Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis.

HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.

Implementación de la estrategia 90-90-90 en un municipio del conurbano bonaerense / Implementation of the 90-90-90 strategy in a municipality in the suburbs of Buenos Aires

INTRODUCCION El tratamiento del VIH es una herramienta fundamental para acabar con la epidemia de SIDA; depende en gran medida de la capacidad de proporcionar acceso universal al tratamiento para el VIH a todos aquellos que lo necesiten. Para ello, la Organización Mundial de la Salud ha propuesto la implementación de la "Estrategia 90-90-90" (E90), la cual consiste en una serie de medidas que permitirían terminar con la epidemia de SIDA en el año 2030; que el 90% de las personas que viven con el VIH (PVVIH) conozcan su diagnóstico, que el 90% de las PVVIH estén recibiendo tratamiento antirretroviral (TARV) y que en 2020 el 90% de las personas que reciben terapia antirretroviral tengan supresión viral. OBJETIVO Aumentar el porcentaje de PVVIH con carga viral indetectable implementando una serie de medidas basadas en la Estrategia 90/90/90 (SM90) en el municipio de Florencio Varela, Buenos Aires. MÉTODOS Se realizó un estudio de intervención, de diseño prospectivo, con aplicación de una serie de medidas basadas en la "Estrategia 90-90-90" (SM90) con tres fases; pre intervención, intervención y de resultados. RESULTADOS Se incluyeron en el estudio 213 pacientes. Se logró aumentar el porcentaje de personas con carga viral indetectable en un 10%. El valor pre intervención fue de 59,37% (95/160) y el de post intervención fue 69,82% (118/169), con una p=0,05 (estadísticamente significativo); OR; 0,63; IC 95; 0,4-0.99. DISCUSIÓN La SM90, puede ser implementada en nuestro país, pudiendo reducirse el número anual de nuevas infecciones por VIH y el número de muertes relacionadas con el SIDA. Es importante trabajar la vinculación, fortaleciendo la relación médico-paciente para generar adherencia al tratamiento antirretroviral, siendo fundamental el abordaje transdisciplinario. La sostenibilidad a largo plazo de estas medidas, tal como lo plantea la E90, lograría mejores resultados

Expansion of CD25-Negative Forkhead Box P3-Positive T Cells during HIV and Mycobacterium tuberculosis Infection.

Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4+CD25-FoxP3+ Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4+CD25+FoxP3+ Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg. Also, IL-10, TGF-ß, IFN-γ production, and the suppressor capacity of uTregs were analyzed in cocultures with effector lymphocytes and compared with the effect of regulatory T cells (Tregs). We found diminished expression of CD39 and higher levels of PD1 on uTreg compared to cTreg in both HIV-TB and healthy donors (HD). In addition, uTreg and cTreg showed differences in maturation status in both HIV-TB and HD groups, due to the expansion of effector memory uTregs. Interestingly, both HIV-TB and HD showed a pronounced production of IFN-γ in uTreg population, though no significant differences were observed for IL-10 and TGF-ß production between uTreg and cTreg. Moreover, IFN-γ+ cells were restricted to the CD39- uTreg population. Finally, when the suppressor capacity was evaluated, both uTreg and cTreg inhibited polyclonal T cell-proliferation and IFN-γ production in a similar extent. These findings suggest that uTregs, which are expanded during HIV-TB coinfection, exert regulatory functions in a similar way to cTregs despite an altered surface expression of Treg characteristic markers and differences in cytokine production.

HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.

Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8(+) T cells, and their modulation by DHEA during HIV-TB coinfection. CD8(+) T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8(+) T cells. Notably, CD8(+) T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RA(dim) proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8(+) T cells from HIV-TB patients increased although restricted to the CD27(+) population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8(+) T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8(+) T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8(+) T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8(+) T-cell functions during HIV-TB coinfection.

Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

Brote de dengue autóctono en el área metropolitana Buenos Aires: Experiencia del Hospital de Enfermedades Infecciosas F. J. Muñiz / Outbreak of indigenous dengue in the Buenos Aires Metropolitan Area: Experience of the F.J. Muñiz Hospital

Como consecuencia de la epidemia de dengue que afectó a la República de Bolivia y provincias del norte argentino, se produjo por primera vez un brote de dengue autóctono en el Area Metropolitana Buenos Aires. A partir de enero de 2009 asistimos casos de dengue importado hasta la tercera semana de marzo, cuando aparecieron los primeros casos por transmisión local, tendencia que se mantuvo hasta mediados de mayo. La mayor concentración de casos autóctonos atendidos residía en la región oeste de la ciudad de Buenos Aires y en localidades de los partidos de 3 de Febrero y La Matanza, que limitan con ella. Existieron factores concurrentes para que se produjera este brote: alta densidad vectorial, viajeros provenientes de regiones epidémicas concentrados por su domicilio en las áreas donde luego se produjo la transmisión local. El 95% ingresaron en los primeros días de viremia y en un período climático caracterizado por temperaturas medias elevadas que se mantuvieron hasta mediados de otoño. De los nueve pacientes con signos de alarma para el desarrollo de dengue grave, siete fueron casos autóctonos que no tenían antecedentes de haber padecido previamente dengue. Se comunican los hallazgos clínicos y epidemiológicos y se analizan los factores que regularon la transmisión.

As a consequence of the dengue epidemic in the Bolivian Republic and the northern provinces of Argentina, an outbreak of indigenous dengue occurred for the first time in the Buenos Aires Metropolitan Area. Since January 2009 we assisted imported dengue cases coming from epidemic regions; later, around the end of March, and until middle autumn, indigenous cases appeared. The major concentration of these indigenous cases was in the west area of Buenos Aires City and in the neighboring localities 3 de Febrero and La Matanza. There were several factors that made the local transmission possible: a high vector density, people traveling from epidemic areas and clustering in the geographical zone where the indigenous epidemic occurred, during a period with high medium temperatures, entering 95% of the imported cases during the first days of the viremia. Of the nine patients with alarming signs for the development of severe dengue, seven were indigenous cases with no previous history of dengue infections. We report the clinical and epidemiological findings, and we analyze the factors which regulated the transmission.

Reactivación de tuberculosis pulmonar asociada a seroconversión al virus de inmunodeficiencia humana / Reactivation of Pulmonary Tuberculosis associated with Human Immunodeficiency Virus (HIV) seroconversion

Entre un 40-90% de los pacientes que adquieren la infección por HIV presentan un conjunto de síntomas durante el periodo de la seroconversión, habitualmente denominado "Síndrome Retroviral Agudo" (SRA)...

It is estimated that between 40 and 90% of HIV infected patients experience some sympotoms during HIV seroconversion, attributable to an acute retroviral syndrome (ARS)...

Reactivación de tuberculosis pulmonar asociada a seroconversión al virus de inmunodeficiencia humana / Reactivation of Pulmonary Tuberculosis associated with Human Immunodeficiency Virus (HIV) seroconversion

Entre un 40-90% de los pacientes que adquieren la infección por HIV presentan un conjunto de síntomas durante el periodo de la seroconversión, habitualmente denominado "Síndrome Retroviral Agudo" (SRA)...(AU)

It is estimated that between 40 and 90% of HIV infected patients experience some sympotoms during HIV seroconversion, attributable to an acute retroviral syndrome (ARS)...(AU)

[Outbreak of indigenous dengue in the Buenos Aires Metropolitan Area. Experience of the F. J. Muñiz Hospital]. / Brote de dengue autóctono en el área metropolitana de Buenos Aires. Experiencia del Hospital de Enfermedades Infecciosas F. J. Muñiz.

As a consequence of the dengue epidemic in the Bolivian Republic and the northern provinces of Argentina, an outbreak of indigenous dengue occurred for the first time in the Buenos Aires Metropolitan Area. Since January 2009 we assisted imported dengue cases coming from epidemic regions; later, around the end of March, and until middle autumn, indigenous cases appeared. The major concentration of these indigenous cases was in the west area of Buenos Aires City and in the neighboring localities 3 de Febrero and La Matanza. There were several factors that made the local transmission possible: a high vector density, people traveling from epidemic areas and clustering in the geographical zone where the indigenous epidemic occurred, during a period with high medium temperatures, entering 95% of the imported cases during the first days of the viremia. Of the nine patients with alarming signs for the development of severe dengue, seven were indigenous cases with no previous history of dengue infections. We report the clinical and epidemiological findings, and we analyze the factors which regulated the transmission.