RESUMEN
BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.
Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Monoclonales/uso terapéutico , BiomarcadoresRESUMEN
Delayed processing of peripheral blood or peripheral blood mononuclear cell isolation and cryopreservation can lead to the detection of somewhat higher levels of CD31 expression on naïve CD4 T cells by flow cytometry. These observations should be considered in the planning of multicenter clinical trials and in the interpretation of the results of functional studies.
Asunto(s)
Conservación de la Sangre , Linfocitos T CD4-Positivos/inmunología , Seropositividad para VIH/inmunología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Adulto , Recolección de Muestras de Sangre , Recuento de Linfocito CD4 , Criopreservación , Seropositividad para VIH/virología , Humanos , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/inmunología , Factores de TiempoRESUMEN
An accurate and reproducible CD4 count is a fundamental clinical tool for monitoring and treating human immunodeficiency virus infection and its complications. Two methods exist for calculating absolute CD4 counts: dual-platform technology (DPT) and single-platform technology (SPT). Numerous studies have documented the unacceptably wide range of variation in absolute CD4 counts between laboratories. SPT was introduced in 1996 to reduce the interlaboratory variation in absolute CD4 counts. The aim of this study was to compare DPT with the BD Biosciences Trucount method (an SPT method). Both the percentages of CD4 (r = 0.986; P = 0.0541) and the absolute CD4 counts (r = 0.960; P = 0.0001) had very good correlation between the two methods. However, poor correlation was observed for the CD8(+) RO(-) (r = 0.314; P = 0.0002), CD8(+) DR(+) (r = 0.666; P = 0.0138), CD3(+) CD38(+) (r = 0.8000; P = 0.0004), CD3(+) CD25(+) (r = 0.464; P = 0.0082), and CD4(+) CD38(+) (r = 0.357; P = 0.0127) measurements.
Asunto(s)
Inmunofenotipificación/métodos , Inmunofenotipificación/normas , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Biomarcadores/análisis , Linfocitos T CD4-Positivos/química , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Humanos , Activación de Linfocitos/inmunología , Subgrupos Linfocitarios/químicaRESUMEN
BACKGROUND: The interleukin-7 (IL-7)/IL-7 receptor alpha (IL-7Ralpha) system is an important regulator of T-cell homeostasis. We evaluated the IL-7/IL-7Ralpha system in a large cohort of HIV-infected patients, including a subset treated with intermittent IL-2. METHODS: IL-7 serum levels and CD127 (IL-7Ralpha) expression on T cells were evaluated in a cross-sectional study of 36 healthy volunteers, 151 HIV-infected patients, and 83 HIV-infected patients who had received IL-2 therapy. Multivariate regression models were used to determine predictors of CD127 expression. RESULTS: HIV-infected patients had higher IL-7 levels compared with healthy volunteers (P = 0.022) and IL-2-treated patients (P = 0.012). CD127 expression was significantly lower on CD4 and CD8 T cells of HIV-infected patients compared with healthy volunteers (P = 0.008 and P < 0.001, respectively), and CD127 median fluorescence intensity was lowest on CD4 T cells in IL-2-treated patients (P < 0.001 compared with HIV-infected patients). The proportion of naive and effector memory/effector T cells were significant predictors of CD127 expression on T cells. IL-2 immunotherapy led to the expansion of a CD25/CD127-low subset of CD4 T cells. CONCLUSIONS: CD127 expression on T cells remains low in HIV-infected patients despite antiretroviral therapy, reflecting persistent aberration in the subset composition of the T-cell pool.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Interleucina-2/uso terapéutico , Receptores de Interleucina-7/biosíntesis , Linfocitos T/inmunología , Adulto , Anciano , Terapia Antirretroviral Altamente Activa , Femenino , Citometría de Flujo , Humanos , Interleucina-7/sangre , Subgrupos Linfocitarios/inmunología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Receptores de Interleucina-2/análisis , Estadística como Asunto , Linfocitos T/virologíaRESUMEN
Decreases in the detection of CD127 expression on T cells of human immunodeficiency virus-infected patients by flow cytometry can occur by delayed processing or by peripheral blood mononuclear cell isolation and cryopreservation. These observations should be considered in the interpretation of functional studies and the planning of multicenter clinical trials.
Asunto(s)
Artefactos , Citometría de Flujo , Infecciones por VIH/inmunología , Receptores de Interleucina-7/biosíntesis , Linfocitos T/inmunología , Adulto , Anciano , Separación Celular/métodos , Criopreservación , Humanos , Persona de Mediana Edad , Factores de TiempoRESUMEN
To evaluate the relationship between T cell turnover, immune activation, and CD4 recovery in HIV infection, 32 antiretroviral-naive HIV-1-infected patients were studied before and after initiation of highly active antiretroviral therapy (HAART). Elevated CD4 and CD8 T cell turnover (measured by Ki67) in HIV infection decreased with HAART in blood and lymphoid tissue. Increased peripheral CD4 T cell turnover was strongly associated with immune activation even after viral suppression to less than 50 copies/mL (R = 0.8; p <.001). Increased CD4 T cell turnover correlated strongly with CD4 cell counts both before (R = -0.6; p <.001) and after (R = -0.4; p =.05) HAART. In patients with baseline CD4 cell counts of less than 350/microL, decreases in CD4 T cell turnover with HAART significantly correlated with increases in CD4 cell counts. In addition, persistently elevated levels of CD4 T cell turnover after HAART were associated with incomplete CD4 T cell recovery despite HIV RNA levels of less than 50 copies/mL. These data suggest that immune activation is central to CD4 cell depletion in HIV infection and immune reconstitution with HAART.