The importance of early diagnosis for the survival of HIV positive patients

En la Argentina, el diagnóstico del HIV se realiza por solicitud voluntaria de los individuos o a través de la detección de sintomatología asociada a la infección. Sin embargo, debido a la elevada proporción de sujetos portadores que desconocen su estado serológico son necesarias nuevas estrategias. En el presente artículo mostramos cómo un modelo matemático predice el impacto de la expansión de la prueba diagnóstica del HIV en la Argentina. El modelo se basa en matrices de Markov y utiliza probabilidades de transición dependientes de parámetros obtenidos de estudios de cohortes nacionales e internacionales. Las predicciones incluyen tiempo en estadios clínicos y tratamiento, conteo de CD4, carga viral, estadío de infección, edad, tasas de mortalidad y proporción de infección desconocida a nivel poblacional. Las simulaciones se desarrollaron para la situación actual y para un escenario hipotético con diagnóstico más temprano. Mostramos predicciones que sugieren que el diagnóstico realizado antes de la progresión a sida incrementaría la expectativa de vida en unos 10.7 años. También, mostramos cómo la reducción del tiempo al diagnóstico hasta 5 años o menos desde la infección reduciría la tasa de mortalidad en el primer año de HAART de 7.6% a 2.1%, la proporción de infección no reconocida de 43.2% a 23.8% y la proporción de individuos con infección desconocida y que requieren tratamiento de 12% a 0.2%. Basados en estas predicciones resaltamos la importancia de implementar políticas de salud destinadas a detectar la infección por HIV en estadios tempranos en la Argentina.In Argentina, HIV diagnosis is reached by voluntary testing or symptom-based case findings. However, because of the high proportion of infected individuals unaware of their serologic status new strategies are required. In this article we show how a mathematic model predicts the impact of expanding HIV testing in Argentina. The model is based on time-dependent Markov matrixes and applies parameters-dependent transition-probabilities obtained from both national and international cohort studies. Outputs include time on clinical stages and therapy regime, CD4-count, viral-load, infection-state and age; mortality rates and proportion of unidentified infection at a population-level. Simulations were performed for current testing strategy and for a theoretical scenario with earlier diagnosis. We show how our prediction suggests that diagnosis before onset of symptoms would increase life expectancy by 10.7 years. Also, we show how a reduction of time to diagnosis to 5 or less years from infection would reduce mortality rates in the first year of HAART from 7.6% to 2.1%, the proportion of unrecognized infection from 43.2% to 23.8% and the proportion of individuals with unaware infection needing treatment from 12% to 0.2%. Based on this prediction we stress the importance of implementing health policies aimed at detecting HIV infection in early stages in Argentina.Fil: Dilernia, Dario Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mónaco, Daniela Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: César, Carina. Fundación Huésped; ArgentinaFil: Cahn, Pedro. Fundación Huésped; ArgentinaFil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution

Estimation of HIV-testing rates to maximize early diagnosis-derived benefits at the individual and population level

In HIV infection, initiation of treatment is associated with improved clinical outcom and reduced rate of sexual transmission. However, difficulty in detecting infection in early stages impairs those benefits. We determined the minimum testing rate that maximizes benefits derived from early diagnosis.Fil: Dilernia, Dario Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;Fil: Mónaco, Daniela Celeste. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;Fil: Cesar, Carina. Fundación Huésped; Argentina;Fil: Krolewiecki, Alejandro Javier. Fundación Huésped; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Patologia Experimental; Argentina;Fil: Friedman, Samuel R.. National Development and Research Institutes; Estados Unidos de América;Fil: Cahn, Pedro. Fundación Huésped; Argentina;Fil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina

Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina

Objective: Our objective was to estimate primary resistance in an urban setting in a developing country characterized by high antiretroviral (ARV) coverage over the diagnosed population and also by an important proportion of undiagnosed individuals, in order to determine whether any change in primary resistance occurred in the past five years. Design: We carried out a multi-site resistance surveillance study according to WHO HIV resistance guidelines, using a weighted sampling technique based on annual HIV case reports per site. Methods: Blood samples were collected from 197 drug-naive HIV-1-infected individuals diagnosed between March 2010 and August 2011 at 20 HIV voluntary counselling and testing centres in Buenos Aires. Clinical records of enrolled patients at the time of diagnosis were compiled. Viral load and CD4 counts were performed on all samples. The pol gene was sequenced and the resistance profile determined. Phylogenetic analysis was performed by neighbour-joining (NJ) trees and bootscanning analysis. Results: We found that 12 (7.9%) of the 152 successfully sequenced samples harboured primary resistance mutations, of which K103N and G190A were the most prevalent. Non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance mutations were largely the most prevalent (5.9%), accounting for 75% of all primary resistance and exhibiting a significant increase (p =0.0072) in prevalence during the past 10 years as compared to our previous study performed in 1997-2000 and in 2003-2005. Nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor primary resistance were low and similar to the one previously reported. Conclusions: Levels of primary NNRTI resistance in Buenos Aires appear to be increasing in the context of a sustained ARV coverage and a high proportion of undiagnosed HIV-positive individuals. © 2013 Rodriguez-Rodrigues N et al; licensee International AIDS Society.Fil: Rodriguez Rodrigues, Nahuel Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Duran, Adriana. Ministerio de Salud de la Nación; ArgentinaFil: Bouzas, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas F. J. Muñiz; ArgentinaFil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas F. J. Muñiz; ArgentinaFil: Vila, Marcelo. Organizacion Mundial de la Salud; ArgentinaFil: Indyk, Debbie. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Bissio, Emiliano. Ministerio de Salud de la Nación; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Dilernia, Dario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin