Network Meta-Analysis of Ulcerative Colitis Pharmacotherapies: Carryover Effects from Induction and Bias of the Results

Dear Editor, In their network meta-analyses (NMAs) of treatments for ulcerative colitis (UC), Singh et al1 did not take into account a complication associated with studies that re-randomized patients for the maintenance phase: differential carryover effects from induction can bias the results. In those studies, patients who responded to induction were re-randomized to maintenance treatments that included placebo. If, however, carryover effects from induction differ substantially among active treatments, the effects of those treatments, relative to placebo, are not comparable

HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4+ T Cells

Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+ T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated dendritic cells. Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4+ T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1