{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:20:09Z","timestamp":1788448809293,"version":"build-2803163510"},"posted":{"date-parts":[[2023,3,6]]},"group-title":"HIV\/AIDS","reference-count":38,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    is an opportunistic parasitic infection. An immunocompromised state increases the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL), which has a \u223c5% fatality rate even with treatment. HIV coinfection increases the risk of death from VL.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of\n                    <jats:italic>L. infantum<\/jats:italic>\n                    infection in HIV positive subjects residing in the state of Rio Grande do Norte, Brazil (n=1,372) and of these a subgroup of subjects were followed longitudinally. Subsequent incident cases of VL were ascertained from a public health database through 2018. A subgroup (n=69) of the cross-sectional study subjects was chosen to assess immune status (T cell activation, senescence, exhaustion) and outcome. The data were compared between asymptomatic HIV+\/\n                    <jats:italic>L. infantum+<\/jats:italic>\n                    (HIV\/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response \u2013 Leishmanin skin test), AIDS\/VL, HIV+ only (HIV+), and Non-HIV\/Non\n                    <jats:italic>L. infantum<\/jats:italic>\n                    infection (control subjects).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgG\n                    <jats:italic>Leishmania<\/jats:italic>\n                    antibodies. After 3 years, 2.4% (8 of 333) of these HIV\/Leish coinfected subjects developed AIDS\/VL, whereas 1.05% (11 of 1,039) of HIV subjects with negative leishmania serology developed AIDS\/VL. Poor adherence to antiretroviral therapy (p=0.0008) or prior opportunistic infections (p=0.0007) was associated with development of AIDS\/VL. CD4+ (p=0.29) and CD8+ (p=0.38) T cells counts or viral load (p=0.34) were similar between asymptomatic HIV\/Leish and HIV subjects. However, activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>+<\/jats:sup>\n                    HLA-DR\n                    <jats:sup>+<\/jats:sup>\n                    T cells were higher in asymptomatic HIV\/Leish than HIV group. Likewise, senescent (CD57\n                    <jats:sup>+<\/jats:sup>\n                    ) or exhausted (PD1\n                    <jats:sup>+<\/jats:sup>\n                    ) CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were higher in asymptomatic HIV\/Leish than in AIDS\/VL or HIV groups.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    Although asymptomatic HIV\/Leish subjects had normal and similar CD4+ and CD8+ T cells counts, their CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells had increased activation, senescence, and exhaustion, which could contribute to risk of developing VL.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Author Summary<\/jats:title>\n                  <jats:p>\n                    The frequency of asymptomatic HIV\/Leish\n                    <jats:italic>mania infantum<\/jats:italic>\n                    (HIV\/Leish) infection and the immunological status of subjects with HIV+ residing in the state of Rio Grande do Norte, Brazil, between 2014 and 2016 were studied. A high frequency of asymptomatic HIV\/Leish\n                    <jats:italic>mania infantum<\/jats:italic>\n                    infection (HIV subjects with positive anti-IgG Leishmania antibodies) was found. Asymptomatic HIV\/Leish subjects had CD8 T cells with higher markers of activation, senescence and exhaustion than the other groups (HIV-alone, symptomatic VL, Recovered VL, DTH+, AIDS\/VL and Controls subjects). Poor adherence to antiretroviral therapy or history of previous opportunistic infection was associated with AIDS\/VL. Asymptomatic HIV\/Leish had high relative risk of developing AIDS\/VL. Thus, subjects with HIV residing in endemic areas for VL should be assessed for their\n                    <jats:italic>L. infantum<\/jats:italic>\n                    infection status and advised to closely adhere to ART.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.03.06.23286828","type":"posted-content","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T22:20:18Z","timestamp":1678314018000},"source":"Crossref","is-referenced-by-count":3,"title":["T-cell activation, senescence, and exhaustion in asymptomatic HIV\/Leish\n                  <i>mania infantum<\/i>\n                  co-infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-8376","authenticated-orcid":false,"given":"Carolina","family":"de Oliveira Mendes-Aguiar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoella","family":"do Monte 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