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

• Published in: PloS one 2016-12, Vol.11 (12), p.e0167512-e0167512
• Main Authors: Silva-Freitas, Maria Luciana, Cota, Glaucia Fernandes, Machado-de-Assis, Talia S, Giacoia-Gripp, Carmem, Rabello, Ana, Da-Cruz, Alda M, Santos-Oliveira, Joanna R
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Analysis; Antibodies, Protozoan - immunology; Antiretroviral agents; Antiretroviral drugs; Bacteria; Bacterial Translocation - immunology; Biology and Life Sciences; Care and treatment; CD14 antigen; CD4 antigen; CD4 Lymphocyte Count; Cell activation; Coinfection; Control; Development and progression; Disease Progression; Dosage and administration; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - complications; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humans; Immunity; Immunoglobulin G; Immunoglobulin G - immunology; Immunology; Immunosenescence; Influence; Leishmania; Leishmania donovani; Leishmaniasis, Visceral - etiology; Leishmaniasis, Visceral - parasitology; Lentivirus; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Microorganisms; Parasite Load; Parasitic diseases; Patients; Prophylaxis; Recovery (Medical); Recurrence; Research and Analysis Methods; Retroviridae; T cells; T-Lymphocyte Subsets - immunology; Therapy; Translocation; Vector-borne diseases; Viral Load; Visceral leishmaniasis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167512

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.