Morbidität und Mortalität der HIV-Infektion

Zusammenfassung: Morbidität und Mortalität von HIV-infizierten Menschen haben seit 1996 aufgrund der antiretroviralen Kombinationstherapie (cART) dramatisch abgenommen. Die HIV-Infektion wurde somit zu einer chronischen, ambulant behandelbaren und meist asymptomatischen Krankheit mit praktisch normaler Lebenserwartung. Ein Hauptgrund der verbleibenden Morbidität und Sterblichkeit ist, dass die HIV-Infektion in etwa 20% der Fälle spät diagnostiziert bzw. therapiert wird. Oft liegt zu diesem Zeitpunkt die CD4-Zellzahl bereits unter der Schwelle von 200Zellen/µl und/oder AIDS-definierende Krankheiten haben sich manifestiert. Weitere Gründe für die verbleibende Morbidität und Mortalität sind Komorbiditäten, insbesondere die Koinfektion mit einer viralen Hepatitis und Tumoren bei älteren Patienten. Durch die verbesserte Prognose nimmt das Alter HIV-infizierter Menschen zu. Dies bedeutet aufgrund von Komorbiditäten und sozioökonomischen Kosten eine erhebliche Herausforderung für die Zukunf

Полифункциональность языковой единицы в формате двуязычного контекста

Предложенный материал показывает взаимосвязь функций языка на примере наименований предприятий конкретного профиля деятельности - кафе и ресторанов Томска. Показана их взаимосвязь, как основа полифункциональности языковой единицы. Интерпретированные языковые средства, которые использованы в названиях в формате двуязычного контекста

Late presentation of HIV infection : a consensus definition

OBJECTIVES: Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection. METHODS: Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition of what is meant by a 'late-presenting' patient. RESULTS: Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/\u3bcL or presenting with an AIDS-defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease: persons presenting for care with a CD4 count below 200 cells/\u3bcL or presenting with an AIDS-defining event, regardless of the CD4 cell count. CONCLUSION: The European Late Presenter Consensus working group believe it would be beneficial if all national health agencies, institutions, and researchers were able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infectio

Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: A pooled analysis of 26 clinical trials

Objective:Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomized trials; however, the comparative incidence of clinically significant renal events remains unclear.Design:We used a pooled data approach to increase the person-years of drug exposure analysed, maximizing our ability to detect differences in clinically significant outcomes.Methods:We pooled clinical renal safety data across 26 treatment-naive and antiretroviral switch studies to compare the incidence of proximal renal tubulopathy and discontinuation due to renal adverse events between participants taking TAF-containing regimens vs. those taking TDF-containing regimens. We performed secondary analyses from seven large randomized studies (two treatment-naive and five switch studies) to compare incidence of renal adverse events, treatment-emergent proteinuria, changes in serum creatinine, creatinine clearance, and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein-to-creatinine ratios).Results:Our integrated analysis included 9322 adults and children with HIV (n = 6360 TAF, n = 2962 TDF) with exposure of 12 519 person-years to TAF and 5947 to TDF. There were no cases of proximal renal tubulopathy in participants receiving TAF vs. 10 cases in those receiving TDF (P < 0.001), and fewer individuals on TAF (3/6360) vs. TDF (14/2962) (P < 0.001) discontinued due to a renal adverse event. Participants initiating TAF-based vs. TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy.Conclusion:These pooled data from 26 studies, with over 12 500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF

Comparison of two reduced-dose regimens of indinavir (600 mg vs 400 mg twice daily) and ritonavir (100 mg twice daily) in healthy volunteers (COREDIR).

Contains fulltext : 58003.pdf (publisher's version ) (Closed access)OBJECTIVE: To assess the pharmacokinetics and tolerability of reduced dosages of twice daily indinavir (IDV) boosted by low-dose ritonavir (RTV) in healthy volunteers. METHODS: Pharmacokinetics and tolerability of IDV/RTV twice daily (600/100 mg and 400/100 mg) were assessed in a randomized crossover design in 16 healthy volunteers. Each dosage was taken twice daily for 2 weeks before 12 h pharmacokinetics were obtained. RESULTS: Sixteen subjects were included, with a mean age +/- SD of 30 +/- 4 years; seven female, nine male. Fifteen subjects completed the study. After dose reduction of IDV AUC, Cmax and Cmin decreased significantly. In the 400 mg group three out of 15 subjects had IDV levels below 0.10 mg/l vs none in the 600 mg group. All subjects reported mild to moderate side effects throughout the study period, which were more severe in the 600 mg group (mostly renal, dry skin/lips, paresthesias/oral discomfort). In the 600 mg group four subjects reported dysuria and one subject discontinued because of flank pain, whereas two subjects reported dysuria and no subject discontinued in the 400 mg group, respectively. Eight subjects developed crystalluria without a significant difference between both groups. No significant change in serum creatinine was observed. CONCLUSIONS: IDV/RTV 400/100 mg twice daily resulted in significant lower IDV exposure, with three out of 15 subjects revealing Cmin values below the recommended threshold for wild-type virus of 0.10 mg/l. Tolerability, however, was lower in the 600 mg IDV group. Therapeutic drug monitoring in the individual patient appears to be necessary to guarantee appropriate drug levels and simultaneously minimize toxicity

Lopinavir/ritonavir plus saquinavir in salvage therapy; pharmacokinetics, tolerability and efficacy.

Item does not contain fulltextPatients receiving a lopinavir/ritonavir and saquinavir dual protease inhibitor-based antiretroviral salvage regimen were studied to evaluate the pharmacokinetics, tolerability and efficacy of the regimen. Pharmacokinetic curves were obtained for lopinavir and saquinavir. Patient records were studied for adverse events and efficacy data. The pharmacokinetics of lopinavir and saquinavir were comparable with literature data, except for the saquinavir 0-12 h area under the curve and maximum concentration. The tolerability of the regimen was good and efficacy was encouraging

Detection of a sexually transmitted hepatitis C virus protease inhibitor-resistance variant in a human immunodeficiency virus-infected homosexual man

There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus–infected men who have sex with men. Transmission of HCV variants that are resistant to recently approved direct-acting antivirals (DAAs) could be an important clinical and public health problem. We document a case of transmission of a DAA-resistant variant of HCV from a patient who was treated with telaprevir to his sexual partner. The transmission of HCV DAA-resistant variants could impair therapeutic regimens that include DAAs