{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:22:27Z","timestamp":1777522947850,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00945"],"award-info":[{"award-number":["PI20\/00945"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/01896"],"award-info":[{"award-number":["PI23\/01896"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union","award":["PI20\/00945"],"award-info":[{"award-number":["PI20\/00945"]}]},{"name":"European Union","award":["PI23\/01896"],"award-info":[{"award-number":["PI23\/01896"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The dynamics of the HIV reservoir during antiretroviral therapy (ART) exhibit variability, with a pronounced decline during the initial years of treatment. However, the identification of biomarkers and host factors associated with the decay of the different forms of HIV proviruses remains to be fully elucidated. We conducted a longitudinal study on people with HIV provided by the Spanish National HIV cohort. We assessed the HIV-DNA levels by Intact Proviral DNA Assay, and inflammatory markers using the Proximity Extension Assay, before and after ART initiation. A multivariate linear regression model was employed to identify potential predictive markers. Our results highlight the identification of novel inflammatory markers, such as ADA, DNER, CDCP1, SCF, among others, that varied significantly over ART initiation. In addition, we observed several markers associated with intact HIV-DNA before ART initiation (CD8A, CX3CL1, and ST1A1) or during undetectable viral load post-ART (IL-10). Moreover, up to five markers were able to predict the intact HIV reservoir decay over ART. The strongest predictor was Stem Cell Factor (SCF), where higher baseline levels of this marker were associated with a greater decline in the intact HIV reservoir. In conclusion, we have identified inflammatory markers associated with the size and dynamics of the HIV-DNA reservoir. These findings provide new insights that could contribute to the development of multi-targeted intervention strategies aimed at modulating or monitoring the HIV reservoir size.<\/jats:p>","DOI":"10.3390\/ijms26178430","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:42:21Z","timestamp":1756485741000},"page":"8430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-3735","authenticated-orcid":false,"given":"Erick","family":"De La Torre Tarazona","sequence":"first","affiliation":[{"name":"Infectious Diseases Department, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5913-364X","authenticated-orcid":false,"given":"Elisa","family":"Moraga","sequence":"additional","affiliation":[{"name":"HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Fons-Contreras","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3523-6071","authenticated-orcid":false,"given":"Ra\u00fal","family":"Vaquer","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9142-812X","authenticated-orcid":false,"given":"Sonsoles","family":"S\u00e1nchez-Palomino","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0770-0355","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Vallejo-Palma","sequence":"additional","affiliation":[{"name":"General Pediatrics and Infectious and Tropical Diseases Department, Hospital La Paz, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-2847","authenticated-orcid":false,"given":"Sergio","family":"Calder\u00f3n-Vicente","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biology, Complutense de Madrid University, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3839-0417","authenticated-orcid":false,"given":"S\u00f2nia","family":"Vicens-Art\u00e9s","sequence":"additional","affiliation":[{"name":"HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-6940","authenticated-orcid":false,"given":"Teresa","family":"Aldamiz-Echevarria","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Clinical Microbiology and Infectious Diseases Service, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianela","family":"Ciudad Sa\u00f1udo","sequence":"additional","affiliation":[{"name":"Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Moreno","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Centro Nacional de Epidemiolog\u00eda, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"Armenteros-Yeguas","sequence":"additional","affiliation":[{"name":"Centro Sanitario Sandoval, Hospital Universitario Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos, 28010 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Tiraboschi","sequence":"additional","affiliation":[{"name":"HIV Unit and Infectious Diseases Service, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3320-9754","authenticated-orcid":false,"given":"Sergio","family":"Reus Ba\u00f1uls","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Hospital General Universitario Dr. Balmis de Alicante, Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante, 03010 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-7377","authenticated-orcid":false,"given":"Jos\u00e9","family":"Alcam\u00ed","sequence":"additional","affiliation":[{"name":"HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-3554","authenticated-orcid":false,"given":"Sergio","family":"Serrano-Villar","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-1094","authenticated-orcid":false,"given":"Santiago","family":"Moreno","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Medicine, Alcal\u00e1 University, 28871 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the CoRIS cohort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1038\/s41591-021-01590-5","article-title":"Research Priorities for an HIV Cure: International AIDS Society Global Scientific Strategy 2021","volume":"27","author":"Deeks","year":"2021","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e317","DOI":"10.1016\/S2352-3018(18)30039-0","article-title":"Barriers and Strategies to Achieve A Cure for HIV","volume":"5","author":"Pitman","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Belmonti, S., Di Giambenedetto, S., and Lombardi, F. (2021). Quantification of Total HIV DNA as a Marker to Measure Viral Reservoir: Methods and Potential Implications for Clinical Practice. Diagnostics, 12.","DOI":"10.3390\/diagnostics12010039"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11904-017-0355-y","article-title":"The Alphabet Soup of HIV Reservoir Markers","volume":"14","author":"Sharaf","year":"2017","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","article-title":"A Quantitative Approach for Measuring the Reservoir of Latent HIV-1 Proviruses","volume":"566","author":"Bruner","year":"2019","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/infdis\/jiaa718","article-title":"Longitudinal Dynamics of Intact HIV Proviral DNA and Outgrowth Virus Frequencies in a Cohort of Individuals Receiving Antiretroviral Therapy","volume":"224","author":"Falcinelli","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11904-025-00723-6","article-title":"Phenotyping Viral Reservoirs to Reveal HIV-1 Hiding Places","volume":"22","author":"Chen","year":"2025","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1097\/QAD.0000000000003065","article-title":"Candidate Host Epigenetic Marks Predictive for HIV Reservoir Size, Responsiveness to Latency Reversal, and Viral Rebound","volume":"35","author":"Corley","year":"2021","journal-title":"AIDS"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41586-022-05538-8","article-title":"Phenotypic Signatures of Immune Selection in HIV-1 Reservoir Cells","volume":"614","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1097\/01.qai.0000131846.12453.29","article-title":"Increased HIV-1 Mucosal Replication is Associated with Generalized Mucosal Cytokine Activation","volume":"37","author":"McGowan","year":"2004","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1337316","DOI":"10.3389\/fimmu.2023.1337316","article-title":"Longitudinal Patterns of Inflammatory Mediators After Acute HIV Infection Correlate to Intact and Total Reservoir","volume":"14","author":"Mortier","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/COH.0000000000000230","article-title":"Residual Inflammation and Viral Reservoirs: Alliance against an HIV Cure","volume":"11","author":"Massanella","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.cytogfr.2012.05.001","article-title":"The Role of Cytokines in the Establishment, Persistence and Eradication of the HIV Reservoir","volume":"23","author":"Vandergeeten","year":"2012","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/infdis\/jiae426","article-title":"Galectin 9 Levels as a Potential Predictor of Intact HIV Reservoir Decay","volume":"231","author":"Gala","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25306","DOI":"10.1038\/s41598-025-09474-1","article-title":"Impact of the Initial Administration of an Antiretroviral Drug with Latency Reversal Properties on the HIV Reservoir Size","volume":"15","author":"Moraga","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/QAD.0000000000001695","article-title":"Wake Me up Before You Go: A Strategy to Reduce the Latent HIV Reservoir","volume":"32","author":"Chomont","year":"2018","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1484358","DOI":"10.3389\/fimmu.2024.1484358","article-title":"Defective Proviruses Significantly Impact Viral Transcription and Immune Activation in Men and Women with HIV-1 Subtype C in Rural South Africa","volume":"15","author":"Buchholtz","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11904-017-0356-x","article-title":"Inflammation, Immune Activation, and Antiretroviral Therapy in HIV","volume":"14","author":"Hileman","year":"2017","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12929-018-0490-9","article-title":"The Effects of Highly Active Antiretroviral Therapy on the Serum Levels of Pro-Inflammatory and Anti-Inflammatory Cytokines in HIV Infected Subjects","volume":"25","author":"Osuji","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1186\/s12967-019-02172-3","article-title":"The Combination of CXCL9, CXCL10 and CXCL11 Levels During Primary HIV Infection Predicts HIV Disease Progression","volume":"17","author":"Yin","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20697","DOI":"10.7448\/IAS.19.1.20697","article-title":"Elevation and Persistence of CD8 T-cells in HIV Infection: The Achilles Heel in the ART Era","volume":"19","author":"Cao","year":"2016","journal-title":"J. Int. AIDS Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"821730","DOI":"10.3389\/fimmu.2022.821730","article-title":"Asymptomatic SARS-CoV-2 Infection Is Associated With Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19","volume":"13","author":"Sauerwald","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2150566","DOI":"10.1080\/22221751.2022.2150566","article-title":"Distinct Inflammation-Related Proteins Associated with T Cell Immune Recovery During Chronic Hiv-1 Infection","volume":"12","author":"Wan","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.molmed.2007.09.001","article-title":"Matrix Metalloproteinase Dysregulation in HIV infection: Implications for Therapeutic Strategies","volume":"13","author":"Mastroianni","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/JVI.02034-13","article-title":"Differential Impact of PD-1 and\/or Interleukin-10 Blockade on HIV-1-Specific CD4 T Cell and Antigen-Presenting Cell Functions","volume":"88","author":"Porichis","year":"2014","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1628086","DOI":"10.3389\/fimmu.2025.1628086","article-title":"No Associations Between HIV Reservoir and Inflammation in Long-Term Virally Suppressed Dolutegravir-Based ART-Treated Individuals","volume":"16","author":"Moutschen","year":"2025","journal-title":"Front. Immunol."},{"key":"ref_27","first-page":"1345","article-title":"Stem cell factor and hematopoiesis","volume":"90","author":"Broudy","year":"1997","journal-title":"Blood J. Am. Soc. Hematol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"664261","DOI":"10.3389\/fcell.2022.664261","article-title":"Hematopoietic Stem Cell Factors: Their Functional Role in Self-Renewal and Clinical Aspects","volume":"10","author":"Mann","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jcv.2011.09.018","article-title":"CD4 T Cell Nadir Independently Predicts the Magnitude of the HIV Reservoir After Prolonged Suppressive Antiretroviral Therapy","volume":"53","author":"Boulassel","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1093\/cid\/ciac249","article-title":"Antiretroviral Initiation at \u2265800 CD4+ Cells\/mm3 Associated With Lower Human Immunodeficiency Virus Reservoir Size","volume":"75","author":"Rasmussen","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.eimc.2011.06.002","article-title":"La cohorte de la red espa\u00f1ola de investigaci\u00f3n en sida y su biobanco: Organizaci\u00f3n, principales resultados y p\u00e9rdidas al seguimiento","volume":"29","author":"Berenguer","year":"2011","journal-title":"Enfermedades Infecc. Microbiol. Cl\u00edn."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:35:40Z","timestamp":1760034940000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178430"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178430","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,29]]}}}