Immediate vs. deferred switching from a boosted protease inhibitor (PI/r) based regimen to a Dolutegravir (DTG) based regimen in virologically suppressed patients with high cardiovascular risk or Age ≥50 years: final 96 weeks results of NEAT 022 study

Background Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)–based regimen to a dolutegravir (DTG)–based regimen may improve lipid profile. Methods European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)–infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). Results Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, –.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile

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

Results of Aerosol Code Comparisons With Releases From ACE MCCI Tests

Results of aerosol release calculations by six groups from six countries are compared with the releases from ACE MCCI Test L6. The codes used for these calculations included: SOLGASMIX-PV, SOLGASMIX Reactor 1986, CORCON.UW, VANESA 1.01, and CORCON mod2.04/VANESA 1.01. Calculations were performed with the standard VANESA 1.01 code and with modifications to the VANESA code such as the inclusion of various zirconium-silica chemical reactions. Comparisons of results from these calculations were made with Test L6 release fractions for U, Zr, Si, the fission-product elements Te, Ba, Sr, Ce, La, Mo and control materials Ag, In, and Ru. Reasonable agreement was obtained between calculations and Test L6 results for the volatile elements Ag, In and Te. Calculated releases of the low volatility fission products ranged from within an order of magnitude to five orders of magnitude of Test L6 values. Releases were over and underestimated by calculations. Poorest agreements were obtained for Mo and Si

Results of aerosol code comparisons with releases from ACE MCCI tests

Results of aerosol release calculations by six groups from six countries are compared with the releases from ACE MCCI Test L6. The codes used for these calculations included: SOLGASMIX-PV, SOLGASMIX Reactor 1986, CORCON.UW, VANESA 1.01, and CORCON mod2.04/VANESA 1.01. Calculations were performed with the standard VANESA 1.01 code and with modifications to the VANESA code such as the inclusion of various zirconium-silica chemical reactions. Comparisons of results from these calculations were made with Test L6 release fractions for U, Zr, Si, the fission-product elements Te, Ba, Sr, Ce, La, Mo and control materials Ag, In, and Ru. Reasonable agreement was obtained between calculations and Test L6 results for the volatile elements Ag, In and Te. Calculated releases of the low volatility fission products ranged from within an order of magnitude to five orders of magnitude of Test L6 values. Releases were over and underestimated by calculations. Poorest agreements were obtained for Mo and Si

Relapse or reinfection of hepatitis C after direct acting antiviral treatment: unraveled by phylogenetic analysis. Results from the Spanish GEHEP-004 cohort

Background: Despite high response rates associated to DAA treatment, no protective immunity is acquired, so patients that are cured after treatment can be infected with a new HCV strain, and therefore may be responsible for further transmission. Consequently, viral eradication may be hampered by high reinfection and transmission rates among patients with persistent risk behaviour. Distinguishing between virological relapse and reinfection is crucial to determine the true efficacy of current therapies and to define the most appropriate retreatment if needed. Methods: The GEHEP-004 cohort includes approximately 300 patients failing to different DAA regimens from 42 Spanish centers. For 53 patients treated between 2014 and 2016, the virus was sampled at two time points, before start of therapy and at time of failure. Sequencing was performed for two or three regions (NS3 – NS5A – NS5B), depending on the DAA regimen administered. For each taxon, the ten most similar sequences were retrieved from public databases by the use of BLAST. Concatenated alignments were used to infer phylogenetic trees by neighbour-joining and maximum-likelihood algorithms, with the GTR gamma model and 1000 bootstrap replicates. When comparing strains before and after treatment in one patient, evidence of reinfection was defined as a difference in HCV genotype or subtype, or as a significantly different clustering in distant clades in the tree. Evidence of relapse was defined as significant clustering in the same clade, while no conclusion was drawn when clades were supported with a bootstrap <70%. Simplot was used to detect recombination. Results: Genotype assignment by phylogenetic analysis revealed nine discordant cases (17.0%) with commercial assays at genotype and subtype level, while no recombinants were identified. At baseline, 41.5% of patients were determined to be infected with HCV1a, followed by HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%). Overall, 60.4% was co-infected with HIV. The large majority of patients for which the transmission route of infection was known, was classified as people who inject drugs (PWID) (78.6%), often co-infected with HIV (27/33) and half of them infected with HCV1a. Sexual transmission was observed in seven cases, of which five in HIV-positive men who have sex with men (MSM). Due to poor phylogenetic signal of single fragments, conclusions were only drawn for concatenated alignments. Overall, five patients were reinfected with a different HCV strain (4 PWID + 1 MSM), of which three with a different HCV genotype or subtype, and four co-infected with HIV. Virological relapse was defined for 44 patients, while no conclusion could be drawn for four patients. Conclusions: In our cohort, the majority of patients experienced a virological relapse. Almost 10% were reinfected, most of them PWID and HIV co-infected. Since about half of those reinfected, showed the same subtype as at baseline, phylogenetics is needed, not only to determine the correct HCV genotype, but also to distinguish between relapse and reinfection. Of note, phylogenetic analysis can only result in confident conclusions when long genomic stretches with sufficient phylogenetic signal are available, stressing the need to perform full-genome sequencing or to concatenate multiple regions.status: accepte

Size-Dependent Phase Transformations in Bismuth Oxide Nanoparticles. I. Synthesis and Evaporation

At the nanoscale material properties can be tuned by altering the size and shape of the specimen. Such effects are quite well investigated for metallic materials. On the other hand inorganic compounds have received relatively little interest due to the more demanding experimental procedures. While the size effects are similar for any kind of inorganic material, the degree of size-dependent changes depends on the bond strength and bond nature of the material at the surface: the higher the surface energy, the stronger the size dependence

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