Emergence of acquired HIV-1 drug resistance has almost been stopped in Switzerland - a 15 year prospective cohort analysis

BACKGROUND  Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS  We included 11,084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of at least one major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on patient's risk of harboring drug resistant viruses. RESULTS  The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of three-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSION  HIV-1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the pre-combination ART era. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice.

Colorectal cancer (CRC) develops through a multistep process and is modulated by inflammation. However, the inflammatory pathways that support intestinal tumors at different stages remain incompletely understood. Interleukin (IL)-33 signaling plays a role in intestinal inflammation, yet its contribution to the pathogenesis of CRC is unknown. Using immunohistochemistry on 713 resected human CRC specimens, we show here that IL-33 and its receptor ST2 are expressed in low-grade and early-stage human CRCs, and to a lesser extent in higher-grade and more advanced-stage tumors. In a mouse model of CRC, ST2-deficiency protects from tumor development. Moreover, bone marrow (BM) chimera studies indicate that engagement of the IL-33/ST2 pathway on both the radio-resistant and radio-sensitive compartment is essential for CRC development. Mechanistically, activation of IL-33/ST2 signaling compromises the integrity of the intestinal barrier and triggers the production of pro-tumorigenic IL-6 by immune cells. Together, this data reveals a tumor-promoting role of IL-33/ST2 signaling in CRC.

Aus lichteren Tagen : mit ungedruckten Briefen Anastasius Grüns und Ludwig Augus Frankls

Ludwig August Frankl

Aus lichteren Tagen : mit ungedruckten Briefen Anastasius Grüns und Ludwig Augus Frankls

Ludwig August Frankl

Aus lichteren Tagen : mit ungedruckten Briefen Anastasius Grüns und Ludwig Augus Frankls

Ludwig August Frankl

Zum Problem der jüdisch-arabischen "Einheitsorganisation"

Chajim Viktor Arlosoroff

Boden- und Immigrationspolitik im Shaw-Bericht

Chajim Viktor Arlosoroff

Probleme der Finanzierung des Palästina-Aufbaues : Referat

Chajim Viktor Arlosoroff

Hebräische Spruchweisheit

Viktor Klemperer

Der Bissen Brot : Text zur vorstehenden Melodie

Viktor Klemperer

"Das sind deine Götter!" : eine Fieberphantasie

Viktor Klemperer

[Rezension]

Viktor Klemperer

Die Fähre : (Text zur vorstehenden Melodie)

Viktor Klemperer

Arthur Schnitzler

Viktor Klemperer

Der Graf von Charolais

Viktor Klemperer