{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T22:56:33Z","timestamp":1775688993735,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Mental Health","award":["R01MH094159"],"award-info":[{"award-number":["R01MH094159"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally infected with HIV during childhood. Anti-CMV IgG antibodies were present in 93.7% of participants, with lower levels correlating with longer cART exposure and better immunologic parameters. Patients with immunological treatment success (CD4 &gt; 350 cells\/mL) had significantly lower CMV IgG titers compared to those with suboptimal immune response to cART. In total, 78% of the tested patients had robust CMV-specific T-cell responses, measured by an IFN-\u03b3 release assay. A good immune response to treatment was significantly associated with CMV-specific cellular immunity: IFN-\u03b3 level was positively correlated with CD4 and CD8-T cell counts. No differences were observed between patients with suppressed\/non-suppressed HIV viremia in terms of CMV humoral and cellular immune response. CMV DNA was detected in only 17% of participants, with lower levels among those with cART-induced immune recovery. The successful antiretroviral treatment with subsequent immunologic reconstitution may lead to restoration of CMV-specific immune responses and effective control of latent infection, limiting episodes of CMV reactivation in HIV-positive individuals.<\/jats:p>","DOI":"10.3390\/v17010076","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T07:59:42Z","timestamp":1736409582000},"page":"76","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Combined Antiretroviral Treatment (cART) on Latent Cytomegalovirus Infection"],"prefix":"10.3390","volume":"17","author":[{"given":"Aura","family":"Temereanca","sequence":"first","affiliation":[{"name":"Virology Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Viral Emerging Diseases Department, \u015etefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-8575","authenticated-orcid":false,"given":"Luminita","family":"Ene","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Department, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, 030303 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gratiela","family":"Tardei","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Department, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, 030303 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camelia","family":"Grancea","sequence":"additional","affiliation":[{"name":"Viral Emerging Diseases Department, \u015etefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian L.","family":"Achim","sequence":"additional","affiliation":[{"name":"Pathology Department, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2492-6073","authenticated-orcid":false,"given":"Simona","family":"Ruta","sequence":"additional","affiliation":[{"name":"Virology Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Viral Emerging Diseases Department, \u015etefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/infdis\/jiv148","article-title":"The Sordid Affair Between Human Herpesvirus and HIV","volume":"212","author":"Gianella","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dooley, A.L., and O\u2019Connor, C.M. (2020). Regulation of the MIE Locus During HCMV Latency and Reactivation. Pathogens, 9.","DOI":"10.3390\/pathogens9110869"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., and Di Benedetto, S. (2024). Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020753"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tu, W., and Rao, S. (2016). Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.02111"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/nyas.14994","article-title":"Rethinking human cytomegalovirus latency reservoir","volume":"1524","author":"Schwartz","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1089\/aid.2015.0169","article-title":"The Association of Human Cytomegalovirus with Biomarkers of Inflammation and Immune Activation in HIV-1-Infected Women","volume":"32","author":"Lurain","year":"2016","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12985-018-0937-3","article-title":"Human cytomegalovirus infection and coronary heart disease: A systematic review","volume":"15","author":"Du","year":"2018","journal-title":"Virol. J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Moshomo, T., Molefe-Baikai, O.J., Bennett, K., Gaolathe, T., Moyo, S., Gaseitsewe, S., Mohammed, T., Lockman, S., and Mosepele, M. (2024). Cytomegalovirus Immunoglobulin G Levels and Subclinical Arterial Disease among People Living with HIV in Botswana: A Cross-Sectional Study. Biomedicines, 12.","DOI":"10.3390\/biomedicines12050935"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Heath, J.J., and Michael, D. (2020). The Immune Response Against Human Cytomegalovirus Links Cellular to Systemic Senescence. Cells, 9.","DOI":"10.3390\/cells9030766"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2144","DOI":"10.1002\/rmv.2144","article-title":"Why the elderly appear to be more severely affected by COVID-19: The potential role of immunosenescence and CMV","volume":"30","author":"Kadambari","year":"2020","journal-title":"Rev. Med. Virol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1093\/cid\/ciy170","article-title":"Higher Anti-Cytomegalovirus Immunoglobulin G Concentrations Are Associated With Worse Neurocognitive Performance During Suppressive Antiretroviral Therapy","volume":"67","author":"Letendre","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1097\/QAD.0000000000001412","article-title":"Elevated Cytomegalovirus IgG Antibody Levels Are Associated with HIV-1 Disease Progression and Immune Activation","volume":"31","author":"Patel","year":"2017","journal-title":"AIDS"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/infdis\/jit434","article-title":"Virologic Correlates of Anti-CMV IgG Levels in HIV-1\u2013Infected Men","volume":"209","author":"Gianella","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1089\/aid.2015.0085","article-title":"Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response","volume":"31","author":"Erlandson","year":"2015","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nastri, B.M., Pagliano, P., Zannella, C., Folliero, V., Masullo, A., Rinaldi, L., Galdiero, M., and Franci, G. (2023). HIV and Drug-Resistant Subtypes. Microorganisms, 11.","DOI":"10.3390\/microorganisms11010221"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved Antiviral Drugs over the Past 50 Years","volume":"29","author":"Li","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1097\/00002030-199907090-00008","article-title":"Loss of Cytomegalovirus (CMV) Viraemia Following Highly Active Antiretroviral Therapy in the Absence of Specific Anti-CMV Therapy","volume":"13","author":"Deayton","year":"1999","journal-title":"AIDS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1097\/QAD.0000000000000405","article-title":"Immune Resilience in HIV-Infected Individuals Seronegative for Cytomegalovirus","volume":"28","author":"Barrett","year":"2014","journal-title":"AIDS"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1492","DOI":"10.21769\/BioProtoc.1492","article-title":"Quantification of Total and 2-LTR (Long terminal repeat) HIV DNA, HIV RNA and Herpesvirus DNA in PBMCs","volume":"5","author":"Massanella","year":"2015","journal-title":"Bio-protocol"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Mora, E., Massanella, M., Garc\u00eda, E., Giles, D., Bernad\u00f3, M., Urrea, V., Carrillo, J., Ouchi, D., Puig, J., and Negredo, E. (2017). Elevated Humoral Response to Cytomegalovirus in HIV-Infected Individuals with Poor CD4+ T-Cell Immune Recovery. PLOS ONE, 12.","DOI":"10.1371\/journal.pone.0184433"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jcv.2017.08.016","article-title":"High CMV IgG Antibody Levels Are Associated to a Lower CD4+ RESPONSE to Antiretroviral Therapy in HIV-Infected Women","volume":"96","author":"Giuliano","year":"2017","journal-title":"J. Clin. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.ophtha.2012.11.023","article-title":"Comparison of Treatment Regimens for Cytomegalovirus Retinitis in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy","volume":"120","author":"Jabs","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.ophtha.2015.02.033","article-title":"Studies of the Ocular Complications of AIDS Research Group. Long-term Outcomes of Cytomegalovirus Retinitis in the Era of Modern Antiretroviral Therapy: Results from a United States Cohort","volume":"122","author":"Jabs","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.humimm.2004.02.014","article-title":"CD8+ T-Cell Immunity to Cytomegalovirus","volume":"65","author":"Moss","year":"2004","journal-title":"Hum. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1086\/427828","article-title":"Dynamics of Cytomegalovirus (CMV)\u2013Specific T Cells in HIV-1\u2013Infected Individuals Progressing to AIDS with CMV End-Organ Disease","volume":"191","author":"Bronke","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Naeger, D.M., Martin, J.N., Sinclair, E., Hunt, P.W., Bangsberg, D.R., Hecht, F., Hsue, P., McCune, J.M., and Deeks, S.G. (2010). Cytomegalovirus-Specific T Cells Persist at Very High Levels during Long-Term Antiretroviral Treatment of HIV Disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008886"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/jac\/dkl049","article-title":"Cytomegalovirus (CMV)-specific CD8+ T cells in individuals with HIV infection: Correlation with protection from CMV disease","volume":"57","author":"Stone","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1046\/j.0022-202x.2001.00049.x","article-title":"Immune Reconstitution in HIV-1-Infected Individuals Treated with Potent Antiretroviral Therapy","volume":"6","author":"Connick","year":"2001","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hsu, D.C., Kerr, S.J., Iampornsin, T., Pett, S.L., Avihingsanon, A., Thongpaeng, P., Zaunders, J.J., Ubolyam, S., Ananworanich, J., and Kelleher, A.D. (2013). Restoration of CMV-specific-CD4 T cells with ART occurs early and is greater in those with more advanced immunodeficiency. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077479"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1084\/jem.20042408","article-title":"Repertoire, Diversity, and Differentiation of Specific CD8 T Cells Are Associated with Immune Protection against Human Cytomegalovirus Disease","volume":"201","author":"Sacre","year":"2005","journal-title":"J. Exp. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/1\/76\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:25:18Z","timestamp":1759919118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/1\/76"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["v17010076"],"URL":"https:\/\/doi.org\/10.3390\/v17010076","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]}}}