1. |
|
|
2. |
- Shepherd, L., et al.
(author)
-
Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
-
In: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
-
Journal article (peer-reviewed)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
|
|
3. |
|
|
4. |
- Eron, Joseph J., et al.
(author)
-
Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
- 2019
-
In: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 170
-
Journal article (peer-reviewed)abstract
- © 2019 The Authors Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
|
|
5. |
|
|
6. |
- Athan, E., et al.
(author)
-
Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis
- 2017
-
In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 23, s. 544-549
-
Journal article (peer-reviewed)abstract
- © 2017 European Society of Clinical Microbiology and Infectious Diseases Objectives Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. Methods All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. Results Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). Conclusions In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.
|
|
7. |
|
|
8. |
|
|
9. |
|
|
10. |
|
|
11. |
|
|
12. |
|
|
13. |
|
|
14. |
|
|
15. |
|
|
16. |
|
|
17. |
|
|
18. |
|
|
19. |
|
|
20. |
|
|
21. |
|
|
22. |
|
|
23. |
|
|
24. |
|
|
25. |
|
|