Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Overview of T and D-T results in JET with ITER-like wall

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted)

Cost-efficient nearly zero-energy buildings (NZEBs)

The next level of energy performance of new buildings within the European Union will be the Nearly Zero-Energy Building (NZEB). A lot of work has been spent on pilot and demonstration buildings on this and even higher energy performance levels throughout many EU countries. However, most of the high performance buildings realised so far result in additional investment costs when compared to the current national minimum energy performance requirements. The considerably higher investment costs are one of the main barriers to the early application of the NZEB-level in Europe. The EU Horizon 2020 project CoNZEBs works on technical solution sets that result in lower investment costs for NZEBs, bringing the costs close to those of conventional new buildings. The project focus is on multi-family houses. In each of the four participant countries Germany, Denmark, Italy and Slovenia a team of researchers is analysing which sets of market-ready technologies at the building envelope, the services systems for heating, domestic hot water, ventilation and cooling (where required) in combination with renewable energy systems can fulfil the NZEB requirements at lower costs than those incurred by the national mainstream NZEB application. Additional efforts are being spent on the life-cycle costs and the life-cycle analysis of the solution sets, as well as on the impact of future developments of primary energy factors, energy costs and technology efficiencies. Since details of the CoNZEBs work are presented in several additional papers, this document gives an overview of the different tasks and results that are available so far

Cost-efficient nearly zero-energy buildings (NZEBs)

The next level of energy performance of new buildings within the European Union will be the Nearly Zero-Energy Building (NZEB). A lot of work has been spent on pilot and demonstration buildings on this and even higher energy performance levels throughout many EU countries. However, most of the high performance buildings realised so far result in additional investment costs when compared to the current national minimum energy performance requirements. The considerably higher investment costs are one of the main barriers to the early application of the NZEB-level in Europe. The EU Horizon 2020 project CoNZEBs works on technical solution sets that result in lower investment costs for NZEBs, bringing the costs close to those of conventional new buildings. The project focus is on multi-family houses. In each of the four participant countries Germany, Denmark, Italy and Slovenia a team of researchers is analysing which sets of market-ready technologies at the building envelope, the services systems for heating, domestic hot water, ventilation and cooling (where required) in combination with renewable energy systems can fulfil the NZEB requirements at lower costs than those incurred by the national mainstream NZEB application. Additional efforts are being spent on the life-cycle costs and the life-cycle analysis of the solution sets, as well as on the impact of future developments of primary energy factors, energy costs and technology efficiencies. Since details of the CoNZEBs work are presented in several additional papers, this document gives an overview of the different tasks and results that are available so far

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice : A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41-6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain. Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000-2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively. Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2-79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999-2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin. Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics