{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:15:59Z","timestamp":1790828159006,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K43TW011095"],"award-info":[{"award-number":["K43TW011095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K43TW011418"],"award-info":[{"award-number":["K43TW011418"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy, with the Kaposi sarcoma-associated herpes virus (KSHV) as its etiologic agent. Upon treatment with chemotherapy, a proportion of HIV-associated KS patients experience disease recurrence within a few months of completing treatment. We aimed at determining whether KSHV-specific adaptive immune responses were associated with KS recurrence upon complete remission. We conducted a prospective cohort study. The primary outcome was the recurrence of HIV-associated KS. An immunofluorescence assay was used to determine anti-KSHV antibodies, an enzyme-linked immunospot was conducted for T cell responses, PCR was carried out to determine KSHV status, and flow cytometry was used for CD4 counting and immunophenotyping. KSHV detection in PBMCs was high and not associated with KS recurrence-free survival (p = 0.29). Anti-KSHV antibody titers were high and not associated with recurrence-free survival (p = 0.63). KSHV-specific T cell responses dropped from baseline levels among individuals with recurrence, but the drop was not statistically significant. Individuals experiencing KS recurrence had a significantly higher proportion of T cell subsets expressing PD1, while those with sustained remission had a significant increase in CD4 T cell counts from baseline levels during the follow-up period (p = 0.02). Anti-KSHV antibodies are not a good correlate of protection from KS recurrence. T cells in individuals experiencing KS recurrence hadhigh PD1 expression, while an increase in CD4 counts was associated with sustained KS remission.<\/jats:p>","DOI":"10.3390\/tropicalmed9060134","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T03:42:06Z","timestamp":1718682126000},"page":"134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association between KSHV-Specific Humoral and T Cell Responses with Recurrence of HIV-Associated Kaposi Sarcoma"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2263-2572","authenticated-orcid":false,"given":"Marie-Claire","family":"Mukasine","sequence":"first","affiliation":[{"name":"Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka P.O. Box 50110, Zambia"},{"name":"HHV8 Research Molecular Virology Laboratory, University Teaching Hospital, Lusaka P.O. Box 50110, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Mulundu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka P.O. Box 50110, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musonda","family":"Kawimbe","sequence":"additional","affiliation":[{"name":"HHV8 Research Molecular Virology Laboratory, University Teaching Hospital, Lusaka P.O. Box 50110, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keagan","family":"Mutale","sequence":"additional","affiliation":[{"name":"HHV8 Research Molecular Virology Laboratory, University Teaching Hospital, Lusaka P.O. Box 50110, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chibamba","family":"Mumba","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka P.O. Box 50110, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0574-6595","authenticated-orcid":false,"given":"Salum J.","family":"Lidenge","sequence":"additional","affiliation":[{"name":"Ocean Road Cancer Institute, Dar es Salaam P.O. Box 3592, Tanzania"},{"name":"Department of Clinical Oncology, Muhimbili University of Health and Allied Sciences, Dar es Salaam P.O. Box 65001, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-4128","authenticated-orcid":false,"given":"Owen","family":"Ngalamika","sequence":"additional","affiliation":[{"name":"HHV8 Research Molecular Virology Laboratory, University Teaching Hospital, Lusaka P.O. Box 50110, Zambia"},{"name":"Dermatology and Venereology Division, University Teaching Hospital, University of Zambia School of Medicine, Lusaka P.O. Box 50110, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2174\/1570162X16666180711103610","article-title":"Therapeutic Outcomes in AIDS-Associated Kaposi\u2019s Sarcoma Patients on Antiretroviral Therapy Treated with Chemotherapy at Two Tertiary Hospitals in Lusaka, Zambia","volume":"16","author":"Mtonga","year":"2018","journal-title":"Curr. HIV Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1093\/cid\/ciz762","article-title":"Recurrence and Occurrence of Kaposi\u2019s Sarcoma in Patients Living With Human Immunodeficiency Virus (HIV) and on Antiretroviral Therapy, Despite Suppressed HIV Viremia","volume":"70","author":"Palich","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ngalamika, O., Mukasine, M.C., Kawimbe, M., and Vally, F. (2021). Viral and immunological markers of HIV-associated Kaposi sarcoma recurrence. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0254177"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lambarey, H., Blumenthal, M.J., Chetram, A., Joyimbana, W., Jennings, L., Orrell, C., and Schafer, G. (2024). Reactivation of Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) by SARS-CoV-2 in non-hospitalised HIV-infected patients. EBioMedicine, 100.","DOI":"10.1016\/j.ebiom.2024.104986"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1111\/j.1537-2995.2009.02559.x","article-title":"Human herpesvirus 8 genomes and seroprevalence in United States blood donors","volume":"50","author":"Qu","year":"2010","journal-title":"Transfusion"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102167","DOI":"10.1016\/j.canep.2022.102167","article-title":"Epidemiology of Kaposi\u2019s sarcoma in sub-Saharan Africa","volume":"78","author":"Motlhale","year":"2022","journal-title":"Cancer Epidemiol."},{"key":"ref_7","first-page":"e13384","article-title":"Iatrogenic Kaposi Sarcoma Precipitated by Anti-Tumor Necrosis Factor-Alpha (Anti-TNF-alpha) Therapy","volume":"13","author":"Mariappan","year":"2021","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/ijc.30129","article-title":"Is human herpesvirus 8 infection more common in men than in women? Systematic review and meta-analysis","volume":"139","author":"Begre","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kumar, P., Kuwa, N.Y., Minhas, V., Marimo, C., Shea, D.M., Kankasa, C., and Wood, C. (2013). Higher levels of neutralizing antibodies against KSHV in KS patients compared to asymptomatic individuals from Zambia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071254"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.diagmicrobio.2013.02.026","article-title":"Quantitative determinations of anti-Kaposi sarcoma-associated herpesvirus antibody levels in men who have sex with men","volume":"76","author":"Gogineni","year":"2013","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/sj.bjc.6601113","article-title":"Infection with Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) and human immunodeficiency virus (HIV) in relation to the risk and clinical presentation of Kaposi\u2019s sarcoma in Uganda","volume":"89","author":"Newton","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/ijc.10818","article-title":"Risk factors for Kaposi\u2019s sarcoma: A case-control study of HIV-seronegative people in Uganda","volume":"103","author":"Ziegler","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"340356","DOI":"10.1155\/2010\/340356","article-title":"The T-Cell Immune Response against Kaposi\u2019s Sarcoma-Associated Herpesvirus","volume":"2010","author":"Robey","year":"2010","journal-title":"Adv. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7323","DOI":"10.1038\/s41467-021-27623-8","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda","volume":"12","author":"Nalwoga","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Robey, R.C., Lagos, D., Gratrix, F., Henderson, S., Matthews, N.C., Vart, R.J., Bower, M., Boshoff, C., and Gotch, F.M. (2009). The CD8 and CD4 T-cell response against Kaposi\u2019s sarcoma-associated herpesvirus is skewed towards early and late lytic antigens. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005890"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1097\/QAD.0b013e3283300a91","article-title":"Cellular immune responses and disease control in acute AIDS-associated Kaposi\u2019s sarcoma","volume":"23","author":"Bihl","year":"2009","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1128\/CVI.00487-07","article-title":"Development of an immunofluorescence assay using recombinant proteins expressed in insect cells to screen and confirm presence of human herpesvirus 8-specific antibodies","volume":"15","author":"Minhas","year":"2008","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1086\/313947","article-title":"Clinical relevance of age-related immune dysfunction","volume":"31","author":"Castle","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1086\/589865","article-title":"Long-term prognosis of HIV-infected patients with Kaposi sarcoma treated with pegylated liposomal doxorubicin","volume":"47","author":"Palacios","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lidenge, S.J., Tso, F.Y., Mortazavi, Y., Ngowi, J.R., Shea, D.M., Mwaiselage, J., Wood, C., and West, J.T. (2020). Viral and Immunological Analytes are Poor Predictors of the Clinical Treatment Response in Kaposi\u2019s Sarcoma Patients. Cancers, 12.","DOI":"10.3390\/cancers12061594"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13027-017-0147-4","article-title":"Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma","volume":"12","author":"Starita","year":"2017","journal-title":"Infect. Agent. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/S0002-9440(10)65069-9","article-title":"Induction of HHV-8 lytic cycle replication by inflammatory cytokines produced by HIV-1-infected T cells","volume":"156","author":"Mercader","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"300060518764747","DOI":"10.1177\/0300060518764747","article-title":"Seroepidemiology and phylogenetic analysis of human herpesvirus type 8 in injection drug users and men who have sex with men in northern Taiwan","volume":"48","author":"Lee","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8102","DOI":"10.1016\/j.vaccine.2007.09.046","article-title":"Antibodies against Kaposi sarcoma-associated herpes virus (KSHV) complement control protein (KCP) in infected individuals","volume":"25","author":"Okroj","year":"2007","journal-title":"Vaccine"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-9378-3-10","article-title":"Human herpesvirus-8 (HHV-8) sero-detection and HIV association in Kaposi\u2019s sarcoma (KS), non-KS tumors and non-neoplastic conditions","volume":"3","author":"Mwakigonja","year":"2008","journal-title":"Infect. Agent. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e29324","DOI":"10.1002\/jmv.29324","article-title":"Evaluation of human herpesvirus-8 viremia and antibody positivity in patients with HIV infection with human herpesvirus-8-related diseases","volume":"95","author":"Watanabe","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Semango, G.P., Charles, R.M., Swai, C.I., Mremi, A., Amsi, P., Sonda, T., Shao, E.R., Mavura, D.R., Joosten, L.A.B., and Sauli, E. (2018). Prevalence and associated risk factors for Kaposi\u2019s sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: A retrospective hospital-based study. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5155-2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1177\/1545109709341852","article-title":"A retrospective analysis of AIDS-associated Kaposi\u2019s sarcoma in patients with undetectable HIV viral loads and CD4 counts greater than 300 cells\/mm3","volume":"8","author":"Mani","year":"2009","journal-title":"J. Int. Assoc. Physicians AIDS Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1200\/JCO.2005.04.156","article-title":"Profile of patients with Kaposi\u2019s sarcoma in the era of highly active antiretroviral therapy","volume":"23","author":"Gallafent","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.virol.2019.07.024","article-title":"Expression of PD-1 and PD-Ls in Kaposi\u2019s sarcoma and regulation by oncogenic herpesvirus lytic reactivation","volume":"536","author":"Chen","year":"2019","journal-title":"Virology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"72961","DOI":"10.18632\/oncotarget.12150","article-title":"PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma","volume":"7","author":"Lambert","year":"2016","journal-title":"Oncotarget"}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/9\/6\/134\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:00:15Z","timestamp":1760108415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/9\/6\/134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,18]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["tropicalmed9060134"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed9060134","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,18]]}}}