Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches

Espectro clínico de la Enfermedad de Castleman

RESUMEN La enfermedad de Castleman(EC) es una enfermedad hematológica rara caracterizada por hiperplasia de nódulos linfoides con dos patrones histológicos y clínicos bien diferenciados: hialino-vascular que suele ser unicéntrico, de comportamiento poco agresivo y cuya exeresis consigue la curación en la mayor parte de los casos. La variante plasmocelular es más agresiva, su presentación clínica remeda los linfomas de alto grado y requiere quimioterapia para su erradicación. Juegan un papel etiopatogenico el HVH-8 y las interleucinas IL-6 e IL-1. Nuevos fármacos basados en el bloqueo de la IL-6 o su receptor han demostrado recientemente su utilidad para el control de la enfermedad. Presentamos cuatro casos clínicos que representan el espectro de la EC. ABSTRACT Castleman 's disease (CD) is a rare hematological disease characterized by hyperplasia of lymphoid nodules with two distinct histological and clinical patterns : hyaline - vascular which is usually single-center , low and aggressive behavior which gets exeresis healing in most of cases . The plasma cell variant is more aggressive clinical presentation mimics high-grade lymphomas and requires chemotherapy to eradicate. Play an etiopathogenic role HHV -8 and IL -6 and IL -1 cytokines. New drugs based on the blockade of IL -6 or its receptors have recently proved useful in the control of the disease. We present four cases representing the spectrum of CD