{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:30:13Z","timestamp":1740130213330,"version":"3.37.3"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100016726","name":"AVIRALIA Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016726","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, median (IQR) CD4 count (cells\/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33\u2013211) and 312 (155\u2013517), respectively. Considering HIV-1 tropism, 30.5% had X4\/dual-mixed strains (FPR \u22645%: 22.2%; FPR 5%\u201310%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count &amp;lt;200\u2009cells\/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR \u22645% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to \u22642 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR \u22645%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkab322","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T19:08:35Z","timestamp":1631300915000},"page":"3272-3279","source":"Crossref","is-referenced-by-count":0,"title":["Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease"],"prefix":"10.1093","volume":"76","author":[{"given":"Yagai","family":"Bouba","sequence":"first","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management (CIRCB), Yaound\u00e9, Cameroon"},{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Armenia","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"},{"name":"Saint Camillus International, University of Health Sciences, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Forbici","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, INMI \u2018Lazzaro Spallanzani\u2019-IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ada","family":"Bertoli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"},{"name":"Laboratory of Virology, University Hospital \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanni","family":"Borghi","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, University Hospital, University of Modena and Reggio Emilia, Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Gagliardini","sequence":"additional","affiliation":[{"name":"Clinical Department, INMI \u2018Lazzaro Spallanzani\u2019-IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Vergori","sequence":"additional","affiliation":[{"name":"Clinical Department, INMI \u2018Lazzaro Spallanzani\u2019-IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Cicalini","sequence":"additional","affiliation":[{"name":"Clinical Department, INMI \u2018Lazzaro Spallanzani\u2019-IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Mazzotta","sequence":"additional","affiliation":[{"name":"Clinical Department, INMI \u2018Lazzaro Spallanzani\u2019-IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Malagnino","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases, University Hospital, \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Lichtner","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, \u2018Sapienza\u2019 University, Polo Pontino, Latina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Latini","sequence":"additional","affiliation":[{"name":"Unit of Dermatology and Sexually Transmitted Diseases, San Gallicano Dermatological Institute IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Mussini","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, University Hospital, University of Modena and Reggio Emilia, Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Andreoni","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases, University Hospital, \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"Clinical Department, INMI \u2018Lazzaro Spallanzani\u2019-IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo Federico","family":"Perno","sequence":"additional","affiliation":[{"name":"Bambino Gesu' Children\u2019s Hospital, IRCCS, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ceccherini-Silberstein","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Mercedes","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"2021111722581387000_dkab322-B1","doi-asserted-by":"crossref","first-page":"19756","DOI":"10.7448\/IAS.17.4.19756","article-title":"Resistance remains a problem in treatment failure","volume":"17","author":"Obermeier","year":"2014","journal-title":"J Int AIDS Soc"},{"key":"2021111722581387000_dkab322-B2","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1089\/aid.2019.0063","article-title":"Trends in HIV-1 drug resistance mutations from a U.S. reference laboratory from 2006 to 2017","volume":"35","author":"Kagan","year":"2019","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2021111722581387000_dkab322-B3","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1093\/jac\/dkz554","article-title":"HIV MDR is still a relevant issue despite its dramatic drop over the years","volume":"75","author":"Armenia","year":"2020","journal-title":"J Antimicrob Chemother"},{"year":"2020","key":"2021111722581387000_dkab322-B4"},{"key":"2021111722581387000_dkab322-B5"},{"key":"2021111722581387000_dkab322-B6","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1097\/INF.0000000000001158","article-title":"Phenotypic coreceptor tropism in perinatally HIV-infected youth failing antiretroviral therapy","volume":"35","author":"Agwu","year":"2016","journal-title":"Pediatr Infect Dis J"},{"key":"2021111722581387000_dkab322-B7","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1086\/507312","article-title":"Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients with detectable viremia","volume":"194","author":"Hunt","year":"2006","journal-title":"J Infect Dis"},{"key":"2021111722581387000_dkab322-B8","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1086\/511035","article-title":"HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211","volume":"44","author":"Wilkin","year":"2007","journal-title":"Clin Infect Dis"},{"key":"2021111722581387000_dkab322-B9","doi-asserted-by":"crossref","first-page":"e255\u20137","DOI":"10.1097\/INF.0b013e3182684d8e","article-title":"Prevalence of Transmitted HIV-1 Drug Resistance Mutations in Children and Adolescents in S\u00e3o Paulo, Brazil","volume":"31","author":"Almeida","year":"2012","journal-title":"Pediatr Infect Dis J"},{"key":"2021111722581387000_dkab322-B10","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jcv.2014.04.004","article-title":"Prevalence of R5 and X4 HIV variants in antiretroviral treatment experienced patients with virologic failure","volume":"60","author":"Ferrer","year":"2014","journal-title":"J Clin Virol"},{"key":"2021111722581387000_dkab322-B11","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/jmv.20900","article-title":"Prevalence of X4 tropic HIV-1 variants in patients with differences in disease stage and exposure to antiretroviral therapy","volume":"79","author":"Poveda","year":"2007","journal-title":"J Med Virol"},{"key":"2021111722581387000_dkab322-B12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1310\/hct1501-45","article-title":"Genotypic determination of HIV tropism in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy","volume":"15","author":"Di Biagio","year":"2014","journal-title":"HIV Clin Trials"},{"key":"2021111722581387000_dkab322-B13","first-page":"1048","article-title":"High prevalence of X4\/DM-tropic variants in children and adolescents infected with HIV-1 by vertical transmission","volume":"31","author":"Briz","year":"2012","journal-title":"Pediatr Infect Dis J"},{"key":"2021111722581387000_dkab322-B14","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1089\/aid.2011.0106","article-title":"Drug resistance and coreceptor usage in HIV type 1 subtype C-infected children initiating or failing highly active antiretroviral therapy in South Africa","volume":"28","author":"Green","year":"2012","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2021111722581387000_dkab322-B15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S2055-6640(20)30505-7","article-title":"HIV-1 co-receptor tropism and disease progression in children and young adults with perinatally acquired HIV-1 infection. The HICCUP Study","volume":"1","author":"Foster","year":"2015","journal-title":"J Virus Erad"},{"key":"2021111722581387000_dkab322-B16","first-page":"385","article-title":"The epidemiology of HIV coreceptor tropism","volume":"12","author":"Hoffman","year":"2007","journal-title":"Eur J Med Res"},{"key":"2021111722581387000_dkab322-B17","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1086\/587660","article-title":"The impact of HIV tropism on decreases in CD4 cell count, clinical progression, and subsequent response to a first antiretroviral therapy regimen","volume":"46","author":"Waters","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2021111722581387000_dkab322-B18","doi-asserted-by":"crossref","first-page":"E289","DOI":"10.1111\/j.1469-0691.2012.03905.x","article-title":"The lowest X4 Geno2Pheno false-positive rate is associated with greater CD4 depletion in HIV-1 infected patients","volume":"18","author":"Santoro","year":"2012","journal-title":"Clin Microbiol Infect"},{"key":"2021111722581387000_dkab322-B19","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/cid\/ciu020","article-title":"Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels","volume":"58","author":"Santoro","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2021111722581387000_dkab322-B20","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1093\/jac\/dkv029","article-title":"HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia","volume":"70","author":"Armenia","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2021111722581387000_dkab322-B21","first-page":"195","article-title":"Performance of genotypic tropism testing in clinical practice using the enhanced sensitivity version of Trofile as reference assay: results from the OSCAR Study Group","volume":"33","author":"Svicher","year":"2010","journal-title":"New Microbiol"},{"key":"2021111722581387000_dkab322-B22","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1473-3099(10)70319-4","article-title":"European guidelines on the clinical management of HIV-1 tropism testing","volume":"11","author":"Vandekerckhove","year":"2011","journal-title":"Lancet Infect Dis"},{"key":"2021111722581387000_dkab322-B23","doi-asserted-by":"crossref","first-page":"e53603","DOI":"10.1371\/journal.pone.0053603","article-title":"The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing","volume":"8","author":"Svicher","year":"2013","journal-title":"PLoS One"},{"key":"2021111722581387000_dkab322-B24","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1093\/cid\/cir493","article-title":"Deep third variable sequencing for HIV type 1 tropism in treatment-naive patients: a reanalysis of the MERIT trial of maraviroc","volume":"53","author":"Swenson","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2021111722581387000_dkab322-B25","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1097\/QAD.0b013e32833e6cfb","article-title":"Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies","volume":"24","author":"McGovern","year":"2010","journal-title":"AIDS"},{"key":"2021111722581387000_dkab322-B26","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/QAI.0b013e31826249cf","article-title":"Population-based sequencing of the V3-loop can predict the virological response to maraviroc in treatment-naive patients of the MERIT trial","volume":"61","author":"McGovern","year":"2012","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2021111722581387000_dkab322-B27","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/hiv.12640","article-title":"Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016","volume":"19","author":"Rossetti","year":"2018","journal-title":"HIV Med"},{"author":"Armenia","key":"2021111722581387000_dkab322-B28"},{"key":"2021111722581387000_dkab322-B29","doi-asserted-by":"crossref","first-page":"104534","DOI":"10.1016\/j.jcv.2020.104534","article-title":"Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings","volume":"130","author":"Armenia","year":"2020","journal-title":"J Clin Virol"},{"key":"2021111722581387000_dkab322-B30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/hiv.12388","article-title":"Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens","volume":"18","author":"Armenia","year":"2017","journal-title":"HIV Med"},{"key":"2021111722581387000_dkab322-B31","doi-asserted-by":"crossref","first-page":"e5222","DOI":"10.1097\/MD.0000000000005222","article-title":"Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression","volume":"95","author":"Castagna","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"2021111722581387000_dkab322-B32","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1186\/s12879-019-4047-7","article-title":"Clinical impact of tropism testing in a real-life cohort of HIV infected patients: a retrospective observational study","volume":"19","author":"Deconinck","year":"2019","journal-title":"BMC Infect Dis"},{"key":"2021111722581387000_dkab322-B33","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1093\/jac\/dks455","article-title":"Role and evolution of viral tropism in patients with advanced HIV disease receiving intensified initial regimen in the ANRS 130 APOLLO trial","volume":"68","author":"Charpentier","year":"2013","journal-title":"J Antimicrob Chemother"},{"key":"2021111722581387000_dkab322-B34","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1093\/jac\/dku255","article-title":"Evolution of HIV-1 tropism at quasispecies level after 5 years of combination antiretroviral therapy in patients always suppressed or experiencing episodes of virological failure","volume":"69","author":"Rozera","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2021111722581387000_dkab322-B35","doi-asserted-by":"crossref","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":"2021111722581387000_dkab322-B36","first-page":"125","article-title":"How HIV changes its tropism: evolution and adaptation?","volume":"4","author":"Mosier","year":"2009","journal-title":"Curr Opin HIV AIDS"},{"key":"2021111722581387000_dkab322-B37","doi-asserted-by":"crossref","first-page":"104755","DOI":"10.1016\/j.jcv.2021.104755","article-title":"Adapting the geno2pheno[coreceptor] tool to HIV-1 subtype CRF01_AE by phenotypic validation using clinical isolates from South-East Asia","volume":"136","author":"Marty","year":"2021","journal-title":"J Clin Virol"},{"key":"2021111722581387000_dkab322-B38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/aid.2013.0267","article-title":"Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa","volume":"30","author":"Ketseoglou","year":"2014","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2021111722581387000_dkab322-B39","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/QAI.0b013e318228667f","article-title":"Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa. Implications for future treatment options","volume":"58","author":"Singh","year":"2011","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2021111722581387000_dkab322-B40","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1128\/JVI.01444-07","article-title":"Subtype-specific conformational differences within the V3 region of subtype B and subtype C human immunodeficiency virus type 1 Env Proteins","volume":"82","author":"Patel","year":"2008","journal-title":"J Virol"},{"key":"2021111722581387000_dkab322-B41","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1177\/0956462414546917","article-title":"The utility of genotypic tropism testing in clinical practice","volume":"26","author":"Wyatt","year":"2015","journal-title":"Int J STD AIDS"},{"key":"2021111722581387000_dkab322-B42","doi-asserted-by":"crossref","first-page":"112819","DOI":"10.1016\/j.ejmech.2020.112819","article-title":"Advances of CCR5 antagonists: from small molecules to macromolecules","volume":"208","author":"Qi","year":"2020","journal-title":"Eur J Med Chem"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/76\/12\/3272\/41136437\/dkab322.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/76\/12\/3272\/41136437\/dkab322.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:05:26Z","timestamp":1673222726000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/12\/3272\/6371310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,9,16]]},"published-print":{"date-parts":[[2021,11,12]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab322","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"type":"print","value":"0305-7453"},{"type":"electronic","value":"1460-2091"}],"subject":[],"published-other":{"date-parts":[[2021,12,1]]},"published":{"date-parts":[[2021,9,16]]}}}