Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil-ANRS 12274.

Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), γδ T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a (p = 0.025), NKp80 (p = 0.033), and NKG2C (p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2-24). A higher frequency of the γδ T cell population was observed in the TB/HIV patients with inversion of the Vδ2+/Vδ2- ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular γδ T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and γδ T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6-24). An increase of CD161+ NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients.

Perfil clínico-epidemiológico de pacientes coinfectados por Tuberculose/HIV acompanhados em serviço de referência HIV/aids em Nova Iguaçu, RJ entre 2010-2014 / Clinical and epidemiological profile of patients co-infected by TB/HIV followed up at reference service HIV/AIDS in Nova Iguaçu, RJ between 2010-2014

O vírus da imunodeficiência humana (HIV) associado à tuberculose (TB) permanececomo o maior desafio para a saúde pública global. TB é considerada, atualmente, adoença oportunista mais importante entre os pacientes portadores de HIV/aids nospaíses em desenvolvimento como o Brasil. A coinfecção TB/HIV é um desafio tantopara o seu diagnóstico quanto para o seu tratamento. Objetivo: Estudar a coinfecçãoTB/HIV em pacientes atendidos no Serviço de Assistência Especializada (SAE) emHIV/aids de Nova Iguaçu no período compreendido entre julho de 2010 e junho de2014. Métodos: Estudo retrospectivo realizado entre julho de 2010 e junho de 2014com 127 pacientes coinfectados TB/HIV no Serviço de Assistência Especializada(SAE) em HIV/aids de Nova Iguaçu, no Estado do Rio de Janeiro. Foram analisadosdados referentes às características clínicas, radiológicas e laboratoriais, bem como,às condições de diagnóstico, acompanhamento e finalização dos casos. Osprontuários desses pacientes foram revistos usando formulário especialmenteelaborado para a captura dos dados de interesse do estudo. Casos de síndromeinflamatória de reconstituição imune associada à TB-HIV (TB/IRIS) foram identificadose descritos. Resultados: Dos 127 pacientes estudados 45 (35,4 por cento) tinhamdiagnóstico simultâneo de HIV e 82 (64,6 por cento) tinham diagnóstico não simultâneo deHIV no momento do diagnóstico da TB. Pacientes com diagnóstico não simultâneo deHIV tinham imunossupressão menos avançada do que aqueles com diagnósticosimultâneo de HIV (mediana da contagem CD4: 232 células/µl versus mediana dacontagem CD4: 126 células/µl) no início do tratamento de TB. Isso sugere que odiagnóstico da infecção HIV foi feito muito tardiamente nesse grupo de diagnósticosimultâneo de HIV. A mediana de carga viral inicial foi > 4.0 log10 nos dois grupos depacientes (diagnóstico simultâneo e diagnóstico não simultâneo)...

Background: Immunodeficiency virus (HIV) associated with tuberculosis (TB) remainsa major challenge to global public health. TB is currently considered the most importantopportunistic infectious disease among HIV-1-infected subjects in developingcountries, such as Brazil. Objective: To study the TB/HIV-coinfected patients treatedat the Specialized Care Service (SAE) in HIV/aids in Nova Iguaçu in the periodbetween July 2010 and June 2014. Methods: A retrospective study was conductedbetween July 2010 and June 2014 with 127 patients who were TB/HIV-coinfected, inthe Specialized Care Service (SAE) in HIV/aids Nova Iguaçu, state of Rio de Janeiro.All data related to clinical, radiological and laboratory characteristics, as well as theconditions for HIV/TB diagnosis, follow-up and termination of cases were analyzed. Allthe data of 127 patients were abstracted via chart review using a form especially madefor the study. Additionally, immune reconstitution inflammatory syndrome-TBassociated were identified and described. Results: Of the 127 patients participating inthe study, 45 (35.4 percent) had recent HIV diagnosis and 82 (64.6 percent) were previouslydiagnosed with HIV at the time TB was diagnosed. Patients with a previous HIVdiagnosis had their immunosuppression less advanced than those with recent HIVdiagnosis (median CD4 count 232 cells/µl versus median CD4 count 126 cells/µl). Thissuggests that the diagnosis of HIV infection was made too late in the newly diagnosedgroup with HIV. The median viral load was > 4.0 log10 in both groups of patients (recentand previous diagnosis)...