Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients

Submitted by Sandra Infurna ([email protected]) on 2017-03-06T17:02:56Z No. of bitstreams: 1 marialuciana_freitas_etal_IOC_2016.pdf: 2176381 bytes, checksum: 0ab82bd56ce1c70b0455bf90afeb8834 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-03-06T17:20:12Z (GMT) No. of bitstreams: 1 marialuciana_freitas_etal_IOC_2016.pdf: 2176381 bytes, checksum: 0ab82bd56ce1c70b0455bf90afeb8834 (MD5)Made available in DSpace on 2017-03-06T17:20:12Z (GMT). No. of bitstreams: 1 marialuciana_freitas_etal_IOC_2016.pdf: 2176381 bytes, checksum: 0ab82bd56ce1c70b0455bf90afeb8834 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Pesquisas Clínicas e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil / Fundação Hospitalar do Estado de Minas Gerais. Hospital Eduardo de Menezes. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Pesquisas Clínicas e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil / Fundação Hospitalar do Estado de Minas Gerais. Hospital Eduardo de Menezes. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz, Instituto Oswaldo Cruz; Laboratório de AIDS e Imunologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Pesquisas Clínicas e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil / Instituto Federal de Educação, Ciência e Tecnologia. Núcleo de Ciências Biomédicas Aplicadas. Rio de Janeiro, RJ, Brasil.The maintenance of chronic immune activation due to leishmaniasis or even due to microbial translocation is associated with immunosenescence and may contribute to frequent relapses. Our aim was to investigate whether patients with HIV-associated visceral leishmaniasis (VL/HIV) who experience a single episode of VL have different immunological behaviors in comparison to those who experience frequent relapses. VL/HIV patients were allocated to non-relapsing (NR, n = 6) and relapsing (R, n = 11) groups and were followed from the active phase of VL up to 12 months post-treatment (mpt). The patients were receiving highly active antiretroviral therapy (HAART) and secondary prophylaxis after VL therapy. During active VL, the two groups were similar in all immunological parameters, including the parasite load. At 6 and 12 mpt, the NR group showed a significant gain of CD4+ T cells, a reduction of lymphocyte activation, and lower soluble CD14 and anti-Leishmania IgG3 levels compared to the R group. The viral load remained low, without correlation with the activation. The two groups showed elevated but similar percentages of senescent T cells. These findings suggest a decreased ability of the R group to downmodulate immune activation compared to the NR group. Such functional impairment of the effector response may be a useful indicator for predicting clinical prognosis and recommending starting or stopping secondary prophylaxis

Immune constitution of visceral leishmaniasis/HIV (VL/HIV)-co-infected patients. Absolute counts of CD4⁺ T lymphocytes during the prospective follow-up of co-infected patients (A) and after patient allocation into a non-relapsing (NR) group, encompassing those with a single episode of VL, and a relapsing (R) group, encompassing those with disease relapse during the follow-up or even before being enrolled in the study (B).

<p>The black dashed line represents the recommended limit for the establishment of secondary prophylaxis (350 cells/mm³). The red dashed line is the median value of the CD4⁺ T cell counts of the HIV-positive controls (377 cells/mm³). Each symbol represents one patient, and the color refers to the same patient at different stages of follow-up. The horizontal bars represent the median values. 6 mpt: six months post-treatment; 12 mpt: 12 months post-treatment. Asterisks denote a statistically significant difference between the phases of follow-up or between the NR and R groups, *p<0.05; ***p<0.001.</p