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Introduction Despite the life-prolonging effects of Highly Active Antiretroviral Therapy (HAART), persons with HIV are still prone to higher rates of non-AIDS related morbidity (such as heart, kidney, and liver disease) than the general public. This is likely due to chronic immune activation and inflammation that persists in HIV-positive persons despite virological suppression. What remains undetermined, however, is whether a link exists between chronic inflammation/immune activation and suboptimal immune recovery on HAART. The hypothesis of the present study is that higher levels of systemic subclinical inflammation and immune activation are linked with suboptimal immune recovery on HAART. Methods Fifteen eligible patients from the Manitoba HIV program were enrolled and followed for up to two years; blood samples were drawn at 4 timepoints each, and concentrations of 21 proinflammatory markers were measured. Patients were grouped according to CD4:CD8 recovery at viral suppression, and the inflammatory profiles of the two groups were compared. Results and conclusions APRIL and BAFF are higher in those with poor recovery at the point of viral suppression, but were also higher in this group at the onset of therapy and through the three additional follow-up visits. TNF-R1, CD163, and Osteopontin, were also in higher concentrations at the outset of therapy and beyond. These five molecules could thus see potential use in the future as biomarkers of likely poor immune recovery. Future work should focus on replicating these findings with larger cohorts.

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