The Potential for DPPIV/CD26 usage as a surrogate marker for Antiretroviral Therapy Efficacy in HIV Infected populations

Background: Human Immunodeficiency Virus (HIV) viral load and CD4+ cell counts are the most commonly used markers for monitoring efficacy of anti-retroviral therapy (ART) in HIV infected individuals. The high cost of viral load monitoring limits its usage in resource limited countries, often leaving the use of CD4+ T cell counts as the only alternative. Though cheaper and more readily available, CD4+ cell counts as a measure of detecting treatment failure, is an unreliable predictor of disease progression. Hence, there is a need for more sensitive alternative, but less costly techniques for detecting treatment failure which can be used in resource limited settings. Objective: To evaluate the feasibility of using plasma CD26/Dipeptidyl peptidase IV (DPPIV) as a novel marker for clinical evaluation of treatment efficacy in HIV infected children. Method: Blood samples collected from HIV+ children (n=76) before and after initiation on ART, were assessed for HIV RNA (viral load), CD4+ T-cell count and DPPIV/CD26 levels. Viral load levels were analyzed using Roche Amplicor HIV-1 Monitor Test kit; CD4+ T-Cell Counts were analyzed using BD FACS Calibur flow cytometer while DPPIV/CD 26 levels were analyzed using Human DPPIV/CD26 Quantikine ELISA kit (R&D Systems, Minneapolis MN). Results: The plasma DPPIV/CD26 levels increased significantly in children after ART initiation (p = 0.017), while the viral load levels declined after ART initiation with subsequent CD4+ cell counts increase. The DPPIV/CD 26 increase positively correlated with viral load decrease while negatively correlating to the CD4+ cell count increase. Conclusion: These findings demonstrate an inverse relationship between DPPIV/CD26 levels and HIV viral load and the direct proportionality of CD4+ Cell counts and DPPIV/CD26 levels, suggesting potential for use of DPPIV/CD26 as a surrogate marker for evaluating HIV disease progression in children receiving anti-retroviral therapy. Key words: CD26/Dipeptidyl peptidase IV (DPPIV), ELISA, Surrogate marker, Viral Load, CD4 Count, antiretroviral

Unique cytokine and chemokine patterns in bronchoalveolar lavage are associated with specific causative pathogen among HIV infected patients with pneumonia in Medellin Colombia

RESUMEN: Queríamos investigar el perfil de citoquinas pro-inflamatorias / quimiocinas asociados con los agentes etiológicos identificados en pacientes con VIH. Los pacientes inmunodeprimidos ingresados ​​en dos hospitales en Medellín, Colombia, con diagnóstico clínico y radiográfico de la neumonía se inscribieron en el estudio. Después de la autorización, se recogió el lavado broncoalveolar (BAL) para bacterias, micobacterias y hongos diagnóstico. Todos los pacientes fueron seguidos durante un año. Una muestra de BAL almacenada se utiliza para la detección de citoquinas / quimioquinas y citoquinas medida usando ensayos comerciales humana, basados ​​en perlas magnéticas 19-plex. El análisis estadístico se realizó mediante la asignación de niveles de concentraciones de citoquinas / quimioquinas en 75 percentil (superior). Se llevaron a cabo análisis de componentes principales (PCA) y el análisis de Kruskal-Wallis para identificar la agrupación de citoquinas con las diversas etiologías infecciosas (hongos, Mycobacterium tuberculosis - BTT, y bacterias). La edad promedio de los pacientes era de 35 años, de los cuales el 77% eran hombres, y la mediana del recuento de CD4 de 33cells / l. De los 57 pacientes infectados por el VIH, la mortalidad hospitalaria fue del 12,3% y el 33% murió dentro de un año de seguimiento. El PCA reveló aumento de IL-10, IL-12, IL-13, IL-17, eotaxina, GCSF, MIP-1α, y las concentraciones de MIP-1 beta que se asocia con la infección MTB. En los pacientes con infección fúngica probada, bajas concentraciones de IL-1RA, IL-8, se identificaron TNF-α y VEGF. Las infecciones bacterianas muestran un patrón de citoquinas distintas y no fueron mal clasificados utilizando los patrones de citoquinas MTB u hongos (valor de p 75 percentile (higher). Principal component analysis (PCA) and Kruskal-Wallis analysis were conducted to identify the clustering of cytokines with the various infectious etiologies (fungi, Mycobacterium tuberculosis - MTB, and bacteria). Average age of patients was 35, of whom 77% were male, and the median CD4 count of 33cells/μl. Of the 57 HIV infected patients, in-hospital mortality was 12.3% and 33% died within a year of follow up. The PCA revealed increased IL-10, IL-12, IL-13, IL-17, Eotaxin, GCSF, MIP-1α, and MIP-1β concentrations to be associated with MTB infection. In patients with proven fungal infection, low concentrations of IL-1RA, IL-8, TNF-α and VEGF were identified. Bacterial infections displayed a distinct cytokine pattern and were not misclassified using the MTB or fungi cytokine patterns (p-value<0.0001). Our results indicate a unique pattern of pro-inflammatory cytokine/chemokine, allowing differentiation between bacterial and non-bacterial pathogens. Moreover, we found distinct, if imperfectly discriminatory, cytokine/chemokine patterns associated with MTB and fungal infections

Atypical bacterial pneumonia in the HIV-infected population

Abstract Human immunodeficiency virus (HIV)-infected individuals are more susceptible to respiratory tract infections by other infectious agents (viruses, bacteria, parasites, and fungi) as their disease progresses to acquired immunodeficiency syndrome. Despite effective antiretroviral therapy, bacterial pneumonia (the most frequently occurring HIV-associated pulmonary illness) remains a common cause of morbidity and mortality in the HIV-infected population. Over the last few decades, studies have looked at the role of atypical bacterial pneumonia (i.e. pneumonia that causes an atypical clinical presentation or responds differently to typical therapeutics) in association with HIV infection. Due to the lack of available diagnostic strategies, the lack of consideration, and the declining immunity of the patient, HIV co-infections with atypical bacteria are currently believed to be underreported. Thus, following an extensive database search, this review aimed to highlight the current knowledge and gaps regarding atypical bacterial pneumonia in HIV. The authors discuss the prevalence of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Coxiella burnetii, Legionella species and others in the HIV-infected population as well as their clinical presentation, methods of detection, and treatment. Further studies looking at the role of these microbes in association with HIV are required. Increased knowledge of these atypical bacteria will lead to a more rapid diagnosis of these infections, resulting in an improved quality of life for the HIV-infected population

Inflammatory Patterns Associated with <i>Legionella</i> in HIV and Pneumonia Coinfections

Legionella infections have a propensity for occurring in HIV-infected individuals, with immunosuppressed individuals tending to present with more severe disease. However, understanding regarding the Legionella host response in immune compromised individuals is lacking. This study investigated the inflammatory profiles associated with Legionella infection in patients hospitalized with HIV and pneumonia in Medellín, Colombia from February 2007 to April 2014, and correlated these profiles with clinical outcomes. Sample aliquots from the Colombian cohort were shipped to Canada where Legionella infections and systemic cytokine profiles were determined using real-time PCR and bead-based technology, respectively. To determine the effect of Legionella coinfection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella-positive and -negative individuals. Principal component analysis revealed higher plasma concentrations of eotaxin, IP-10 and MCP-1 (p = 0.0046) during Legionella infection. Individuals with this immune profile also had higher rates of intensive care unit admissions (adjusted relative risk 1.047 [95% confidence interval 1.027–1.066]). Results demonstrate that systemic markers of monocyte/macrophage activation and differentiation (eotaxin, MCP-1, and IP-10) are associated with Legionella infection and worse patient outcomes. Further investigations are warranted to determine how this cytokine profile may play a role in Legionella pneumonia pathogenesis or immunity