{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:05Z","timestamp":1785402185874,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babes University of Medicine and Pharmacy Timisoara"},{"id":[{"id":"https:\/\/ror.org\/00afdp487","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Despite the success of modern antiretroviral therapy in achieving virological suppression, people living with HIV face an elevated risk of cardiovascular diseases, particularly heart failure with preserved ejection fraction. This study evaluates the cardiometabolic phenotype and functional capacity in a Romanian HIV cohort to delineate the metabolic footprint of chronic infection. In this cross-sectional study based on prospectively collected, protocol-driven phenotyping, we evaluated 50 consecutive outpatients from a university-affiliated infectious diseases clinic in Timisoara. Eligibility strictly required clinical stability and sustained virological suppression (plasma HIV-RNA &lt; 50 copies\/mL for \u226512 months). The analysis revealed widespread metabolic dysregulation, with 52% exhibiting excess weight and 64% showing atherogenic dyslipidemia. Integrase strand transfer inhibitor-based regimens were significantly correlated with an increased body mass index (p = 0.034) and elevated LDL cholesterol (aOR = 2.4, 95% CI [1.18\u20134.95], p = 0.022). Furthermore, we observed a pronounced metabolic age gap (+4.5 \u00b1 2.8 years), defined as the deviation of bioimpedance-estimated metabolic age from the patients\u2019 chronological age. This gap (p = 0.028), alongside historical immunodeficiency indicated by a low nadir CD4+ count (aOR = 0.998, 95% CI [0.991\u20130.999], p = 0.021), strongly predicted exercise intolerance, independent of current immune reconstruction. Sarcopenic obesity (present in 18% of the cohort) and an elevated triglycerides-to-HDL ratio (aOR = 2.14, 95% CI [1.15\u20133.98], p = 0.016) emerged as robust independent negative predictors of functional capacity. Additionally, subclinical myocardial remodeling, evidenced by impaired Global Longitudinal Strain, significantly predicted reduced aerobic capacity (aOR = 0.72, 95% CI [0.58\u20130.89], p = 0.003). Consequently, contemporary HIV management must transition beyond virological control to integrated cardiometabolic screening. Utilizing cardiopulmonary exercise testing, echocardiography, and metabolic biomarkers is critical for the early identification of subclinical \u201cfunctional HIV-associated frailty\u201d and mitigating the trajectory toward overt cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/ijms27156733","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"6733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiopulmonary Performance and Subclinical Myocardial Remodeling in Virologically Suppressed HIV Patients: The Role of the Metabolic Age Gap"],"prefix":"10.3390","volume":"27","author":[{"given":"Ioana-Melinda","family":"Luput-Andrica","sequence":"first","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina-Raluca","family":"Marinescu","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-4407","authenticated-orcid":false,"given":"Talida-Georgiana","family":"Cut","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Center for Ethics in Human Genetic Identification, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Herlo","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra","family":"Laza","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Iulian","family":"Oancea","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Pneumology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Center for Research and Innovation in Precision Medicine of Respiratory Diseases (CRIPMRD), Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susa","family":"Septimiu-Radu","sequence":"additional","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Emergency Clinical Hospital Timisoara, Str. Dr. Iosif Nemoianun Nr. 2, 300011 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Simina","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Faculty of Physical Education and Sports, Department of Physiotherapy, West University of Timi\u0219oara, Bulevardul Vasile P\u00e2rvan 4, 300223 Timisoara, Romania"},{"name":"Neoclinic Medical Center, Calea Doroban\u021bilor 3, 307200 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-3714","authenticated-orcid":false,"given":"Camelia Corina","family":"Pescaru","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Pneumology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"},{"name":"Center for Research and Innovation in Precision Medicine of Respiratory Diseases (CRIPMRD), Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voichita Elena","family":"Lazureanu","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S1473-3099(21)00448-5","article-title":"Global Burden and Trends of Sexually Transmitted Infections from 1990 to 2019: An Observational Trend Study","volume":"22","author":"Zheng","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","unstructured":"(2026, February 20). Global HIV & AIDS Statistics\u2014Fact Sheet. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_3","unstructured":"(2026, January 14). HIV Data and Statistics. Available online: https:\/\/www.who.int\/teams\/global-hiv-hepatitis-and-stis-programmes\/hiv\/strategic-information\/hiv-data-and-statistics."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/0735-1097(89)90277-5","article-title":"Cardiac Complications in Acquired Immunodeficiency Syndrome (AIDS): A Review","volume":"13","author":"Acierno","year":"1989","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"691","DOI":"10.7326\/0003-4819-107-5-691","article-title":"Congestive cardiomyopathy and illness related to the acquired immunodeficiency syndrome (AIDS) associated with isolation of retrovirus from myocardium","volume":"107","author":"Calabrese","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"311","DOI":"10.7326\/0003-4819-116-4-311","article-title":"Cardiomyopathy associated with antiretroviral therapy in patients with HIV infection: A report of six cases","volume":"116","author":"Herskowitz","year":"1992","journal-title":"Ann. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"386","author":"Vos","year":"2015","journal-title":"Lancet"},{"key":"ref_8","unstructured":"Freiberg, M.S.C.C., Oursler, K.K., Gottdiener, J., Gottlieb, S., Warner, A., Leaf, D., Rodriguez-Barradas, M.C., Felter, S., and Butt, A.A. (2013, January 3\u20136). The risk of and survival with preserved vs reduced ejection fraction heart failure by HIV status. Proceedings of the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, GA, USA."},{"key":"ref_9","unstructured":"WHO (2026, May 01). HIV\u2014Number of People Dying from HIV-Related Causes. Available online: https:\/\/www.who.int\/data\/gho\/data\/indicators\/indicator-details\/GHO\/number-of-deaths-due-to-hiv-aids."},{"key":"ref_10","unstructured":"(2026, May 01). High-Level Meeting on AIDS. Available online: https:\/\/www.unaids.org\/en\/2026-high-level-meeting-aids."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Luput-Andrica, I.-M., Marinescu, A.-R., Cut, T.-G., Herlo, A., Laza, R., Saizu, A.-E., Floruncut, A.-C., Nicolescu, N., Jumanca, R., and Rosoha, D.-I. (2026). Premature Skeletal Aging and Immunological Recovery in Romanian PLWH: A Cross-Sectional Analysis of Gender-Specific and Metabolic Risk Factors. IJMS, 27.","DOI":"10.3390\/ijms27094079"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Luput-Andrica, I.-M., Marinescu, A.-R., Cut, T.G., Herlo, A., Herlo, L.-F., Saizu, A.-E., Laza, R., Lustrea, A., Floruncut, A.-C., and Chisalita, A. (2025). Evaluation of Bone Mineral Density and Related Factors in Romanian HIV-Positive Patients Undergoing Antiretroviral Therapy. Microorganisms, 13.","DOI":"10.3390\/microorganisms13081768"},{"key":"ref_13","first-page":"303","article-title":"A formula to estimate the approximate surface area if height and weight be known. 1916","volume":"5","author":"DuBois","year":"1989","journal-title":"Nutrition"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Preda, M., and Manolescu, L.C.S. (2022). Romania, a Harbour of HIV-1 Subtype F1: Where Are We After 33 Years of HIV-1 Infection?. Viruses, 14.","DOI":"10.3390\/v14092081"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0140-6736(91)90386-4","article-title":"HIV and Romania","volume":"338","author":"Danescu","year":"1991","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"198","DOI":"10.18683\/germs.2019.1178","article-title":"Consensus Statement on the Assessment of Comorbidities in People Living with HIV in Romania","volume":"9","author":"Mircescu","year":"2019","journal-title":"Germs"},{"key":"ref_17","unstructured":"WHO (2026, March 02). Antiretroviral Therapy for HIV Infection in Adults and Adolescents. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241599764."},{"key":"ref_18","unstructured":"WHO (2026, May 10). Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241549684."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102486","DOI":"10.1016\/j.eclinm.2024.102486","article-title":"The Association of Long-Term Trajectories of BMI, Its Variability, and Metabolic Syndrome: A 30-Year Prospective Cohort Study","volume":"69","author":"Guo","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10476","DOI":"10.24875\/AIDSRev.22000026","article-title":"Antiretroviral Therapy and Weight Gain in Antiretroviral Treatment-Experienced HIV Patients: A Review","volume":"25","author":"Dupont","year":"2023","journal-title":"AIDSRev"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"ofab542","DOI":"10.1093\/ofid\/ofab542","article-title":"Excess Weight Gain with Integrase Inhibitors and Tenofovir Alafenamide: What Is the Mechanism and Does It Matter?","volume":"8","author":"Wood","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jchf.2018.10.006","article-title":"Cardiac Dysfunction Among People Living with HIV","volume":"7","author":"Erqou","year":"2019","journal-title":"JACC Heart Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s11904-019-00458-1","article-title":"Heart Failure among People with HIV: Evolving Risks, Mechanisms, and Preventive Considerations","volume":"16","author":"Toribio","year":"2019","journal-title":"Curr. HIV AIDS Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/0735-1097(89)90256-8","article-title":"Cardiac Manifestations of Human Immunodeficiency Virus Infection: A Two-Dimensional Echocardiographic Study","volume":"13","author":"Himelman","year":"1989","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","first-page":"248","article-title":"Ergospirometry and Echocardiography in Early Stage of Heart Failure with Preserved Ejection Fraction and in Healthy Individuals","volume":"105","author":"Garcia","year":"2015","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1086\/648080","article-title":"Coronary Aging in HIV-Infected Patients","volume":"49","author":"Guaraldi","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.2165\/00003495-200666150-00006","article-title":"Cardiovascular Risk in Patients with HIV Infection: Impact of Antiretroviral Therapy","volume":"66","author":"Bergersen","year":"2006","journal-title":"Drugs"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.10.001","article-title":"Systemic Effects of Inflammation on Health During Chronic HIV Infection","volume":"39","author":"Deeks","year":"2013","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1097\/QAD.0b013e328337afdf","article-title":"Myocardial Infarction Risk in HIV-Infected Patients: Epidemiology, Pathogenesis, and Clinical Management","volume":"24","author":"Calza","year":"2010","journal-title":"AIDS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41569-020-0363-2","article-title":"Evaluation and Management of Heart Failure with Preserved Ejection Fraction","volume":"17","author":"Borlaug","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nrcardio.2017.65","article-title":"Epidemiology of Heart Failure with Preserved Ejection Fraction","volume":"14","author":"Dunlay","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1093\/cvr\/cvac013","article-title":"Global Burden of Heart Failure: A Comprehensive and Updated Review of Epidemiology","volume":"118","author":"Savarese","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1097\/00002030-199809000-00016","article-title":"HIV-1 diversity in Romania","volume":"12","author":"Apetrei","year":"1998","journal-title":"AIDS"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1016\/j.injury.2022.01.047","article-title":"Clinical Practice Guidelines: The Good, the Bad, and the Ugly","volume":"54","author":"Madden","year":"2023","journal-title":"Injury"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_36","unstructured":"WHO (2026, May 25). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6733\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:00:12Z","timestamp":1785225612000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":36,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156733"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156733","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}