An open-label phase 1 clinical trial of the anti-αβ monoclonal antibody vedolizumab in HIV-infected individuals.

Despite the substantial clinical benefits of antiretroviral therapy (ART), complete eradication of HIV has not been possible. The gastrointestinal tract and associated lymphoid tissues may play an important role in the pathogenesis of HIV infection. The integrin αβ facilitates homing of T lymphocytes to the gut by binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on venules in gut-associated lymphoid tissue.

Total body CD4+ T cell dynamics in treated and untreated SIV infection revealed by in vivo imaging.

The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of lymph nodes within the same host.

Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures: PREVAIL II, the Ebola MCM Study.

Background: Unique challenges posed by emerging infectious diseases often expose inadequacies in the conventional phased investigational therapeutic development paradigm. The recent Ebola outbreak in West Africa presents a critical case-study highlighting barriers to faster development. During the outbreak, clinical trials were implemented with unprecedented speed.

State-of-the-Art Workshops on Medical Countermeasures Potentially Available for Human Use Following Accidental Exposures to Ebola Virus.

The ongoing outbreak of Ebola in West Africa has raised a general awareness that at present there are no Ebola-specific medical countermeasures (MCMs) with proven effectiveness. This paper recapitulates discussions held at the 6th International Filovirus Symposium in March 2014 as well as the subsequent design of a randomized clinical trial design for treating Ebola virus-infected patients evacuated from West Africa to the United States. A number of different drugs or biologics were critically reviewed and 3 different postexposure strategies were identified as being farthest along in development; passive immunotherapy with monoclonal antibodies, postexposure vaccination with constructs involving viral vectors (such as vesicular stomatitis virus), and antisense compounds directly targeting the viral genome such as modified phosphorodiamidate morpholino oligomer-based compounds and small interfering RNA products.

Interleukin-2 cycling causes transient increases in high-sensitivity C-reactive protein and D-dimer that are not associated with plasma HIV-RNA levels.

Objective: To determine the effects of interleukin (IL)-2 treatment on inflammatory and thrombotic biomarkers in chronically HIV-infected adults receiving antiretroviral therapy.

Methods: Cryopreserved plasma was evaluated retrospectively for C-reactive protein (CRP) and D-dimer at baseline, end of an IL-2 cycle, and long-term follow up from two randomized, controlled trials: 57 IL-2-naive adults receiving either three to six cycles of IL-2 as well as antiretroviral therapy (nucleoside analogues) or antiretroviral therapy alone for 12 months, and 40 IL-2-experienced adults on highly active antiretroviral therapy who either interrupted or continued therapy for 6 months after a baseline IL-2 cycle. High-sensitivity CRP (hsCRP) was measured by immunonephelometry (detection limit 0.

Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trial.

Objective: To evaluate whether interleukin (IL)-2 in patients with chronic HIV infection can maintain CD4 T cell counts during 6 months of HAART interruption.

Design: Prospective, randomized, controlled, open-label phase II noninferiority trial comparing IL-2 with HAART interruption or continuous HAART.

Methods: Forty-one IL-2-experienced (three or more prior cycles) HIV-1-infected adults with CD4 cell count at least 500 cells/microl were randomized in the ratio 2: 1 to interrupted (I = 27) or continuous (C = 14) HAART for 6 months following an initial IL-2 cycle.