Abstract
Background
In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses ...of reservoirs and resistance.
Methods
HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time.
Results
The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus −4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively.
Conclusions
These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants.
Food banks are a symptom of a more extensive pressure for emergency food aid, which was summarised for your government in a report to the Department for Environment, Food and Rural Affairs (DEFRA) ...released this year.4 Food bank numbers are an inadequate indicator of need, because many households only ask for emergency food help as a last resort.
Intermittent (on 4 days per week) antiretroviral therapy (ART) for patients with HIV-1 might be more convenient, better tolerated, and cheaper than continuous treatment. We aimed to establish the ...efficacy and safety of a 4-days-on and 3-days-off (intermittent) maintenance regimen versus a standard 7 day (continuous) maintenance regimen.
In a randomised, open-label, multicentre, parallel, non-inferiority trial, we randomly assigned (1:1) adults with HIV-1 infection with a plasma viral load (pVL) of less than 50 copies per mL for more than 12 months and no drug-resistance mutations to either the intermittent regimen or their existing continuous maintenance regimen, with stratification according to third therapeutic agent (protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or integrase-strand transfer inhibitor). Participants were recruited from 59 hospitals throughout France. The main exclusion criteria were CD4 cell count lower than 250 cells per μL and chronic hepatitis B virus infection. The primary endpoint was the proportion of participants in the modified intention-to-treat (mITT) population who started the study strategy presenting treatment success at week 48 (pVL <50 copies per mL without strategy modification), estimated using the US Federal Drug Administration snapshot approach, with a 5% non-inferiority margin. The study was registered with ClinicalTrials.gov (NCT03256422) and EudraCT (2017-000040-17). The trial is now closed.
From Sept 7, 2017, to Jan 22, 2018, 850 potential participants were screened for eligibility. 647 participants were enrolled and randomly assigned (1:1) to either the intermittent or the continuous treatment group. The mITT population included 636 participants (318 per group). At week 48, in the mITT population, treatment success was recorded in 304 (96%) of 318 participants in the intermittent treatment group and 308 (97%) of 318 in the continuous treatment group (adjusted difference -1·3%, 95% CI -4·2 to 1·7). Six (2%) participants in the intermittent treatment group and four (1%) participants in the continuous treatment group had virological failure. Grade 3-4 adverse events were reported in 29 (9%) participants in the intermittent treatment group and 39 (12%) participants in the continuous treatment group (p=0·320). Daily life satisfaction improved in 153 (59%) of 258 participants in the intermittent treatment group versus 19 (7%) of 255 in the continuous treatment group (p<0·0001). ART costs were 43% lower in the intermittent treatment group than in the continuous treatment group (p<0·0001).
These findings show the non-inferiority of the treatment strategy of 4-consecutive-days-on and 3-days-off strategy maintenance regimen relative to standard continuous ART triple therapy over 48 weeks. 4 days on and off treatment represents a workable, effective alternative strategy for patients with high adherence to ART, and using a drug combination with a high genetic barrier to resistance.
Institut National de la Santé et de la Recherche Médicale Agence Nationale de Recherche sur le Sida et les Hépatites Virales, Maladies Infectieuses Emergentes.
Discusses the goats (Capra aegagrus hircus) and pigs (Sus scrofa) from Auckland Island, and the rabbits (Oryctolagus cuniculus) and cattle (Bos taurus) from Enderby Island, that were rescued during ...eradication programmes on the islands undertaken during the late 20th century and taken to mainland New Zealand with a view to studying and maintaining their particular breeds. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Zusammenfassung
1. Es dient überragenden Gemeinwohlbelangen, die Notfallversorgung in Krankenhäusern zu strukturieren und in ihrer Qualität zu sichern.
2. Der Beschl. des G-BA über die Erstfassung ...der Regelungen zu einem gestuften System von Notfallstrukturen in Krankenhäusern gemäß §136c Abs. 4 SGB V v. 19.4.2018 ist rechtlich nicht zu beanstanden.
3. Belegkrankenhäuser haben keinen Anspruch auf eine Sonderrolle im “System der Notfallstrukturen in Krankenhäusern”; sie werden durch den Beschl. des G-BA v. 19.4.2018 nicht willkürlich gleichbehandelt.
Rietveld refinement techniques have been used to investigate the structural characteristics of CdS window layers at various thicknesses in the current study. The structural parameters were improved ...as the thickness of the CdS-layer was raised, according to XRD patterns. This, in turn, was owing to the increase in the crystal's size for the studied thin layers. For the Ni/n-CdS/i-AgSe/p-CdTe/Pt heterojunction that was successfully fabricated employing an AgSe buffer layer deposited directly on the p-CdTe absorber layer and then the CdS window layer deposited on these mentioned layers, the photovoltaic properties were determined under the dark and illuminated conditions. In dark conditions, from the forward and reverse (current-voltage) data, the essential behavior related to the fabricated devices has been determined. In addition, the heterojunction resistance, the shunt resistance, the series resistance and the rectification rate were all determined. As well, in the illumination case, the open-circuit voltage, the short-circuit current, the fill factor, the power conversion efficiency, (PCE), the photoresponsivity, the quantum efficiency, the dependence of generated photocurrent on the light intensity, the dependence of generated photocurrent on wavelength (λ) for the studied solar cells have been computed and discussed.
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