TALEN-mediated genetic inactivation of the glucocorticoid receptor in cytomegalovirus-specific T cells

Key Points The GR gene can be inactivated in Streptamer-selected CMV-specific CD8+ T cells using TALEN. The GR gene inactivation endows T cells with resistance to the immunosuppressive effects of corticosteroids in vitro and in vivo.</jats:p

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy following anti‐CD19 CAR‐T therapy: a case report

Abstract Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection with few treatment options and poor survival when reversal of the underlying immune dysfunction is not achievable. JC polyomavirus reactivation resulting in PML can rarely complicate chimeric antigen receptor T‐cell (CAR‐T) therapy. We describe successful treatment of PML with Programmed death‐1 (PD‐1) blockade using pembrolizumab, 4 months following axicabtagene ciloleucel. Radiological features of immune reconstitution inflammatory syndrome without clinical deterioration were seen. Evidence of anti‐viral immune reconstitution by in vitro detection of JC‐specific T‐cells and sustained neurological recovery in this patient suggest PD‐1 blockade may be an effective treatment approach for PML post‐CAR‐T

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

BACKGROUND The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe