{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:40:59Z","timestamp":1791852059166,"version":"4.3.4"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Highly active antiretroviral therapy (HAART) has reduced the incidence of VL\/HIV dramatically. However, HAART only partially prevents relapses, with one-year relapse rates ranging from 30 to 60%. Consequently, secondary prophylaxis is recommended for patients with &lt;200 CD4+ cells\/\u03bcL. In clinical practice, characterizing cellular immune response could help estimate the risk of relapse in VL\/HIV coinfected patients. In this study, the lymphoproliferative response after stimulation with soluble Leishmania antigen was assessed in 2022 and 2023 in three cases of VL\/HIV coinfection with long-term follow-up (17, 8 and 19 years). PCR and rK-39 results for Leishmania, HIV viral load, CD4 cell count, proliferation index, IFN-\u03b3, IL-2, IP-10, IL-10 and TNF-\u03b1 were determined. Heterogeneous results were obtained, with only one patient having developed specific cellular immunity against Leishmania. No cases of relapse were observed. The heterogeneity of lymphoproliferative test results in the three cases described highlights the need to identify surrogate markers of cure to guide maintenance or withdrawal of prophylaxis.<\/jats:p>","DOI":"10.3390\/microorganisms13030686","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T10:38:48Z","timestamp":1742380728000},"page":"686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Long-Term Follow-Up of Visceral Leishmaniasis and HIV Coinfected Patients Without Relapse: Lymphoproliferative Response After Stimulation with Soluble Leishmania Antigen"],"prefix":"10.3390","volume":"13","author":[{"given":"Bego\u00f1a","family":"Monge-Maillo","sequence":"first","affiliation":[{"name":"National Reference Unit for Tropical Diseases, Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, WHO Collaborating Center for Clinical Management of Leishmaniasis, Ram\u00f3n y Cajal Research Institute (IRYCIS), 28034 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Roger-Zapata","sequence":"additional","affiliation":[{"name":"Hospital Universitario del Sureste, 28500 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-5816","authenticated-orcid":false,"given":"Fernando","family":"Dronda","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, IRICYS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-7915","authenticated-orcid":false,"given":"Eugenia","family":"Carrillo","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Unidad de Leishmaniasis y Enfermedad de Chagas, WHO Collaborating Center for Leishmaniasis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-4659","authenticated-orcid":false,"given":"Javier","family":"Moreno","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Unidad de Leishmaniasis y Enfermedad de Chagas, WHO Collaborating Center for Leishmaniasis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1674-6304","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Corbacho-Loarte","sequence":"additional","affiliation":[{"name":"National Reference Unit for Tropical Diseases, Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, WHO Collaborating Center for Clinical Management of Leishmaniasis, Ram\u00f3n y Cajal Research Institute (IRYCIS), 28034 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Gayoso Cantero","sequence":"additional","affiliation":[{"name":"National Reference Unit for Tropical Diseases, Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, WHO Collaborating Center for Clinical Management of Leishmaniasis, Ram\u00f3n y Cajal Research Institute (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oihane","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Microbiology Department, Ram\u00f3n y Cajal University Hospital, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-1630","authenticated-orcid":false,"given":"Sandra","family":"Chamorro-Tojeiro","sequence":"additional","affiliation":[{"name":"National Reference Unit for Tropical Diseases, Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, WHO Collaborating Center for Clinical Management of Leishmaniasis, Ram\u00f3n y Cajal Research Institute (IRYCIS), 28034 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8735-4124","authenticated-orcid":false,"given":"Jose A.","family":"Perez-Molina","sequence":"additional","affiliation":[{"name":"National Reference Unit for Tropical Diseases, Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, WHO Collaborating Center for Clinical Management of Leishmaniasis, Ram\u00f3n y Cajal Research Institute (IRYCIS), 28034 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0336-7767","authenticated-orcid":false,"given":"Francesca","family":"Norman","sequence":"additional","affiliation":[{"name":"National Reference Unit for Tropical Diseases, Department of Infectious Diseases, Ram\u00f3n y Cajal University Hospital, WHO Collaborating Center for Clinical Management of 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(2014). Leishmania-HIV Co-infection: Clinical Presentation and Outcomes in an Urban Area in Brazil. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002816"},{"key":"ref_2","unstructured":"Ruiz-Postigo, J.A., Jain, S., Madjou, S., Maia-Elkhoury, A.N., Valadas, S., Warusavithana, S., Osman, M., Yajima, A., Lin, Z., and Beshah, A. (2025, January 15). Global Leishmaniasis Surveillance, 2022: Assessing Trends Over the Past 10 Years. Available online: https:\/\/www.who.int\/publications\/i\/item\/who-wer9840-471-487."},{"key":"ref_3","unstructured":"(2025, January 15). WHO Leishmaniasis. Available online: https:\/\/www.who.int\/health-topics\/leishmaniasis#tab=tab_1."},{"key":"ref_4","unstructured":"(2025, January 20). Joint United Nations Programme on HIV\/AIDS. UNAIDS Global AIDS Update 2023. Available online: https:\/\/thepath.unaids.org\/wp-content\/themes\/unaids2023\/assets\/files\/2023_report.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10096-022-04530-4","article-title":"Prevalence of visceral leishmaniasis among people with HIV: A systematic review and meta-analysis","volume":"42","author":"Kantzanou","year":"2023","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Monge-Maillo, B., Norman, F.F., Cruz, I., Alvar, J., and L\u00f3pez-V\u00e9lez, R. (2014). Visceral Leishmaniasis and HIV Coinfection in the Mediterranean Region. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003021"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1007\/s100960000364","article-title":"Prospective Evaluation and Follow-Up of European Patients with Visceral Leishmaniasis and HIV-1 Coinfection in the Era of Highly Active Antiretroviral Therapy","volume":"19","author":"Villanueva","year":"2000","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1086\/587899","article-title":"Concordant HIV Infection and Visceral Leishmaniasis in Ethiopia: The Influence of Antiretroviral Treatment and Other Factors on Outcome","volume":"46","author":"Collin","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/icb.1993.64","article-title":"Interferon-gamma and interleukin-4 in human Leishmania donovani infections","volume":"71","author":"Kemp","year":"1993","journal-title":"Immunol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Carrillo, E., Carrasco-Ant\u00f3n, N., L\u00f3pez-Medrano, F., Salto, E., Fern\u00e1ndez, L., San Mart\u00edn, J.V., Alvar, J., Aguado, J.M., and Moreno, J. (2015). Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004179"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.imbio.2014.01.005","article-title":"Whole blood assay and visceral leishmaniasis: Challenges and promises","volume":"219","author":"Singh","year":"2014","journal-title":"Immunobiology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kumar, R., Singh, N., Gautam, S., Singh, O.P., Gidwani, K., Rai, M., Sacks, D., Sundar, S., and Nyl\u00e9n, S. (2014). Leishmania Specific CD4 T Cells Release IFN\u03b3 That Limits Parasite Replication in Patients with Visceral Leishmaniasis. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003198"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Botana, L., Mat\u00eda, B., San Martin, J.V., Romero-Mat\u00e9, A., Castro, A., Molina, L., Fernandez, L., Ibarra-Meneses, A., Aguado, M., and S\u00e1nchez, C. (2018). Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00381"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ibarra-Meneses, A.V., Ghosh, P., Hossain, F., Chowdhury, R., Mondal, D., Alvar, J., Moreno, J., and Carrillo, E. (2017). IFN-\u03b3, IL-2, IP-10, and MIG as Biomarkers of Exposure to Leishmania spp., and of Cure in Human Visceral Leishmaniasis. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00200"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.actatropica.2016.09.026","article-title":"Lymphoproliferative response after stimulation with soluble leishmania antigen (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients","volume":"164","author":"Castro","year":"2016","journal-title":"Acta Tropica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/COH.0b013e32835211e9","article-title":"Mechanisms of interaction between protozoan parasites and HIV","volume":"7","author":"Andreani","year":"2012","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1046\/j.1365-3024.1999.00266.x","article-title":"Adversarial relationship between the Leishmania lipophosphoglycan and protein kinase C of host macrophages","volume":"21","author":"Turco","year":"1999","journal-title":"Parasite Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/1469-0691.12556","article-title":"Leishmaniasis in immunosuppressed individuals","volume":"20","author":"Carrillo","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1128\/IAI.67.10.5258-5264.1999","article-title":"Role of Leishmania donovani and Its Lipophosphoglycan in CD4+ T-cell Activation-Induced Human Immunodeficiency Virus Replication","volume":"67","author":"Wolday","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S1286-4579(03)00071-6","article-title":"Early mechanisms of Leishmania infection in human blood","volume":"5","author":"Moreno","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/sj.icb7100011","article-title":"Balancing immunity and pathology in visceral leishmaniasis","volume":"85","author":"Stanley","year":"2007","journal-title":"Immunol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1172\/JCI114009","article-title":"Requirement for T cells and effect of lymphokines in successful chemotherapy for an intracellular infection. Experimental visceral leishmaniasis","volume":"83","author":"Murray","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S0035-9203(00)90345-6","article-title":"HIV-Leishmania infantun co-infection: Humoral and cellular immune responses to the parasite after chemotherapy","volume":"94","author":"Moreno","year":"2000","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s100960100457","article-title":"Relapsing Visceral Leishmaniasis in HIV-Infected Patients Undergoing Successful Protease Inhibitor Therapy","volume":"20","author":"Casado","year":"2001","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cota, G.F., De Sousa, M.R., and Rabello, A. (2011). Predictors of Visceral Leishmaniasis Relapse in HIV-Infected Patients: A Systematic Review. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001153"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Samant, M., Sahu, U., Pandey, S.C., and Khare, P. (2021). Role of Cytokines in Experimental and Human Visceral Leishmaniasis. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.624009"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1006\/cyto.2000.0694","article-title":"IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis","volume":"12","author":"Bacellar","year":"2000","journal-title":"Cytokine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.clim.2005.06.015","article-title":"T cell subset and cytokine profiles in human visceral leishmaniasis during active and asymptomatic or sub-clinical infection with Leishmania donovani","volume":"117","author":"Hailu","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Botana, L., Ibarra-Meneses, A.V., Sanchez, C., Matia, B., San Martin, J.V., Moreno, J., and Carrillo, E. (2021). Leishmaniasis: A new method for confirming cure and detecting asymptomatic infection in patients receiving immunosuppressive treatment for autoimmune disease. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009662"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1473-3099(12)70348-1","article-title":"HIV-1 protease inhibitors for treatment of visceral leishmaniasis in HIV-co-infected individuals","volume":"13","author":"Diro","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10096-014-2229-1","article-title":"High levels of CD4+ CTLA-4+ Treg cells and CCR5 density in HIV-1-infected patients with visceral leishmaniasis","volume":"34","author":"Vallejo","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Adriaensen, W., Dorlo, T.P.C., Vanham, G., Kestens, L., Kaye, P.M., and Van Griensven, J. (2018). Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01943"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/3\/686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:42Z","timestamp":1760029002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/3\/686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["microorganisms13030686"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13030686","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]}}}