title":"J Neuroimmune Pharmacol"},{"key":"9874_CR49","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1007\/s13365-020-00873-w","volume":"26","author":"ME Williams","year":"2020","unstructured":"Williams ME, Joska JA, Amod AR, Paul RH, Stein DJ, Ipser JC, Naud\u00e9 PJ. The association of peripheral immune markers with brain cortical thickness and surface area in South African people living with HIV. J Neurovirol. 2020;26:908\u201319.","journal-title":"J Neurovirol"},{"issue":"13","key":"9874_CR50","doi-asserted-by":"publisher","first-page":"3784","DOI":"10.1093\/nar\/gkg563","volume":"31","author":"E Gasteiger","year":"2003","unstructured":"Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A. ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 2003;31(13):3784\u20138.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"9874_CR51","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s13365-018-0688-3","volume":"25","author":"MR Keegan","year":"2019","unstructured":"Keegan MR, Winston A, Higgs C, Fuchs D, Boasso A, Nelson M. Tryptophan metabolism and its relationship with central nervous system toxicity in people living with HIV switching from efavirenz to dolutegravir. J Neurovirol. 2019;25(1):85\u201390.","journal-title":"J Neurovirol"},{"issue":"1","key":"9874_CR52","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12929-018-0490-9","volume":"25","author":"FN Osuji","year":"2018","unstructured":"Osuji FN, Onyenekwe CC, Ahaneku JE, Ukibe NR. The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects. J Biomed Sci. 2018;25(1):88.","journal-title":"J Biomed Sci"},{"issue":"6","key":"9874_CR53","doi-asserted-by":"publisher","first-page":"e0158169","DOI":"10.1371\/journal.pone.0158169","volume":"11","author":"A Castley","year":"2016","unstructured":"Castley A, Williams L, James I, Guelfi G, Berry C, Nolan D. Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors. PLoS ONE. 2016;11(6):e0158169\u2013e0158169.","journal-title":"PLoS ONE"},{"issue":"1","key":"9874_CR54","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1097\/QAD.0000000000002378","volume":"34","author":"M Generoso","year":"2020","unstructured":"Generoso M, \u00c1lvarez P, Kravietz A, Mwamzuka M, Marshed F, Ahmed A, Khaitan A. High soluble CD163 levels correlate with disease progression and inflammation in Kenyan children with perinatal HIV-infection. AIDS. 2020;34(1):33\u20138.","journal-title":"AIDS"},{"issue":"3","key":"9874_CR55","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1093\/infdis\/jiw173","volume":"214","author":"\u00c1H Borges","year":"2016","unstructured":"Borges \u00c1H, O\u2019Connor JL, Phillips AN, Neaton JD, Grund B, Neuhaus J, Vjecha MJ, Calmy A, Koelsch KK, Lundgren JD. Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection. J Infect Dis. 2016;214(3):408\u201316.","journal-title":"J Infect Dis"},{"key":"9874_CR56","first-page":"8","volume":"2017","author":"E Wirthgen","year":"1957","unstructured":"Wirthgen E, Hoeflich A, Rebl A, G\u00fcnther J. Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions. Front Immunol. 1957;2017:8.","journal-title":"Front Immunol"},{"issue":"5","key":"9874_CR57","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1128\/JVI.78.5.2586-2590.2004","volume":"78","author":"U Ranga","year":"2004","unstructured":"Ranga U, Shankarappa R, Siddappa NB, Ramakrishna L, Nagendran R, Mahalingam M, Mahadevan A, Jayasuryan N, Satishchandra P, Shankar SK, et al. Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. J Virol. 2004;78(5):2586\u201390.","journal-title":"J Virol"},{"issue":"1","key":"9874_CR58","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/1742-4690-10-61","volume":"10","author":"VR Rao","year":"2013","unstructured":"Rao VR, Neogi U, Talboom JS, Padilla L, Rahman M, Fritz-French C, Gonzalez-Ramirez S, Verma A, Wood C, Ruprecht RM, et al. Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. Retrovirology. 2013;10(1):61.","journal-title":"Retrovirology"},{"issue":"47","key":"9874_CR59","doi-asserted-by":"publisher","first-page":"12190","DOI":"10.1523\/JNEUROSCI.3019-08.2008","volume":"28","author":"W Li","year":"2008","unstructured":"Li W, Huang Y, Reid R, Steiner J, Malpica-Llanos T, Darden TA, Shankar SK, Mahadevan A, Satishchandra P, Nath A. NMDA receptor activation by HIV-Tat protein is clade dependent. J Neurosci. 2008;28(47):12190\u20138.","journal-title":"J Neurosci"},{"issue":"6","key":"9874_CR60","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s13365-014-0293-z","volume":"20","author":"RH Paul","year":"2014","unstructured":"Paul RH, Joska JA, Woods C, Seedat S, Engelbrecht S, Hoare J, Heaps J, Valcour V, Ances B, Baker LM, et al. Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. J Neurovirol. 2014;20(6):627\u201335.","journal-title":"J Neurovirol"},{"issue":"2","key":"9874_CR61","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s13365-016-0503-y","volume":"23","author":"RH Paul","year":"2017","unstructured":"Paul RH, Phillips S, Hoare J, Laidlaw DH, Cabeen R, Olbricht GR, Su Y, Stein DJ, Engelbrecht S, Seedat S, et al. Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. J Neurovirol. 2017;23(2):319\u201328.","journal-title":"J Neurovirol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09874-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-024-09874-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09874-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T12:03:57Z","timestamp":1725883437000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-024-09874-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,9]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["9874"],"URL":"https:\/\/doi.org\/10.1186\/s12879-024-09874-0","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,9]]},"assertion":[{"value":"9 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Health Research Ethics Committee of North-West University, South Africa (NWU-00106\u201322-A1), in compliance with the Declaration of Helsinki. All participants provided informed consent. Participants were provided with detailed information about the study objectives, procedures, potential risks, and benefits. They were informed that participation was voluntary, and they could withdraw from the study at any time without any negative consequences. Confidentiality and anonymity of the participants' data were assured throughout the study. Written informed consent was obtained from each participant, and copies of the consent forms are securely stored at the North-West University, South Africa.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"943"}}