{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:18:51Z","timestamp":1793233131987,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+\/R+\u2009kidney\u2013liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The donor was a 54\u00a0year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 <jats:italic>env<\/jats:italic> region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12985-021-01730-w","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T13:03:00Z","timestamp":1641474180000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of HIV quasispecies and virological outcome of an HIV D+\/R+ kidney\u2013liver transplantation"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-8268","authenticated-orcid":false,"given":"Gabriella","family":"Rozera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ubaldo","family":"Visco-Comandini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Giombini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Santini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Forbici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Berno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"De Paolis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Colonnelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpiero","family":"D\u2019Offizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Maria","family":"Ettorre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Capobianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ippolito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Abbate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"1730_CR1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.2215\/CJN.05021107","volume":"3","author":"M Abecassis","year":"2008","unstructured":"Abecassis M, Bartlett ST, Collins AJ, Davis CL, Delmonico FL, Friedewald JJ, et al. Kidney transplantation as primary therapy for end-stage renal disease: a national kidney foundation\/kidney disease outcomes quality initiative (NKF\/KDOQI\u2122) conference. Clin J Am Soc Nephrol. 2008;3:471\u201380.","journal-title":"Clin J Am Soc Nephrol"},{"key":"1730_CR2","first-page":"472","volume":"2","author":"H Chiao","year":"2013","unstructured":"Chiao H, Edward Yang C, Frenette CT. Review on liver transplant for hepatocellular carcinoma. Transl Cancer Res. 2013;2:472\u201381.","journal-title":"Transl Cancer Res"},{"key":"1730_CR3","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1093\/cid\/ciu919","volume":"60","author":"AG Abraham","year":"2015","unstructured":"Abraham AG, Althoff KN, Jing Y, Estrella MM, Kitahata MM, Wester W, et al. End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis. 2015;60:941\u20139.","journal-title":"Clin Infect Dis"},{"key":"1730_CR4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/j.1468-1293.2012.01045.x","volume":"14","author":"M Bickel","year":"2013","unstructured":"Bickel M, Marben W, Betz C, Khaykin P, Stephan C, Gute P, et al. End-stage renal disease and dialysis in HIV-positive patients: observations from a long-term cohort study with a follow-up of 22 years. HIV Med. 2013;14:127\u201335.","journal-title":"HIV Med"},{"key":"1730_CR5","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1093\/ndt\/gft289","volume":"29","author":"MG Rasch","year":"2014","unstructured":"Rasch MG, Helleberg M, Feldt-Rasmussen BO, Kronborg G, Larsen CS, Pedersen C, et al. Increased risk of dialysis and end-stage renal disease among HIV patients in Denmark compared with the background population. Nephrol Dial Transplant. 2014;29:1232\u20138.","journal-title":"Nephrol Dial Transplant"},{"key":"1730_CR6","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/ndt\/gfv207","volume":"30","author":"S Razzak Chaudhary","year":"2015","unstructured":"Razzak Chaudhary S, Workeneh BT, Montez-Rath ME, Zolopa AR, Klotman PE, Winkelmayer WC. Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy. Nephrol Dial Transplant. 2015;30:1734\u201340.","journal-title":"Nephrol Dial Transplant"},{"key":"1730_CR7","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1007\/s00705-020-04716-1","volume":"165","author":"R Rashti","year":"2020","unstructured":"Rashti R, Alavian SM, Moradi Y, Sharafi H, Bolbanabad AM, Roshani D, et al. Global prevalence of HCV and\/or HBV coinfections among people who inject drugs and female sex workers who live with HIV\/AIDS: a systematic review and meta-analysis. Arch Virol. 2020;165:1947\u201358.","journal-title":"Arch Virol"},{"key":"1730_CR8","doi-asserted-by":"publisher","first-page":"652672","DOI":"10.3389\/fsoc.2021.652672","volume":"6","author":"CJ Bergo","year":"2021","unstructured":"Bergo CJ, Epstein JR, Hoferka S, Kolak MA, Pho MT. A vulnerability assessment for a future HIV outbreak associated with injection drug use in Illinois, 2017\u20132018. Front Sociol. 2021;6:652672.","journal-title":"Front Sociol"},{"key":"1730_CR9","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s11901-020-00541-x","volume":"19","author":"N Kim","year":"2020","unstructured":"Kim N. Chronic hepatitis B and co-infection chronic hepatitis B and HIV coinfection: a continuing challenge in the era of antiretroviral therapy. Curr Hepatol Rep. 2020;19:345\u201353.","journal-title":"Curr Hepatol Rep"},{"key":"1730_CR10","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000002973","author":"V Guardigni","year":"2021","unstructured":"Guardigni V, Toschi A, Badia L, del Turco ER, Salsi E, Cristini F, et al. Patients living with HIV and cirrhosis the risk for hepatocellular carcinoma after direct-acting antivirals for HCV. AIDS. 2021. https:\/\/doi.org\/10.1097\/QAD.0000000000002973.","journal-title":"AIDS"},{"key":"1730_CR11","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1097\/COH.0000000000000335","volume":"12","author":"I El Dika","year":"2017","unstructured":"El Dika I, Harding JJ, Abou-Alfa GK. Hepatocellular carcinoma in patients with HIV. Curr Opin HIV AIDS. 2017;12:20\u20135.","journal-title":"Curr Opin HIV AIDS"},{"key":"1730_CR12","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s00134-019-05524-1","volume":"45","author":"JM Miro","year":"2019","unstructured":"Miro JM, Grossi PA, Durand CM. Challenges in solid organ transplantation in people living with HIV. Intensive Care Med. 2019;45:398\u2013400.","journal-title":"Intensive Care Med"},{"key":"1730_CR13","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1056\/NEJMc0900837","volume":"362","author":"E Muller","year":"2010","unstructured":"Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362:2336\u20137.","journal-title":"N Engl J Med"},{"key":"1730_CR14","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1111\/ajt.16205","volume":"21","author":"CM Durand","year":"2021","unstructured":"Durand CM, Zhang W, Brown DM, Yu S, Desai N, Redd AD, et al. A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action. Am J Transplant. 2021;21:1754\u201364.","journal-title":"Am J Transplant"},{"key":"1730_CR15","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1056\/NEJMc1903013","volume":"381","author":"P Selhorst","year":"2019","unstructured":"Selhorst P, Combrinck CE, Manning K, Botha FCJ, Labuschagne JPL, Anthony C, et al. Longer-term outcomes of HIV-positive-to-HIV-positive renal transplantation. N Engl J Med. 2019;381:1387\u20139.","journal-title":"N Engl J Med"},{"key":"1730_CR16","doi-asserted-by":"publisher","first-page":"e23063","DOI":"10.1097\/MD.0000000000023063","volume":"99","author":"H Stadtler","year":"2020","unstructured":"Stadtler H, Wescott E, Hughes K, Chang J, Gao F, Klotman M, et al. HIV-1 diversity and compartmentalization in urine, semen, and blood. Medicine. 2020;99:e23063.","journal-title":"Medicine"},{"key":"1730_CR17","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1097\/QAD.0000000000002753","volume":"35","author":"K Hughes","year":"2021","unstructured":"Hughes K, Chang J, Stadtler H, Wyatt C, Klotman M, Blasi M. HIV-1 infection of the kidney: mechanisms and implications. AIDS. 2021;35:359\u201367.","journal-title":"AIDS"},{"key":"1730_CR18","doi-asserted-by":"publisher","first-page":"4728","DOI":"10.3748\/wjg.v24.i42.4728","volume":"24","author":"M Ganesan","year":"2018","unstructured":"Ganesan M, Poluektova LY, Kharbanda KK, Osna NA. Liver as a target of human immunodeficiency virus infection. World J Gastroenterol. 2018;24:4728\u201337.","journal-title":"World J Gastroenterol"},{"key":"1730_CR19","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1097\/QAD.0b013e328343489e","volume":"25","author":"I Abbate","year":"2011","unstructured":"Abbate I, Vlassi C, Rozera G, Bruselles A, Bartolini B, Giombini E, et al. Detection of quasispecies variants predicted to use CXCR4 by ultra-deep pyrosequencing during early HIV infection. AIDS. 2011;25:611\u20137.","journal-title":"AIDS"},{"key":"1730_CR20","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3390\/v13020176","volume":"13","author":"L Fabeni","year":"2021","unstructured":"Fabeni L, Rozera G, Berno G, Giombini E, Gori C, Orchi N, et al. Molecular transmission dynamics of primary HIV infections in Lazio Region, years 2013\u20132020. Viruses. 2021;13:176.","journal-title":"Viruses"},{"key":"1730_CR21","doi-asserted-by":"publisher","first-page":"e0187095","DOI":"10.1371\/journal.pone.0187095","volume":"12","author":"G Rozera","year":"2017","unstructured":"Rozera G, Fabbri G, Lorenzini P, Mastrorosa I, Timelli L, Zaccarelli M, et al. Peripheral blood HIV-1 DNA dynamics in antiretroviral-treated HIV\/HCV co-infected patients receiving directly-acting antivirals. PLoS ONE. 2017;12:e0187095.","journal-title":"PLoS ONE"},{"key":"1730_CR22","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1128\/JCM.00893-15","volume":"53","author":"L Fabeni","year":"2015","unstructured":"Fabeni L, Berno G, Svicher V, Ceccherini-Silberstein F, Gori C, Bertoli A, et al. Genotypic tropism testing in HIV-1 proviral DNA can provide useful information at low-level viremia. J Clin Microbiol. 2015;53:2935\u201341.","journal-title":"J Clin Microbiol"},{"key":"1730_CR23","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1093\/cid\/ciu020","volume":"58","author":"MM Santoro","year":"2014","unstructured":"Santoro MM, Fabeni L, Armenia D, Alteri C, Di Pinto D, Forbici F, et al. Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels. Clin Infect Dis. 2014;58:1156\u201364.","journal-title":"Clin Infect Dis"},{"key":"1730_CR24","first-page":"e53840","volume":"109","author":"E Serrao","year":"2016","unstructured":"Serrao E, Cherepanov P, Engelman AN. Amplification, next-generation sequencing, and genomic DNA mapping of retroviral integration sites. J Vis Exp. 2016;109:e53840.","journal-title":"J Vis Exp"},{"key":"1730_CR25","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1093\/bioinformatics\/btt768","volume":"30","author":"J Gregori","year":"2014","unstructured":"Gregori J, Salicr\u00fa M, Domingo E, Sanchez A, Esteban JI, Rodr\u00edguez-Fr\u00edas F, et al. Inference with viral quasispecies diversity indices: clonal and NGS approaches. Bioinformatics. 2014;30:1104\u201311.","journal-title":"Bioinformatics"},{"key":"1730_CR26","doi-asserted-by":"publisher","first-page":"e611","DOI":"10.1016\/S2352-3018(20)30200-9","volume":"7","author":"TS Bonny","year":"2020","unstructured":"Bonny TS, Kirby C, Martens C, Rose R, Desai N, Seisa M, et al. Outcomes of donor-derived superinfection screening in HIV-positive to HIV-positive kidney and liver transplantation: a multicentre, prospective, observational study. Lancet HIV. 2020;7:e611\u20139.","journal-title":"Lancet HIV"},{"key":"1730_CR27","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1056\/NEJMc1603850","volume":"375","author":"E Hathorn","year":"2016","unstructured":"Hathorn E, Smit E, Elsharkawy AM, Elsharkawy AM, Bramhall SR, Bufton SA, Allan S, et al. HIV-positive-to-HIV-positive liver transplantation. N Engl J Med. 2016;375:1807\u20139.","journal-title":"N Engl J Med"},{"key":"1730_CR28","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1056\/NEJMc1910189","volume":"382","author":"M Blasi","year":"2020","unstructured":"Blasi M, Stadtler H, Chang J, Hemmersbach-Miller M, Wyatt C, Klotman P, et al. Detection of donor\u2019s HIV strain in HIV-positive kidney-transplant recipient. N Engl J Med. 2020;382:195\u20137.","journal-title":"N Engl J Med"},{"key":"1730_CR29","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/S0140-6736(04)15596-7","volume":"363","author":"GS Gottlieb","year":"2004","unstructured":"Gottlieb GS, Nickle DC, Jensen MA, Wong KG, Grobler J, Li F, et al. Dual HIV-1 infection associated with rapid disease progression. Lancet. 2004;363:619\u201322.","journal-title":"Lancet"},{"key":"1730_CR30","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1093\/cid\/cir849","volume":"54","author":"M Cornelissen","year":"2012","unstructured":"Cornelissen M, Pasternak AO, Grijsen ML, Zorgdrager F, Bakker M, Blom P, et al. HIV-1 dual infection is associated with faster CD4R T-cell decline in a cohort of men with primary HIV infection. Clin Infect Dis. 2012;54:539\u201347.","journal-title":"Clin Infect Dis"},{"key":"1730_CR31","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/S1473-3099(13)70066-5","volume":"13","author":"AD Redd","year":"2013","unstructured":"Redd AD, Quinn TC, Tobian AAR. Frequency and implications of HIV superinfection. Lancet Infect Dis. 2013;13:622\u20138.","journal-title":"Lancet Infect Dis"},{"key":"1730_CR32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s11904-016-0297-9","volume":"13","author":"ML Freeman","year":"2016","unstructured":"Freeman ML, Lederman MM, Gianella S. Partners in crime: the role of CMV in immune dysregulation and clinical outcome during HIV infection. Curr HIV\/AIDS Rep. 2016;13:10\u20139.","journal-title":"Curr HIV\/AIDS Rep"},{"key":"1730_CR33","doi-asserted-by":"publisher","first-page":"S67","DOI":"10.1093\/infdis\/jiw217","volume":"214","author":"S Gianella","year":"2016","unstructured":"Gianella S, Letendre S. Cytomegalovirus and HIV: a dangerous Pas de Deux. J Infect Dis. 2016;214:S67\u201374.","journal-title":"J Infect Dis"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-021-01730-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-021-01730-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-021-01730-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T13:20:13Z","timestamp":1641475213000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-021-01730-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,6]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1730"],"URL":"https:\/\/doi.org\/10.1186\/s12985-021-01730-w","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,6]]},"assertion":[{"value":"3 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Both recipients signed a written consent for the use of their clinical samples for research activities. Authorization for use of clinical data and leftover biological samples for research is not needed by our Institute, according to the Italian Personal Data Protection Code (Legislative Decree No. 196 of 30 June 2003) as amended by Legislative Decree No. 101 of 10 August 2018, article 110-bis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}