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T-cell activation, senescence, and exhaustion in asymptomatic HIV/Leish mania infantum co-infection
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T-cell activation, senescence, and exhaustion in asymptomatic HIV/Leish mania infantum co-infection

Carolina de Oliveira Mendes-Aguiar, Manoella do Monte Alves, Amanda de Albuquerque Lopes Machado, Glória Regina de Góis Monteiro, Iara Marques Medeiros, Jose Wilton Queiroz, Iraci Duarte Lima, Richard D Pearson, Mary E Wilson, Marshall J Glesby, …
medRxiv : the preprint server for health sciences
03/06/2023
DOI: 10.1101/2023.03.06.23286828
PMCID: PMC10029033
PMID: 36945413
url
https://doi.org/10.1101/2023.03.06.23286828View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

is an opportunistic parasitic infection. An immunocompromised state increases the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL), which has a ∼5% fatality rate even with treatment. HIV coinfection increases the risk of death from VL. A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of 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+/ (HIV/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response - Leishmanin skin test), AIDS/VL, HIV+ only (HIV+), and Non-HIV/Non infection (control subjects). The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgG 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 CD38 HLA-DR T cells were higher in asymptomatic HIV/Leish than HIV group. Likewise, senescent (CD57 ) or exhausted (PD1 ) CD8 T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups. Although asymptomatic HIV/Leish subjects had normal and similar CD4+ and CD8+ T cells counts, their CD8 T cells had increased activation, senescence, and exhaustion, which could contribute to risk of developing VL. The frequency of asymptomatic HIV/Leish (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 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 infection status and advised to closely adhere to ART.

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