{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:16:38Z","timestamp":1792790198057,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"EDCTP2 programme","doi-asserted-by":"publisher","award":["TMA2018SF-2446"],"award-info":[{"award-number":["TMA2018SF-2446"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NRF","award":["TMA2018SF-2446"],"award-info":[{"award-number":["TMA2018SF-2446"]}]},{"name":"MRC","award":["TMA2018SF-2446"],"award-info":[{"award-number":["TMA2018SF-2446"]}]},{"name":"PRF","award":["TMA2018SF-2446"],"award-info":[{"award-number":["TMA2018SF-2446"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Kaposi\u2019s sarcoma (KS) is an AIDS-defining illness caused by Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients (n = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa. Demographic and clinical data, KS staging and response to treatment were extracted from patient files, while long-term survival was ascertained from hospital records. KSHV serology and VL and hIL-6 were determined empirically from patients\u2019 blood. All patients were HIV-positive adults, the majority of whom were on HAART at the time of recruitment. KSHV VL was detectable in 65 patients\u2019 blood (median: 280.5\/106 cells (IQR: 69.7\u20131727.3)) and was highest in patients with S1 HIV-related systemic disease (median 1066.9\/106 cells, IQR: 70.5\u201311,269.6). KSHV VL was associated with the S1 stage in a binomial regression controlling for confounders (adjusted odds ratio 5.55, 95% CI: 1.28\u201324.14, p = 0.022). A subset of six patients identified to have extremely high KSHV VLs was predominantly T1 stage with pulmonary KS, and most had died at follow-up. In our cohort, elevated KSHV VL is associated with systemic HIV-related illness in KS disease. Extremely high KSHV VLs warrant further investigation for patients potentially requiring intensive treatment and investigation for progression or diagnosis of concurrent KSHV lytic syndromes.<\/jats:p>","DOI":"10.3390\/v16020189","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T08:56:01Z","timestamp":1706259361000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Significance of Elevated KSHV Viral Load in HIV-Related Kaposi\u2019s Sarcoma Patients in South Africa"],"prefix":"10.3390","volume":"16","author":[{"given":"Rebecca Monica","family":"Tibenderana","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1865-0795","authenticated-orcid":false,"given":"Melissa Jayne","family":"Blumenthal","sequence":"additional","affiliation":[{"name":"Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa"},{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Bukajumbe","sequence":"additional","affiliation":[{"name":"Aberdeen Surgery, Aberdeen, NSW 2336, Australia"},{"name":"Hatchile Consult Ltd., Kampala 759125, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-3828","authenticated-orcid":false,"given":"Georgia","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa"},{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-4231","authenticated-orcid":false,"given":"Zainab","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/infdis\/jix569","article-title":"Kaposi Sarcoma-Associated Herpesvirus in a Rural Ugandan Cohort, 1992\u20132008","volume":"217","author":"Newton","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/infdis\/148.2.339","article-title":"Acquired Immune Deficiency Syndrome in the United States: The First 1000 Cases","volume":"148","author":"Jaffe","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1097\/01.qai.0000132495.89162.c0","article-title":"Water, Socioeconomic Factors, and Human Herpesvirus 8 Infection in Ugandan Children and Their Mothers","volume":"38","author":"Mbulaiteye","year":"2005","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/01913120802343871","article-title":"Ultrastructure of Kaposi Sarcoma","volume":"32","author":"Orenstein","year":"2008","journal-title":"Ultrastruct. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/path.4441","article-title":"The Role of Kaposi Sarcoma-Associated Herpesvirus in the Pathogenesis of Kaposi Sarcoma","volume":"235","author":"Gramolelli","year":"2015","journal-title":"J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S1473-3099(02)00263-3","article-title":"Update on Kaposi\u2019s Sarcoma and Other HHV8 Associated Diseases. Part 1: Epidemiology, Environmental Predispositions, Clinical Manifestations, and Therapy","volume":"2","author":"Hengge","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","first-page":"2012","article-title":"Gastrointestinal Kaposi\u2019s Sarcoma","volume":"107","author":"Lee","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Polizzotto, M.N., Uldrick, T.S., Hu, D., and Yarchoan, R. (2012). Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00073"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1093\/cid\/civ996","article-title":"Clinical Features and Outcomes of Patients with Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-Associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS)","volume":"62","author":"Polizzotto","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1086\/654798","article-title":"An Interleukin-6-Related Systemic Inflammatory Syndrome in Patients Co-Infected with Kaposi Sarcoma-Associated Herpesvirus and HIV but without Multicentric Castleman Disease","volume":"51","author":"Uldrick","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1182\/blood-2019-01-893339","article-title":"Viral, Immunologic, and Clinical Features of Primary Effusion Lymphoma","volume":"133","author":"Lurain","year":"2019","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00002030-199601000-00009","article-title":"Multicentric Castleman\u2019s Disease in HIV Infection: A Clinical and Pathological Study of 20 Patients","volume":"10","author":"Oksenhendler","year":"1996","journal-title":"AIDS"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1097\/QAD.0000000000001567","article-title":"HIV-Associated Kaposi Sarcoma and Related Diseases","volume":"31","author":"Goncalves","year":"2017","journal-title":"AIDS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0140-6736(07)61050-2","article-title":"Incidence of Cancers in People with HIV\/AIDS Compared with Immunosuppressed Transplant Recipients: A Meta-Analysis","volume":"370","author":"Grulich","year":"2007","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.6004\/jnccn.2019.0008","article-title":"AIDS-Related Kaposi Sarcoma, Version 2.2019","volume":"17","author":"Reid","year":"2019","journal-title":"JNCCN J. Natl. Compr. Cancer Netw."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1200\/JCO.1989.7.9.1201","article-title":"Kaposi\u2019s Sarcoma in the Acquired Immune Deficiency Syndrome: A Proposal for Uniform Evaluation, Response, and Staging Criteria","volume":"7","author":"Krown","year":"1989","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1200\/JCO.1997.15.9.3085","article-title":"AIDS-Related Kaposi\u2019s Sarcoma: Prospective Validation of the AIDS Clinical Trials Group Staging Classification. AIDS Clinical Trials Group Oncology Committee","volume":"15","author":"Krown","year":"1997","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1097\/QAI.0000000000001286","article-title":"Evaluation of a Predictive Staging Model for HIV-Associated Kaposi Sarcoma in Uganda","volume":"74","author":"Okuku","year":"2017","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1200\/JCO.2003.10.162","article-title":"AIDS-Related Kaposi\u2019s Sarcoma: Evaluation of Potential New Prognostic Factors and Assessment of the AIDS Clinical Trial Group Staging System in the Haart Era\u2014The Italian Cooperative Group on AIDS and Tumors and the Italian Cohort of Patients Na\u00efve from Antiretrovirals","volume":"21","author":"Nasti","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1097\/QAD.0b013e3282fc9c03","article-title":"Predicting the Evolution of Kaposi Sarcoma, in the Highly Active Antiretroviral Therapy Era","volume":"22","author":"Boffi","year":"2008","journal-title":"AIDS"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1056\/NEJMc070508","article-title":"HIV-Associated Kaposi\u2019s Sarcoma with a High CD4 Count and a Low Viral Load","volume":"357","author":"Maurer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S0140-6736(19)33222-2","article-title":"Treatment of Advanced AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A Three-Arm, Open-Label, Randomised, Non-Inferiority Trial","volume":"395","author":"Krown","year":"2020","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Freeman, E.E., Busakhala, N., Regan, S., Asirwa, F.C., Wenger, M., Seth, D., Moon, K.C., Semeere, A., Maurer, T., and Wools-Kaloustian, K. (2020). Real-World Use of Chemotherapy for Kaposi\u2019s Sarcoma in a Large Community-Based HIV Primary Care System in Kenya. BMC Cancer, 20.","DOI":"10.1186\/s12885-019-6506-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S0140-6736(95)91619-9","article-title":"Detection of Kaposi Sarcoma Associated Herpesvirus in Peripheral Blood of HIV-Infected Individuals and Progression to Kaposi\u2019s Sarcoma","volume":"346","author":"Whitby","year":"1995","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00569-18","DOI":"10.1128\/JCM.00569-18","article-title":"Usefulness of Kaposi\u2019s Sarcoma-Associated Herpesvirus (KSHV) DNA Viral Load in Whole Blood for Diagnosis and Monitoring of KSHV-Associated Diseases","volume":"56","author":"Jary","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1086\/521625","article-title":"Relationship between the Quantity of Kaposi Sarcoma\u2013Associated Herpesvirus (KSHV) in Peripheral Blood and Effusion Fluid Samples and KSHV\u2014Associated Disease","volume":"196","author":"Marcelin","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jcv.2016.02.019","article-title":"HHV-8 DNA Replication Correlates with the Clinical Status in AIDS-Related Kaposi\u2019s Sarcoma","volume":"78","author":"Broccolo","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1097\/QAD.0b013e3282202b7d","article-title":"Human Herpesvirus 8 Presence and Viral Load Are Associated with the Progression of AIDS-Associated Kaposi\u2019s Sarcoma","volume":"21","author":"Laney","year":"2007","journal-title":"AIDS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1128\/JCM.39.12.4269-4273.2001","article-title":"Viral Load of Human Herpesvirus 8 in Peripheral Blood of Human Immunodeficiency Virus-Infected Patients with Kaposi\u2019s Sarcoma","volume":"39","author":"Tedeschi","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6977","DOI":"10.1182\/blood-2010-11-317610","article-title":"High-Dose Zidovudine plus Valganciclovir for Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease: A Pilot Study of Virus-Activated Cytotoxic Therapy","volume":"117","author":"Uldrick","year":"2011","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1182\/blood-2003-03-0951","article-title":"Rituximab Therapy for HIV-Associated Castleman Disease","volume":"102","author":"Marcelin","year":"2003","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/infdis\/jiz180","article-title":"The Contribution of Kaposi\u2019s Sarcoma-Associated Herpesvirus to Mortality in Hospitalized Human Immunodeficiency Virus-Infected Patients Being Investigated for Tuberculosis in South Africa","volume":"220","author":"Blumenthal","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Blumenthal, M.J., Lambarey, H., Chetram, A., Riou, C., Wilkinson, R.J., and Sch\u00e4fer, G. (2022). Kaposi\u2019s Sarcoma-Associated Herpesvirus, but Not Epstein-Barr Virus, Co-Infection Associates with Coronavirus Disease 2019 Severity and Outcome in South African Patients. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.795555"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1086\/654800","article-title":"Evaluation of Plasma Human Herpesvirus 8 DNA as a Marker of Clinical Outcomes during Antiretroviral Therapy for AIDS-Related Kaposi Sarcoma in Zimbabwe","volume":"51","author":"Borok","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.canep.2018.08.005","article-title":"EPHA2 Sequence Variants Are Associated with Susceptibility to Kaposi\u2019s Sarcoma-Associated Herpesvirus Infection and Kaposi\u2019s Sarcoma Prevalence in HIV-Infected Patients","volume":"56","author":"Blumenthal","year":"2018","journal-title":"Cancer Epidemiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mwafongo, A.A., Rosenberg, N.E., Ng\u2019ambi, W., Werner, A.B., Garneau, W.M., Gumulira, J., Phiri, S., and Hosseinipour, M.C. (2014). Treatment Outcomes of AIDS-Associated Kaposi\u2019s Sarcoma under a Routine Antiretroviral Therapy Program in Lilongwe, Malawi: Bleomycin\/Vincristine Compared to Vincristine Monotherapy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091020"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1097\/QAI.0b013e3181f275fd","article-title":"Treatment Interruption in a Primary Care Antiretroviral Therapy Programme in South Africa: Cohort Analysis of Trends and Risk Factors","volume":"55","author":"Kranzer","year":"2010","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jim.2010.02.015","article-title":"Detection of Antibodies to Kaposi\u2019s Sarcoma-Associated Herpesvirus: A New Approach Using K8.1 ELISA and a Newly Developed Recombinant LANA ELISA","volume":"356","author":"Mbisa","year":"2010","journal-title":"J. Immunol. Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/ijc.10190","article-title":"Prevalence of Kaposi\u2019s Sarcoma-Associated Herpesvirus Infection in Sex Workers and Women from the General Population in Spain","volume":"98","author":"Marshall","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_41","unstructured":"Blumenthal, M., Schutz, C., Barr, D., Marshall, V., Locketz, M., Whitby, D., Katz, A., Uldrick, T., Meintjes, G., and Sch\u00e4fer, G. (2019, January 4\u20139). The Contribution of KSHV to Mortality in Hospitalized HIV-Infected Patients Being Investigated for Tuberculosis in South Africa. Proceedings of the Conference on Retroviruses and Opportunistic Infection, Seattle, WA, USA."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/ijc.22205","article-title":"Reactivation of Kaposi\u2019s Sarcoma-Associated Herpesvirus by Natural Products from Kaposi\u2019s Sarcoma Endemic Regions","volume":"120","author":"Whitby","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/infdis\/jiv123","article-title":"Factors Associated with Plasma IL-6 Levels during HIV Infection","volume":"212","author":"Borges","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/00401706.1962.10490038","article-title":"Transformation of the Independent Variables","volume":"4","author":"Box","year":"1962","journal-title":"Technometrics"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/2\/189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:49:51Z","timestamp":1760104191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/2\/189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,26]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["v16020189"],"URL":"https:\/\/doi.org\/10.3390\/v16020189","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,26]]}}}