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Correction to: Infection (2020) 48:723–733 https://doi.org/10.1007/s15010-020-01469-6. The original version of this article unfortunately contained a mistake. In this article the authors Dirk Schürmann at affiliation Charité, University Medicine, Berlin, Olaf Degen at affiliation University Clinic Hamburg Eppendorf, Hamburg and Heinz-August Horst at affiliation University Hospital Schleswig–Holstein, Kiel, Germany were missing from the author list. The original article has been corrected.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
The thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to the effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interfered with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and the addition of Fe3+ prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after hematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses, and synergistically increase the effects of ganciclovir, eltrombopag is also a drug-repurposing candidate for the treatment of therapy-refractory HCMV diseas.
Der Fischadler (pandion haliaefus), der nahezu weltweit verbreitet ist, kommt in Deutschland vorwiegend im Nordosten als Brutvogel vor. Er ernährt sich fast ausschließlich von lebend erbeuteten Fischen. Bis Mitte des 20. Jahrhunderts wurde er deshalb in vielen Teilen Europas als vermeintlicher Nahrungskonkurrent des Menschen verfolgt und ausgerottet (z. B. SCHMIDT 1995a). Weitere Bestandseinbußen erlitt der Fischadler in den 1960er und 70er Jahren durch Kontamination mit den auf land- und forstwirtschaftlichen Flächen ausgebrachten Pestiziden, vornehmlich DDT. Das führte zur Dünnschaligkeit und zum Bruch der Eier. Seine dadurch über eine lange Zeit bedingte Seltenheit führte bei Ornithologen und Naturschützern zu der Annahme, der Fischadler sei eine scheue und anspruchsvolle Vogelart. Schutzmaßnahmen in den mitteleuropäischen Kerngebieten seiner Verbreitung, in Mecklenburg und Brandenburg, haben in den vergangenen 20 Jahren zu einer deutlichen Bestandserholung geführt. So kommt es jährlich zu neuen Ansiedlungen auch in Regionen, die den bisherigen Vorstellungen über den von dieser Vogelart bevorzugten Lebensraum kaum entsprechen. Im Folgenden soll über eine Ansiedlung des Fischadlers im Landkreis Bitterfeld berichtet werden. Diese Region war einerseits einer hohen Umweltbelastung durch chemische Industrie und Braunkohletagebau ausgesetzt, andererseits existieren aber auch noch Reste von fast ursprünglichen Naturräumen, und es wurde durch menschliches Wirken eine "Natur aus zweiter Hand" geschaffen. Besonderes Augenmerk wird bei diesen Ausführungen auf praktische Artenschutzmaßnahmen gelegt, die dem Fischadler die Ansiedlung zur Brut in einer Bergbaufolgelandschaft ermöglicht haben.