{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:20:46Z","timestamp":1776860446544,"version":"3.51.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Since only a few studies have been conducted on the factors associated with different HIV-1 tropisms in low-level viral load HIV-1 infections in China, we investigated the sequences of HIV-1 V3 loop in prevalent HIV-1 subtypes and factors related to HIV-1 tropism and immune recovery in HIV-1 infections after 6 months of highly active antiretroviral therapy (HAART) in Guangdong, China.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma samples with HIV-1 RNA of 400\u2013999 copies\/mL were collected. We analyzed the amino acid sequence of the V3 loop by <jats:italic>in silico<\/jats:italic> prediction algorithms. Mann\u2013Whitney and Chi-square tests were used for statistical comparison. Furthermore, logistic regression and multiple linear regression were used, respectively, for factors associated with 351 HIV-1 tropism and immune recovery of 67 cases with continued CD4<jats:sup>+<\/jats:sup> T cell count during HAART.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a lower percentage of HIV-1 R5-tropic virus in CRF01_AE (66.3%) (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001) and CRF55_01B (52.6%) (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001) compared with both CRF07_BC (96.1%) and CRF08_BC (97.4%), respectively. Compared with the R5-tropic virus, higher proportions of IIe8\/Val8, Arg11\/Lys11, and Arg18\/His18\/Lys18 were observed in the X4-tropic virus of CRF01_AE and CRF07_BC (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001). The baseline CD4<jats:sup>+<\/jats:sup> T cell count (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001) and baseline CD4<jats:sup>+<\/jats:sup> T\/CD8<jats:sup>+<\/jats:sup> T ratio (<jats:italic>p<\/jats:italic>\u2009=\u20090.0006) of all R5-tropic infections were higher than those in the X4-tropic infection. The baseline CD4<jats:sup>+<\/jats:sup> T cell count (odds ratio [OR] 0.9963, <jats:italic>p<\/jats:italic>\u2009=\u20090.0097), CRF07_BC (OR 0.1283, <jats:italic>p<\/jats:italic>\u2009=\u20090.0002), and CRF08_BC (OR 0.1124, <jats:italic>p<\/jats:italic>\u2009=\u20090.0381) were associated with less HIV-1 X4-tropism. The baseline CD4<jats:sup>+<\/jats:sup> T cell count was a positive factor (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001) in the recovery of CD4<jats:sup>+<\/jats:sup> T cell count during HAART.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>R5-tropism represented the majority in low-level viral load HIV-1 infections receiving HAART for more than 6 months in Guangdong, China. The baseline immune level in the HIV-1 R5-tropic infections was higher than that in the X4-tropic infections. The amino acids of the 8th, 11th, and 18th of the HIV-1 V3 loop were more variable in the X4-tropic HIV-1. CRF01_AE, CRF55_01B, and lower baseline CD4<jats:sup>+<\/jats:sup> T cell count were associated with more HIV-1 X4-tropism. The immune recovery during HAART was positively related to baseline CD4<jats:sup>+<\/jats:sup> T cell count.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1159763","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T22:37:00Z","timestamp":1682030220000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["HIV-1 tropism in low-level viral load HIV-1 infections during HAART in Guangdong, China"],"prefix":"10.3389","volume":"14","author":[{"given":"Chuyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiying","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e1008791","DOI":"10.1371\/journal.ppat.1008791","article-title":"Cells producing residual viremia during antiretroviral treatment appear to contribute to rebound viremia following interruption of treatment","volume":"16","author":"Aamer","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1111\/j.1469-0691.2010.03350.x","article-title":"Analysis of co-receptor usage of circulating viral and proviral HIV genome quasispecies by ultra-deep pyrosequencing in patients who are candidates for CCR5 antagonist treatment","volume":"17","author":"Abbate","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1093\/infdis\/jiw172","article-title":"Diversity and tropism of HIV-1 rebound virus populations in plasma level after treatment discontinuation","volume":"214","author":"Bednar","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/34571","article-title":"A new classification for HIV-1","volume":"391","author":"Berger","year":"1998","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.1097\/00002030-200012220-00016","article-title":"Envelope V3 amino acid sequence predicts HIV-1 phenotype (co-receptor usage and tropism for macrophages)","volume":"14","author":"Briggs","year":"2000","journal-title":"AIDS"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e1002106","DOI":"10.1371\/journal.ppat.1002106","article-title":"Detection of inferred CCR5- and CXCR4-using HIV-1 variants and evolutionary intermediates using ultra-deep pyrosequencing","volume":"7","author":"Bunnik","year":"2011","journal-title":"PLoS Pathog."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0014622","DOI":"10.1128\/spectrum.00146-22","article-title":"Enhanced transmissibility and decreased virulence of HIV-1 CRF07_BC may explain its rapid expansion in China","volume":"10","author":"Cheng","year":"2022","journal-title":"Microbiol Spectr"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1097\/QAI.0b013e3181f63906","article-title":"Extreme genetic divergence is required for coreceptor switching in HIV-1 subtype C","volume":"56","author":"Coetzer","year":"2011","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1084\/jem.185.4.621","article-title":"Change in coreceptor use correlates with disease progression in HIV-1--infected individuals","volume":"185","author":"Connor","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1080\/21505594.2021.2004743","article-title":"Persistent low-level viremia in persons living with HIV undertreatment: an unresolved status","volume":"12","author":"Crespo-Bermejo","year":"2021","journal-title":"Virulence"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1097\/01.qai.0000152835.17747.47","article-title":"R5 to X4 switch of the predominant HIV-1 population in cellular reservoirs during effective highly active antiretroviral therapy","volume":"38","author":"Delobel","year":"2005","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1093\/cid\/ciaa413","article-title":"All-cause mortality and serious non-AIDS events in adults with low-level human immunodeficiency virus Viremia during combination antiretroviral therapy: results from a Swedish Nationwide observational study","volume":"72","author":"Elvstam","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1093\/cid\/ciaa380","article-title":"CRF01_AE and CRF01_AE cluster 4 are associated with poor immune recovery in Chinese patients under combination antiretroviral therapy","volume":"72","author":"Ge","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"911806","DOI":"10.3389\/fimmu.2022.911806","article-title":"Unique profile of predominant CCR5-tropic in CRF07_BC HIV-1 infections and discovery of an unusual CXCR4-tropic strain","volume":"13","author":"Hu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1126\/science.1145373","article-title":"Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4","volume":"317","author":"Huang","year":"2007","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1093\/cid\/ciz129","article-title":"Persistent low-level Viremia while on antiretroviral therapy is an independent risk factor for Virologic failure","volume":"69","author":"Joya","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1038\/nbt1371","article-title":"Bioinformatics prediction of HIV coreceptor usage","volume":"25","author":"Lengauer","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"4529","DOI":"10.2147\/IDR.S332924","article-title":"Persistent low-level Viremia is an independent risk factor for Virologic failure: A retrospective cohort study in China","volume":"14","author":"Li","year":"2021","journal-title":"Infect Drug Resist"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.cell.2020.03.005","article-title":"Curing HIV: seeking to target and clear persistent infection","volume":"181","author":"Margolis","year":"2020","journal-title":"Cells"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1001\/jama.293.7.817","article-title":"Intermittent HIV-1 viremia (blips) and drug resistance in patients receiving HAART","volume":"293","author":"Nettles","year":"2005","journal-title":"JAMA"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1097\/QAD.0b013e3283365356","article-title":"Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV","volume":"24","author":"Neuhaus","year":"2010","journal-title":"AIDS"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"473","DOI":"10.3109\/1040841X.2013.867829","article-title":"Effect of HIV-1 subtype and tropism on treatment with chemokine coreceptor entry inhibitors; overview of viral entry inhibition","volume":"41","author":"Panos","year":"2015","journal-title":"Crit. Rev. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e01736-19","DOI":"10.1128\/JVI.01736-19","article-title":"CXCR4-using HIV strains predominate in naive and central memory CD4(+) T cells in people living with HIV on antiretroviral therapy: implications for how latency is established and maintained","volume":"94","author":"Roche","year":"2020","journal-title":"J. Virol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1097\/QAD.0000000000002010","article-title":"CD4+ cell count recovery after combined antiretroviral therapy in the modern combined antiretroviral therapy era","volume":"32","author":"Roul","year":"2018","journal-title":"AIDS"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1002\/jmv.21598","article-title":"Co-receptor switch during HAART is independent of virological success","volume":"81","author":"Saracino","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1186\/1479-5876-9-S1-S5","article-title":"Clinical significance of HIV-1 coreceptor usage","volume":"9","author":"Schuitemaker","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1073\/pnas.1814714116","article-title":"Disparate impact on CD4 T cell count by two distinct HIV-1 phylogenetic clusters from the same clade","volume":"116","author":"Song","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1093\/infdis\/jiq030","article-title":"Deep sequencing to infer HIV-1 co-receptor usage: application to three clinical trials of maraviroc in treatment-experienced patients","volume":"203","author":"Swenson","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1126\/science.1241475","article-title":"Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex","volume":"341","author":"Tan","year":"2013","journal-title":"Science"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"4962","DOI":"10.1128\/JVI.72.6.4962-4969.1998","article-title":"Expression of CCR5 increases during monocyte differentiation and directly mediates macrophage susceptibility to infection by human immunodeficiency virus type 1","volume":"72","author":"Tuttle","year":"1998","journal-title":"J. Virol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1093\/cid\/cix998","article-title":"Multimorbidity among persons living with human immunodeficiency virus in the United States","volume":"66","author":"Wong","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3147","DOI":"10.1128\/JVI.02587-09","article-title":"A V3 loop-dependent gp120 element disrupted by CD4 binding stabilizes the human immunodeficiency virus envelope glycoprotein trimer","volume":"84","author":"Xiang","year":"2010","journal-title":"J. Virol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"7117","DOI":"10.1128\/JVI.73.9.7117-7125.1999","article-title":"Role of CXCR4 in cell-cell fusion and infection of monocyte-derived macrophages by primary human immunodeficiency virus type 1 (HIV-1) strains: two distinct mechanisms of HIV-1 dual tropism","volume":"73","author":"Yi","year":"1999","journal-title":"J. Virol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e1003310","DOI":"10.1371\/journal.ppat.1003310","article-title":"Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism","volume":"9","author":"Zhang","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"7142","DOI":"10.1128\/JVI.00441-16","article-title":"Deep sequencing of the HIV-1 env gene reveals discrete X4 lineages and linkage disequilibrium between X4 and R5 viruses in the V1\/V2 and V3 variable regions","volume":"90","author":"Zhou","year":"2016","journal-title":"J. Virol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1159763\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T22:37:06Z","timestamp":1682030226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1159763\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":35,"alternative-id":["10.3389\/fmicb.2023.1159763"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1159763","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,20]]},"article-number":"1159763"}}