1. High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil
- Author
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Laise de Moraes, Luciane Amorim Santos, Liã Bárbara Arruda, Maria da Purificação Pereira da Silva, Márcio de Oliveira Silva, José Adriano Góes Silva, André Ramos, Marcos Bastos dos Santos, Felipe Guimarães Torres, Cibele Orge, Antonio Marcos dos Santos Teixeira, Thiago Santos Vieira, Laura Ramírez, Manuel Soto, Maria Fernanda Rios Grassi, Isadora Cristina de Siqueira, Dorcas Lamounier Costa, Carlos Henrique Nery Costa, Bruno de Bezerril Andrade, Kevan Akrami, Camila Indiani de Oliveira, Viviane Sampaio Boaventura, Manoel Barral-Netto, Aldina Barral, Anne-Mieke Vandamme, Johan Van Weyenbergh, and Ricardo Khouri
- Subjects
HIV-1 ,Leishmania infantum ,visceral leishmaniasis ,immune activation ,hostpathogen interaction ,Microbiology ,QR1-502 - Abstract
Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.
- Published
- 2023
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