Long-term effectiveness and tolerability of dolutegravir/lamivudine in treatment-naive people with HIV: an analysis of a multicentre cohort at 96 weeks.

Objectives: To evaluate the long-term effectiveness, persistence and tolerability of dolutegravir (DTG)/lamivudine (3TC), compared with the most frequently prescribed first-line treatment regimens, among antiretroviral-naive people with HIV from CoRIS, a multicentre cohort in Spain, in 2018-23.

Methods: We used multivariable regression models to compare viral suppression (VS) (HIV RNA viral load <50 copies/mL), change in CD4 cell counts, persistence and treatment discontinuations due to adverse events (AEs), at 96 (±24) weeks after treatment initiation.

Results: Of 2359 participants, DTG/3TC was prescribed in 472 (20.

Orthopalladated imidazolones and thiazolones: synthesis, photophysical properties and photochemical reactivity.

The reaction of Pd(OAc) with ()-5-arylidene-4-(4)-imidazolones (2a-e) and ()-4-arylidene-5(4)-thiazolones (3a-e) in trifluoroacetic acid results in the corresponding orthopalladated dinuclear complexes (4a-e, imidazolones; 11a-d, thiazolones) with trifluoroacetate bridges through regioselective C-H activation at the position of the 4-arylidene group. Compound 4e, which contains an imidazolone substituted at 2- and 4-positions of the arylidene ring with methoxide groups and exhibits strong push-pull charge transfer, is an excellent precursor for the synthesis of fluorescent complexes with green yellowish emission and remarkable quantum yields. Breaking the bridging system with pyridine yields the mononuclear complex 5e ( = 5%), while metathesis of trifluoroacetate ligands with chloride leads to the dinuclear complex 6e, also a precursor of fluorescent complexes by breaking the chloride bridging system with pyridine (7e, = 7%), or by substitution of chloride ligands with pyridine (8e, = 15%) or acetylacetonate (9e, = 2%).

Cardiovascular events in delayed presentation of HIV: the prospective PISCIS cohort study.

Objectives: People with HIV (PWH) have a higher cardiovascular risk than the general population. It remains unclear, however, whether the risk of cardiovascular disease (CVD) is higher in late HIV presenters (LP; CD4 ≤ 350 cells/μL at HIV diagnosis) compared to PWH diagnosed early. We aimed to assess the rates of incident cardiovascular events (CVEs) following ART initiation among LP compared to non-LP.

Fluorescence Amplification of Unsaturated Oxazolones Using Palladium: Photophysical and Computational Studies.

Weakly fluorescent ()-4-arylidene-5-(4)-oxazolones (), Φ < 0.1%, containing a variety of conjugated aromatic fragments and/or charged arylidene moieties, have been orthopalladated by reaction with Pd(OAc). The resulting dinuclear complexes () have the oxazolone ligands bonded as a C^N-chelate, restricting intramolecular motions involving the oxazolone.

Synthesis of Bis(amino acids) Containing the Styryl-cyclobutane Core by Photosensitized [2+2]-Cross-cycloaddition of Allylidene-5(4)-oxazolones.

The irradiation of 2-aryl-4-(-3'-aryl-allylidene)-5(4)-oxazolones with blue light (456 nm) in the presence of [Ru(bpy)](BF) (bpy = 2,2'-bipyridine, 5% mol) gives the unstable cyclobutane-bis(oxazolones) by [2+2]-photocycloaddition of two oxazolones . Each oxazolone contributes to the formation of with a different C=C bond, one of them reacting through the exocyclic C=C bond, while the other does so through the styryl group. Treatment of unstable cyclobutanes with NaOMe/MeOH produces the oxazolone ring opening reaction, affording stable styryl-cyclobutane bis(amino acids) .

Luminescence and Palladium: The Odd Couple.

The synthesis, photophysical properties, and applications of highly fluorescent and phosphorescent palladium complexes are reviewed, covering the period 2018-2022. Despite the fact that the Pd atom appears closely related with an efficient quenching of the fluorescence of different molecules, different synthetic strategies have been recently optimized to achieve the preservation and even the amplification of the luminescent properties of several fluorophores after Pd incorporation. Beyond classical methodologies such as orthopalladation or the use of highly emissive ligands as porphyrins and related systems (for instance, biladiene), new concepts such as AIE (Aggregation Induced Emission) in metallacages or in coordination-driven supramolecular compounds (CDS) by restriction of intramolecular motions (RIM), or complexes showing TADF (Thermally Activated Delayed Fluorescence), are here described and analysed.

Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens.

Objectives: To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings.

Methods: This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020.

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers.

The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old.

Reactivity of ()-4-Aryliden-5(4)-thiazolones: [2 + 2]-Photocycloaddition, Ring-Opening Reactions, and Influence of the Lewis Acid BF.

The irradiation of ()-2-phenyl-4-aryliden-5(4)-thiazolones with blue light (465 nm) in CHCl solution promotes [2 + 2]-photocycloaddition of the exocyclic C═C bonds and the formation of the dispirocyclobutanes . This reaction takes place with high stereoselectivity, given that the ε-isomer (1,3 head-to-tail syn coupling) is formed in more than 90% yield in most of the cases. However, irradiation of 5(4)-thiazolones with blue light (456 nm) in dry MeOH in the presence of BF·OEt leads to the monospirocyclobutanes with full stereoselectivity, also affording the ε-isomer.

Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.

Epigenome-wide association study of COVID-19 severity with respiratory failure.

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities.

Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.

Fluorescent Orthopalladated Complexes of 4-Aryliden-5(4)-oxazolones from the Kaede Protein: Synthesis and Characterization.

The goal of the work reported here was to amplify the fluorescent properties of 4-aryliden-5(4)-oxazolones by suppression of the hula-twist non-radiative deactivation pathway. This aim was achieved by simultaneous bonding of a Pd center to the N atom of the heterocycle and the carbon of the arylidene ring. Two different 4-(()-arylidene)-2-(()-styryl)-5(4)-oxazolones, the structures of which are closely related to the chromophore of the Kaede protein and substituted at the 2- and 4-positions of the arylidene ring ( OMe; F), were used as starting materials.

HIV-associated neurocognitive impairment in stable people living with HIV on ART in rural Tanzania.

Objectives: Few studies have assessed cognitive impairment among healthy people living with HIV (PLWH) who are stable on antiretroviral treatment (ART) in sub-Saharan Africa.

Methods: We conducted a cross-sectional study among a random sample of stable adult PLWH from rural Tanzania on ART for more than 1 year and without immunological failure or pre-existing neurological disease. We evaluated the prevalence and risk factors for neurocognitive impairment (NCI), assessed through neuropsychological tests, functional and depression questionnaires and defined as a mean Z-score ≤ -1 in two or more cognitive domains.

Effectiveness and safety of first-line antiretroviral regimens in clinical practice: a multicentre cohort study.

Objectives: We compared 48 week effectiveness and safety of first-line antiretroviral regimens.

Methods: We analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting the most commonly used antiretroviral regimens from 2014 to 2018. We used multivariable regression models to assess the impact of initial regimen on: (i) viral suppression (VS) (viral load <50 copies/mL); (ii) change in CD4 cell count; (iii) CD4/CD8 normalization (>0.

Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression.

Objective: We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts.

Methods: A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count <200 cells/μL and successful viral control for two years. CD4 count increase below 200 cells/μL after two years on cART was used to define INR (immunological non-responder) patients.

Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice.

Background: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART.

Objectives: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain.

Methods: During the period 2012-17, 1109 patients from CoRIS were analysed.

HIV pre-exposure prophylaxis (PrEP) in Spain: political and administrative situation.

This study focuses on actions at the political and administrative level in Spain in relation to the implementation of pre-exposure prophylaxis (PrEP). We analysed a whole range of different formal initiatives taken by the political and administrative actors involved. The information was obtained from official public data sources.

Increased frequencies of Th17 cells and IL17a-producing regulatory T-cells preceding the immunodiscordant response to antiretroviral treatment.

Background: Despite the fact that antiretroviral therapy (cART) suppresses HIV-viremia, an adequate CD4 T-cell recovery is not always achieved (immunodiscordant response to cART). IL17a-producing CD4 T-cells (Th17) constitutes an important subset involved in the preservation of mucosal surfaces integrity, which depletion has been associated with disease progression in HIV-infection. However, whether Th17 frequency at cART initiation is associated with a poor CD4 T-cell recovery has not been yet explored.

Combined effect of sex and age in response to antiretroviral therapy in HIV-infected patients.

Background: Gender-specific data on the management of HIV infection are scarce. Further, an increase in the proportion of new HIV diagnoses in older persons has been observed. Using data from the CoRIS cohort, we compared immunovirological responses and survival in HIV-infected men and women who started their first combination antiretroviral therapy (cART) when aged < /≥50 years.

Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

Background: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/μL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression.

Clinical outcomes of patients infected with HIV through use of injected drugs compared to patients infected through sexual transmission: late presentation, delayed anti-retroviral treatment and higher mortality.

Aims: To compare patients who acquired HIV infection through use of injected drugs (HIV-IDU) with patients who acquired HIV by sexual transmission (HIV-ST) in terms of late presentation (LP), delay in anti-retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS.

Design: Prospective multi-centre cohort study of HIV-infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS).

Setting: Thirty-one centres from the Spanish public health-care system.