T-cell activation, senescence, and exhaustion in asymptomatic HIV/Leishmania infantumco-infection
Authors: de Oliveira Mendes-Aguiar Carolina , do Monte Alves Manoella , Lopes Machado Amanda de Albuquerque , de Góis Monteiro Glória Regina , Medeiros Iara Marques , Queiroz Jose Wilton , Lima Iraci Duarte , Pearson Richard D. , Wilson Mary E. , Glesby Marshall J. , do Nascimento Eliana Lúcia Tomaz , Bezerra Jerônimo Selma Maria 
Published: March 2023

Background

Leishmania infantumis 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.

Methods

A cross-sectional study was performed between 2014 and 2016 to determine the prevalence ofL. infantuminfection 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+/L. infantum+(HIV/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response – Leishmanin skin test), AIDS/VL, HIV+ only (HIV+), and Non-HIV/NonL. infantuminfection (control subjects).

Results

The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgGLeishmaniaantibodies. 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.

Conclusion

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.

Author Summary

The frequency of asymptomatic HIV/Leishmania infantum(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/Leishmania infantuminfection (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 theirL. infantuminfection status and advised to closely adhere to ART.