Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.Fil: Falivene, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Socías, María Eugenia. Fundación Huésped; ArgentinaFil: Holgado, María Pía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ruiz, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Maeto, Cynthia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Figueroa, María Inés. Fundación Huésped; ArgentinaFil: Giavedoni, Luis D.. Texas Biomedical Research Institute; Estados UnidosFil: Cahn, Pedro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina. Fundación Huésped; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Sued, Omar Gustavo. Fundación Huésped; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Gherardi, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1) expression) of the CD8+ T-cell subset found in primary HIV infection (PHI) was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM) cells over fully differentiated terminal effector CD8+ T (TTE) cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE) ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the instauration of early interventions to prevent irreversible immune damage.Fil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Falivene, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ruiz, Maria Juliz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Laufer, Natalia Lorna. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Socías, María Eugenia. Fundación Huésped; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Cahn, Pedro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina. Fundación Huésped; ArgentinaFil: Giavedoni, Luis. Southwest National Primate Research Center; Estados UnidosFil: Sued, Omar Gustavo. Fundación Huésped; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Gherardi, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

<p>Abstract</p> <p>Background</p> <p>Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial.</p> <p>Methods</p> <p>Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm³, B, C events or death) at 12 months among untreated patients.</p> <p>Results</p> <p>Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm³, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively.</p> <p>Conclusions</p> <p>In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.</p

Access to health care among women sex workers in Vancouver, Canada : universal health coverage in a criminalized sex work environment

Background: Universal access to health care is a critical determinant of health. Despite the numerous health inequities faced by women sex workers, research on access to health services among this population remains limited, particularly on the role of social-structural factors. This thesis sought to investigate sex workers experiences along the continuum of health care access in a setting with universal health coverage. Methods: Data was dawn from “An Evaluation of Sex Workers’ Health Access”(AESHA), an open prospective cohort of women sex workers in Vancouver, Canada. Logistic regression analyses were employed to evaluate correlates of institutional barriers to care (using generalized estimating equations for longitudinal data), and to assess baseline engagement in the HCV continuum of care. Extended cox regression analyses, with a confounder model approach, were used to examine the independent effect of depot medroxyprogesterone on HSV-2 acquisition. Results: These analyses demonstrated inequities faced by sex workers all along the continuum of health care access, from trying to reach health services (Chapter 2), to utilizing these services (Chapter 3), to the impacts of inadequate and sub-optimal care on their health outcomes (Chapter 4). Among 723 participants, 70.4% reported institutional barriers to health care, only half (52.9%) of 552 HCV-seronegative participants having a recent HCV test, and less than 1% of the 302 women living with HCV receiving treatment. Further, high incidence rates of HSV-2 were documented, with depot medroxyprogesterone use independently associated with approximately 4-times increased risk. Importantly, barriers to care appeared to be exacerbated among most vulnerable women, including sexual/gender minorities, migrants, women of Aboriginal Ancestry, uninsured and those with previous experiences of violence. Conclusions: Findings from this research revealed systemic and persistent barriers to appropriate and quality care among sex workers, highlighting the crucial role played by structural factors in shaping their health care seeking patterns and outcomes. These results further underscore the need to explore new models of care, as well as broader institutional and legal changes to fulfill women sex workers health and human rights, and fully realize the aims of the Canadian universal health system.Graduate and Postdoctoral StudiesGraduat

Correlación entre la prevalencia de uncinarias y strongyloides stercoralis: ¿Una nueva herramienta diagnóstica en salud pública?

Strongyloides stercoralis y uncinarias, cuyas principales especies son Necator americanus y Ancylostoma duodenale, presentan coincidencias en sus características biológicas y epidemiológicas; la infección ocurre cuando las larvas que se encuentran en suelos contaminados con materia fecal penetran la piel intacta, presentan superposición geográfica y el rango de edad de los infectados es similar. Sin embargo, el diagnóstico de S. stercoralis es más desafiante que el de uncinarias, lo que contribuye a que la prevalencia de S. stercoralis sea desconocida y mayormente subestimada. Por lo tanto, nuestra hip´otesis es que la prevalencia de uncinarias (PUn), cuyo diagnóstico es más simple en el laboratorio, podría resultar predictiva de la prevalencia de S. stercoralis (PSt). El objetivo de este trabajo fue investigar la correlación de PUn con PSt. Se realizó una revisión sistemática de trabajos científicos publicados entre los a˜nos 2014 y 2018. Se efectuó una búsqueda en Pubmed, Embase, CAB, LILACS y sciELO con las palabras clave “Hookworm”“Ancylostoma”“Necator”“Strongyloides”“Uncinarias”y “Estrongyloides”. Dicha búsqueda brindo 400 citas. Estas fueron revisadas por dos revisores mediante un análisis de título y resumen. Se tuvieron en cuenta los siguientes criterios de inclusión: trabajos en humanos asintomáticos, diagnóstico parasitológico de referencia y PCR, edad, sexo y raza indistinta pero residentes del lugar, estudios epidemiológicos transversales con prevalencia basales de uncinarias y S. stercoralis. Se seleccionaron 147 trabajos que fueron analizados teniendo en cuenta el texto completo. Finalmente se confirmó la validez y disponibilidad de datos para 41 trabajos que reportaron 42 poblaciones distintas. Los datos se analizaron usando regresión lineal y la correlación de Pearson. Se consideró PUn como la variable independiente y PSt como variable dependiente. Se encontró una correlación significativa entre ambas prevalencias (Pearson = 0.73, P<0.0001), siendo ambas directamente proporcionales (r2= 0.53 P<0.0001). De esta manera, nuestros resultados sugieren que se podría estimar PSt con la función lineal PSt= 0.49x PUn+ 0.49. De confirmarse estos hallazgos con datos experimentales, esta ecuación podría sumarse como una herramienta de gran utilidad para determinar la Pst, y de este modo diseñar estrategias diagnósticas y terapéuticas que incluyan a S. stercoralis.Fil: Fleitas, Pedro Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Socías, María Eugenia. University of British Columbia; Canadá. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Travacio, Marina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Cimino, Rubén Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaXXX Reunión de la Sociedad Argentina de ProtozoologíaResistenciaArgentinaSociedad Argentina de Protozoologí

Acute HIV Seroconversion Presenting with Active Tuberculosis and Associated with High Levels of T-Regulatory Cells

A patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patient high levels of T-regulatory cells (Tregs) and a low proliferation response to M. tuberculosis were initially detected, which normalized throughout follow-up. This case calls for the consideration of tuberculosis in patients in the early stages of HIV, and emphasizes the need for further study of the potential causal relationship between Treg cells and the risk of TB reactivation in HIV patients.Fil: Sued, Omar Gustavo. Fundación Huésped; ArgentinaFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Socías, María Eugenia. Fundación Huésped; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Cahn, Pedro. Fundación Huésped; Argentin

Towards full citizenship: correlates of engagement with the gender identity law among transwomen in Argentina.

In May 2012, Argentina passed its "Gender Identity" Law, which aimed to address the legal invisibility, discrimination and marginalization that transgender individuals have historically faced. The aim of this study was to explore factors associated with engagement with the Gender Identity Law among transwomen living in Argentina.Data were derived from a 2013 nationwide, cross-sectional study involving transwomen in Argentina. Using multivariate logistic regression, we assessed the prevalence and factors associated with acquiring a gender-congruent identity card within the first 18 months of enactment of the Gender Identity Law.Among 452 transwomen, 260 (57.5%) reported that they had obtained a new gender-congruent identity card. In multivariate analysis, factors positively associated with acquiring a new ID were: previously experiencing discrimination by healthcare workers (adjusted odd ratio [aOR] = 2.01, 95% CI: 1.27-3.20); having engaged in transition procedures (aOR = 3.06, 95% CI: 1.58-5.93); and having a job other than sex work (aOR = 1.81, 95% CI: 1.06-3.10). Foreign born transwomen were less likely to have obtained a new ID (aOR = 0.14, 95% CI: 0.06-0.33).More than half of transwomen in our sample acquired a new gender-congruent ID within the first 18 months of enactment of the Gender Identity Law. However, access to and uptake of this right has been heterogeneous. In particular, our findings suggest that the most empowered transwomen may have been among the first to take advantage of this right. Although educational level, housing conditions, HIV status and sex work were not associated with the outcome, foreign-born status was a strong negative correlate of new ID acquisition. Therefore, additional efforts should be made in order to ensure that benefits of this founding policy reach all transwomen in Argentina

Early skewed distribution of total and HIV-specific CD8+ T-cell memory phenotypes during primary HIV infection is related to reduced antiviral activity and faster disease progression.

The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1) expression) of the CD8+ T-cell subset found in primary HIV infection (PHI) was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM) cells over fully differentiated terminal effector CD8+ T (TTE) cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE) ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the instauration of early interventions to prevent irreversible immune damage