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Coupled Cluster Benchmarking of Large Noncovalent Complexes in L7 and S12L as Well as the C

In this work, we report the benchmark binding energies of the seven complexes within the L7 data set, six host-guest complexes from the S12L data set, a C

Trends and projections in sexually transmitted infections in people aged 45 years and older in England analysis of national surveillance data.

We describe the epidemiology of sexually transmitted infections (STIs) and HIV in people aged ⩾45 years in England and provide future projections about the burden of STIs in this age group. Analysis of national surveillance data in England from 2014 to 2019 for chlamydia, gonorrhoea, herpes, syphilis, anogenital warts and HIV was carried out. Time trends were assessed by the Poisson regression and reported using incidence rate ratios (IRRs). Two scenarios were modelled to predict the number of new STI diagnoses and associated costs in 2040. In 2019, there were 37,692 new STI diagnoses in people ⩾45 years in England. Between 2014 and 2019, there was a significant increase in the rate of new STI diagnoses in men (IRR 1.05, STI rates in England are increasing in people aged ⩾45 years. The population is ageing and older people will contribute an increasing burden to STI costs if this trend continues. The reasons for this trend are not fully understood and further longitudinal epidemiological research is needed. Sexual health promotion campaigns and healthcare interventions targeted at older people should be prioritised.

Inhibitors of HIV-1 Nef applications and developments for a practical cure.

Antiretroviral therapy can control human immunodeficiency virus type 1 (HIV-1) replication in people living with HIV however, these treatments are not curative and no practical approach for an HIV-1 cure has yet shown success in clinical trials. Counteracting the multiple barriers HIV-1 presents against a practical cure is a direct means to functionalize these curative approaches in vivo. Pharmacological inhibition of the HIV-1 accessory protein, Nef, represents a particularly promising and ambitious approach, with Nef inhibitors holding the potential to reverse HIV-1-related defects in T cell receptor and kinase signaling, apoptosis, autophagy and most importantly, antigen presentation. Together, the capacity for Nef inhibitors to restore these activities underscores their potential as supportive agents in a practical HIV-1 cure. In this review, we outline a rationale for pharmacologically targeting Nef and review the progress made in the identification and development of Nef inhibitors.

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Résumé La thérapie anti-rétrovirale peut contrôler la réplication du virus de limmunodéficience humaine de type 1 (VIH-1) chez les individus vivant avec le VIH. Par contre, ces traitements ne constituent pas une guérison et aucune approche pour une guérison du VIH-1 na encore montré de succès lors des études cliniques. Les approches de guérison sont souvent contrées in vivo par des barrières développées par le VIH-1. Linhibition pharmacologique de la protéine accessoire Nef du VIH-1 représente une approche ambitieuse et prometteuse pour développer une nouvelle stratégie de guérison. Des petites molécules inhibitrices de Nef peuvent inverser les défauts reliés à linfection par le VIH dans la signalisation des récepteurs des cellules T et les kinases, lapoptose, lautophagie et surtout, la présentation dantigène. Ensemble, ces activités démontrent la grande capacité des inhibiteurs de Nef à être appliqués comme agents thérapeutiques dans un traitement contre le VIH-1. Dans cette revue, nous présentons les motifs pour lesquels Nef constitue une cible thérapeutique et nous soulignons les progrès effectués dans lidentification et le développement dinhibiteurs de Nef.

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Résumé La latence du virus de limmunodéficience humaine (VIH) est actuellement un obstacle majeur à léradication des cellules infectées. En effet, en état de latence, le VIH se réplique peu et produit une faible quantité de protéines virales il est donc hors datteinte des traitements antirétroviraux ciblant les enzymes essentielles du cycle viral et invisible pour le système immunitaire qui ne peut détecter les protéines virales à la surface des cellules infectées. De plus, la latence étant un état réversible maintenu principalement par la pression exercée par les traitements antirétroviraux sur le virus qui peut se réactiver lorsque ces traitements sont interrompus. En conséquence, les personnes infectées par le VIH sont contraintes de prendre les traitements antirétroviraux à vie. Pour ces raisons, des molécules actuellement à létude ciblent la latence, notamment à laide dune stratégie dite de blocage et verrouillage (block and lock) qui aspire à maintenir le VIH dans un état de latence profonde. Le développement de telles molécules requiert une connaissance approfondie des mécanismes régissant la transcription des gènes du VIH. Dans cette revue, nous décrirons les mécanismes permettant la transcription des gènes viraux ainsi que les molécules associées à la stratégie de blocage et verrouillage.

Contribution of Natural Killer cells to HIV control in Elite Controllers.

Untreated HIV infection usually leads to disease progression and development of the acquired immunodeficiency syndrome. A rare subset of people living with HIV control HIV without anti-retroviral therapy. These individuals, known as Elite Controllers (ECs), represent examples of a functional HIV cure. ECs differ from non-controllers is many aspects. Some are infected with defective virus, most have potent CD4 and CD8 virus-specific T cell responses and proviruses in these individuals tend to be inserted into regions with characteristics of deep latency. Natural Killer (NK) cells are innate immune cells that function at the intersection of innate and adaptive immunity. They have the capacity to recognize and respond to HIV-infected cells from the earliest stages in infection. NK cells can be activated through antibody independent and antibody dependent mechanisms to elicit functions that control HIV and kill infected cells. This manuscript will review the role of NK cells in HIV control.

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Résumé En labsence de traitement antirétroviral, linfection par le VIH progresse normalement vers le syndrome dimmunodéficience acquise. Une minorité de sujets infectés par le VIH sont toutefois capables de contrôler la réplication virale en labsence de traitement. Ces patients appelés sujets contrôleurs délite (EC pour elite controllers) représentent un exemple de guérison fonctionnelle de linfection par le VIH. Certains EC sont infectés par des virus défectifs, alors que dautres ont des provirus intégrés dans des zones non transcrites de la chromatine. Cependant, la plupart des EC se distinguent des sujets non-contrôleurs parce quils développent de fortes réponses T CD4 et CD8 spécifiques au VIH. Les cellules tueuses naturelles (NK pour Natural Killer) sont des cellules du système immunitaire inné qui fonctionnent à linterface entre limmunité innée et limmunité acquise. Les cellules NK sont capables de reconnaître et de répondre à des cellules infectées dès les stades précoces de linfection. Les cellules NK peuvent être activées de fac¸on indépendante et dépendante des anticorps afin dexercer des fonctions antivirales et éliminer les cellules infectées. Ce manuscrit discutera du rôle des cellules NK dans le contrôle de linfection par le VIH.

Immunological mechanisms involved in the persistence of HIV reservoirs.

Antiretroviral therapy (ART) controls viral replication and has dramatically improved the quality and life expectancy of people living with HIV (PLHIV). However, almost 40 years after the discovery of HIV, there is still no cure even after years of effective ART, the virus persists in cells, primarily memory CD4 T cells. These cells are a perennial source of infectious viruses, which necessitate that people living with HIV continue ART for life. Research on HIV reservoirs over the past 25 years has provided insight into how some infected cells persist for decades without being cleared by ART nor by immune responses. HIV hides in cells with extended lifespans, which have the capacity to proliferate through diverse mechanisms and which preferentially express several receptors that allow them to remain invisible to the immune system. A better understanding of these mechanisms of persistence is a necessary prerequisite for the development of therapeutic strategies aimed at eradicating HIV.

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Résumé Les thérapies antirétrovirales (TAR) permettent de contrôler la réplication virale et ont considérablement amélioré la qualité et lespérance de vie des personnes vivant avec le VIH (PVVIH). Toutefois, près de 40 ans après la découverte du virus, il nexiste toujours pas de traitement curatif permettant déliminer le VIH de lorganisme Même après des années de TAR efficace, le virus persiste dans des cellules, principalement des lymphocytes T CD4 mémoires, qui constituent une source pérenne de virus infectieux et qui nécessitent de poursuivre les traitements à vie. Les recherches sur les réservoirs du VIH menées au cours des 25 dernières années ont permis de mieux comprendre comment certaines cellules infectées persistent pendant des décennies sans être éliminées, ni par les TAR, ni par les réponses immunitaires. Le VIH « se cache » dans des cellules à durée de vie très longue, qui ont la capacité de proliférer par différents mécanismes et qui expriment préférentiellement certains récepteurs leur permettant de demeurer invisibles au système immunitaire. Une meilleure compréhension de ces mécanismes de persistance est un prérequis nécessaire à la mise au point de stratégies thérapeutiques visant à éradiquer le VIH.

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Résumé La thérapie antirétrovirale (TAR) inhibe la réplication du VIH-1 mais nest pas curative. Pendant la TAR, le génome intégré du VIH-1 persiste principalement dans les lymphocytes T mémoires CD4 ainsi que dans dautres cellules immunitaires, notamment les cellules myéloïdes comme les macrophages. La majorité de ces cellules ne produisent pas de particules virales infectieuses et constituent le réservoir latent. Dimportants progrès ont été réalisés dans lidentification des facteurs qui contribuent à létablissement et au maintien du réservoir latent qui demeure le principal obstacle à léradication du VIH-1. Dans cette revue, nous mettrons en relief le rôle des microARN dans le développement des réservoirs viraux vu que ceux-ci sont dimportants modulateurs de lexpression génique, ciblant des facteurs de transcription ainsi que dautres effecteurs nécessaires à linfection productive du VIH-1. Certains microARN ciblent même directement les transcrits viraux. Nous soulignerons les grandes questions en suspens sur la participation active des microARN de lhôte aux mécanismes de persistance virale et notamment ceux régissant la latence virale. Finalement, compte tenu des stratégies actuelles qui ne permettent toujours pas de réduire efficacement les réservoirs viraux, les perspectives quant à lutilisation des microARN comme approche pour contrer la persistance des réservoirs latents seront discutées.

Age group differences in substance use, social support, and physical and mental health concerns among people living with HIV two years after receiving primary care-based alcohol treatment.

Serial surveys of Hong Kong medical students regarding attitudes towards HIVAIDS from 2007 to 2017.

With widespread adoption of antiretroviral therapy, human immunodeficiency virus (HIV) epidemiology has changed since the late 2000s. Accordingly, attitudes towards the disease may also have changed. Because medical students are future physicians, their attitudes have important implications in access to care among patients with HIVacquired immunodeficiency syndrome (AIDS). Here, we performed a survey to compare medical students attitudes towards HIVAIDS between the late 2000s (2007-2010) and middle 2010s (2014- 2017). From 2007 to 2010, we surveyed three cohorts of medical students at the end of clinical training to assess their attitudes towards HIVAIDS. From 2014 to 2017, we surveyed three additional cohorts of medical students at the end of clinical training to compare changes in attitudes towards HIVAIDS between the late 2000s and middle 2010s. Each set of three cohorts was grouped together to maximise sample size comparisons were performed between the 2007-2010 and 2014-2017 cohorts. From 2007 to 2010, 546 medical students were surveyed from 2014 to 2017, 504 students were surveyed. Compared with students in the late 2000s, significantly fewer students in the mid-2010s initially encountered patients with HIV during attachment to an HIV clinic or preferred to avoid work in a field involving HIVAIDS significantly more students planned to specialise in HIV medicine. Student willingness to provide HIV care remained similar over time approximately 78% of students were willing to provide care in each grouped cohort. Although medical students had more positive attitudes towards HIVAIDS, their willingness to provide HIV care did not change between the late 2000s and middle 2010s.

Comparison of temporal evolution of computed tomography imaging features in COVID-19 and influenza infections in a multicenter cohort study.

To compare temporal evolution of imaging features of coronavirus disease 2019 (COVID-19) and influenza in computed tomography and evaluate their predictive value for distinction. In this retrospective, multicenter study 179 CT examinations of 52 COVID-19 and 44 influenza critically ill patients were included. Lung involvement, main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings were evaluated by two independent observers. Additional findings and clinical data were compared patient-wise. A decision tree analysis was performed to identify imaging features with predictive value in distinguishing both entities. In contrast to influenza patients, lung involvement remains high in COVID-19 patients > 14 days after the diagnosis. The predominant pattern in COVID-19 evolves from ground glass at the beginning to consolidation in later disease. In influenza there is more consolidation at the beginning and overall less ground glass opacity (p 0.002). Decision tree analysis yielded the following Earlier in disease course, pleural effusion is a typical feature of influenza (p 0.007) whereas ground glass opacities indicate COVID-19 (p 0.04). In later disease, particularly more lung involvement (p < 0.001), but also less pleural (p 0.005) and pericardial (p 0.003) effusion favor COVID-19 over influenza. Regardless of time point, less lung involvement (p < 0.001), tree-in-bud (p 0.002) and pericardial effusion (p 0.01) make influenza more likely than COVID-19. This study identified differences in temporal evolution of imaging features between COVID-19 and influenza. These findings may help to distinguish both diseases in critically ill patients when laboratory findings are delayed or inconclusive.

Control and Anticontrol of chaos in Fractional-order models of Diabetes, HIV, Dengue, Migraine, Parkinsons and Ebola Virus diseases.

This work proposes new fractional-order (FO) models of six chaotic diseases whose fractional dynamics have not been studied so far in literature. Secondly, design and analysis of suitable controllers to control chaos where present, and that of anticontrollers to generate chaos where absent, for these newly proposed FO models of diseases, are put forward. The proposed controllers and anticontrollers address the problem of the health hazards arising from the dysfunctionalities due to the impact of chaos in these biological models. Controllers to supress chaos in four diseases, namely, FO Diabetes Mellitus, FO Human Immunodeficiency Virus (HIV), FO Ebola Virus and FO Dengue models are designed by Back-stepping, Adaptive Feedback and Sliding Mode Control strategies, whereas anticontrollers to introduce chaos in diseases, namely, FO Parkinsons illness and FO Migraine models, are carried out by Linear State Feedback, Single State Sinusoidal Feedback and Sliding Mode Anticontrol strategies. The equilibrium points, eigenvalues and Lyapunov Exponents of the FO disease models are evaluated and indicate the significance of chaos in them and necessitate upon the requirement of controllers and anticontrollers accordingly. The simulation results in terms of bifurcation diagrams, time series plots and phase portraits confirm the successful accomplishment of the control objectives.

Safety and Adverse Events Related to COVID-19 mRNA Vaccines a Systematic Review.

Knowledge of vaccine-related adverse events is crucial as they are among the most ‎important factors ‎that cause hesitation in receiving vaccines. Therefore, we aimed to systematically ‎review the adverse events ‎related to the mRNA vaccines reported in the literature.‎. A systematic literature search was carried out in the databases of Scopus, PubMed, ‎Cochrane, and Web ‎of Science. We selected original studies that explored the side effects of ‎mRNA ‎COVID-19 vaccines using a two-phase (titleabstract and full-text) screening process.‎. Cardiac ‎complications were the most commonly reported severe adverse events. It appeared that ‎systemic adverse reactions are more ‎common after the second dose of vaccines. The number of ‎adverse effects reported after the Pfizer vaccine was ‎higher than other vaccines, mostly due to its ‎earlier approval and more widespread use throughout the world. Cardiac adverse events had a ‎‎higher prevalence but no significant association has been found between COVID-19 mRNA vaccines ‎and cardiac ‎adverse events except for myopericarditis. ‎. Vaccines ‎play a crucial role in controlling the COVID-19 pandemic and decreasing ‎mortalities and the results of the present ‎review acknowledge the fact that the benefits outweigh the ‎adverse events of these vaccines.‎.

Severe acute respiratory syndrome coronavirus 2 variants-Possibility of universal vaccine design A review.

Both novel and conventional vaccination strategies have been implemented worldwide since the onset of coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite various medical advances in the treatment and prevention of the spread of this contagious disease, it remains a major public health threat with a high mortality rate. As several lethal SARS-CoV-2 variants continue to emerge, the development of several vaccines and medicines, each with certain advantages and disadvantages, is underway. Additionally, many modalities are at various stages of research and development or clinical trials. Here, we summarize emerging SARS-CoV-2 variants, including delta, omicron, and stealth omicron, as well as available oral drugs for COVID-19. We also discuss possible antigen candidates other than the receptor-binding domain protein for the development of a universal COVID-19 vaccine. The present review will serve as a helpful resource for future vaccine and drug development to combat COVID-19.

Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents Molecular Modeling, Synthesis and Biological Evaluation.

HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the worlds most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes. The synthesized malonic acid analogs were evaluated for their activities against the HIV virus (NL4-3) in HeLa cells cultures. Among them, compound 3 was the most potent anti-HIV agent with 55.20% inhibition at 10 μM and an EC50 of 8.4 μM. Interestingly, all the synthesized compounds do not show significant cytotoxicity at a concentration of 10 μM. As a result, these compounds may serve as worthy hits for the development of novel anti-HIV-agents.

Uracil derivatives as HIV-1 capsid protein inhibitors design,

A series of novel uracil derivatives such as bispyrimidine dione and tetrapyrimidine dione derivatives were designed based on the existing four-point pharmacophore model as effective HIV capsid protein inhibitors. The compounds were initially docked with an HIV capsid protein monomer to rationalize the ideas of design and to find the potential binding modes. The successful design and computational studies led to the synthesis of bispyrimidine dione and tetrapyrimidine dione derivatives from uracil and aromatic aldehydes in the presence of HCl using novel methodology. The

Evaluation of serological assays for SARS-CoV-2 antibody testing from dried blood spots collected from cohorts with prior SARS-CoV-2 infection.

Dried blood spot (DBS) specimens are a useful serosurveillance tool particularly in hard-to-reach populations but their application for detecting SARS-CoV-2 infection is poorly characterised. To compare detection of naturally acquired SARS-CoV-2 antibodies in paired DBS and serum specimens using commercially available serological immunoassays. Specimens were collected through St Vincents Hospital observational post COVID-19 cohort study (ADAPT). Laboratory spotted DBS from venepuncture were initially tested on seven assays, a DBS validation completed on three with clinically collected fingerstick DBSs tested on one. Sensitivity for Euroimmun nucleocapsid (NCP) IgG ELISA from laboratory spotted DBS (n145), Euroimmun spike, IgG ELISA from laboratory spotted DBS (n161), and Binding Site total antibody ELISA from clinically collected fingerstick DBS (n391) was 100% (95% CI 95.8-100%), 100% (95% CI 95.8-100%) and 92.9% (95% CI 89.5-95.5%), respectively. Specificity was 66.2% (95% CI 53.6-77.0%), 96% (95% CI 88.7-99.1%) and 98.8% (95% CI 93.3-99.9%), respectively. All three assays results displayed a strong positive correlation between DBS compared to paired serum. The Binding Site™ spike total antibody and Euroimmun™ spike IgG ELISAs provided good analytical performance, demonstrating that DBS specimens could facilitate specimen collection in the epidemiological surveillance of SARS-CoV-2 infection. This is highly applicable in populations and settings where venepuncture is problematic (including community based regionalremote settings, nursing homes, prisons, and schools).

BAGEL A BAYESIAN GRAPHICAL MODEL FOR INFERRING DRUG EFFECT LONGITUDINALLY ON DEPRESSION IN PEOPLE WITH HIV.

Access and adherence to antiretroviral therapy (ART) has transformed the face of HIV infection from a fatal to a chronic disease. However, ART is also known for its side effects. Studies have reported that ART is associated with depressive symptomatology. Large-scale HIV clinical databases with individuals longitudinal depression records, ART medications, and clinical characteristics offer researchers unprecedented opportunities to study the effects of ART drugs on depression over time. We develop BAGEL, a Bayesian graphical model to investigate longitudinal effects of ART drugs on a range of depressive symptoms while adjusting for participants demographic, behavior, and clinical characteristics, and taking into account the heterogeneous population through a Bayesian nonparametric prior. We evaluate BAGEL through simulation studies. Application to a dataset from the Womens Interagency HIV Study yields interpretable and clinically useful results. BAGEL not only can improve our understanding of ART drugs effects on disparate depression symptoms, but also has clinical utility in guiding informed and effective treatment selection to facilitate precision medicine in HIV.

Social identity support, descriptive norms, and economic instability in PrEP engagement for emerging adult MSM in the United States.

Rates of pre-exposure prophylaxis (PrEP) uptake for HIV prevention continue to increase rapidly among men who have sex with men (MSM) in the United States (U.S.) however, these increases have been slower among young MSM. Emerging adulthood (ages 18-25) is a time of transitions and social development, resulting in increased vulnerability to HIV. Analyzing data from a cross-sectional survey of emerging adult MSM (ages 18-25 years

Positive Health Check intervention tool usage during a feasibility pilot in HIV primary care clinics.

Positive Health Check (PHC), an interactive, web-based intervention, provides tailored behavioral health messages to support people with HIV in their HIV care. Users interact with a virtual doctor and based on responses to tailoring questions, PHC delivers relevant content modules addressing treatment initiation, medication adherence, retention in care, sexual risk reduction, mother-to-child transmission, and injection drug use. During a one-month feasibility pilot of PHC, patients in four HIV primary care clinics were invited to use PHC and tool usage metrics were collected and assessed. Descriptive analyses were conducted to characterize how the tool was used based on behavioral risk scenarios presented.Ninety-seven patients accessed PHC as part of the pilot, with 68 (70.1%) completing the intervention on average in 15 min. Out of 85 patients who viewed behavioral tips and commitments, 66 (77.7%) selected at least one tip to practice and 41 (48.2%) made at least one commitment to ask their provider a question. Patients spent the most time with adherence and sexual risk reduction content. The high level of tool engagement suggests that PHC was acceptable to patients regardless of length of time since diagnosis. PHC can be completed within a single visit and is a promising tool for PWH.

Predictors of treatment interruption among patients on antiretroviral therapy in Akwa Ibom, Nigeria outcomes after 12 months.

Understanding the characteristics of people living with HIV who interrupt antiretroviral therapy (ART) is critical for designing client-centered services to ensure optimal outcomes. We assessed predictors of treatment interruption in 22 HIV clinics in Nigeria. We reviewed records of HIV-positive patients aged ≥15 years who started ART 1 January and 31 March 2019. We determined treatment status over 12 months as either active, or interrupted treatment (defined as interruption in treatment up to 28 days or longer). Potential predictors were assessed using Cox hazard regression models. Overall, 1185 patients were enrolled on ART, 829 (70%) were female, and median age was 32 years

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo.

The capsid (CA) subunit of the HIV-1 Gag polyprotein is involved in several steps of the viral cycle, from the assembly of new viral particles to the protection of the viral genome until it enters into the nucleus of newly infected cells. As such, it represents an interesting therapeutic target to tackle HIV infection. In this study, we screened hundreds of compounds with a low cost of synthesis for their ability to interfere with Gag assembly in vitro. Representatives of the most promising families of compounds were then tested for their ability to inhibit HIV-1 replication in cellulo. From these molecules, a hit compound from the benzimidazole family with high metabolic stability and low toxicity, 2-(4-N,N-dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole (696), appeared to block HIV-1 replication with an IC50 of 3 µM. Quantitative PCR experiments demonstrated that 696 does not block HIV-1 infection before the end of reverse transcription, and molecular docking confirmed that 696 is likely to bind at the interface between two monomers of CA and interfere with capsid oligomerization. Altogether, 696 represents a promising lead molecule for the development of a new series of HIV-1 inhibitors.

Determinants and reasons for switching anti-retroviral regimen among HIV-infected youth in a large township of South Africa (2002-2019).

There are limited data exploring antiretroviral therapy (ART) changes and time to change among South Africa young people living with HIVAIDS. We describe the time to first drug switch, which includes ART regimen change (three drug switch) and substitutions (single drug switch). We describe common reasons for ART switch among young people aged 10 to 24 years in South Africa. We conducted a retrospective cohort study at a primary health care clinic in Cape Town, South Africa, providing ART to HIV-infected adolescents and adults since 2002. Those aged 10 to 24 years at ART initiation, who accessed care clinic between September 2002 and April 2019. Data was retrieved from electronic information systems ART regimens, ART changes, dates for initiation or stop of each drugregimen, laboratory results (viral loads, haemoglobin, liver enzyme results, and creatinine to support the reason for ART switch. From written records, we abstracted reason for single drug switch or regimen change, as well as socio demographic and clinical data. We fitted cox regression models to determine factors associated with ART switch (Having a change in one or more drugs in ART combination) and the rate of occurrence. Of 2601 adolescents included, 605 (24.9%) adolescents switched ART over 5090.5 person years at risk (PYAR), a rate of 11.9 100PYAR. Median follow-up time was 4.4 (± 3.2) years. At multivariable analysis, the older age group was protective of the risk of ART switch adjusted Hazard Ratio aHR 0.78, 95% CI 0.62-0.98, transfer status transferred out 1.42 1.11-1.82. The hazard of ART switch increased with more severe HIV-disease at ART start, as observed by increasing WHO clinical stage or reduced CD4 count at baseline. The primary reasons for ART switch were side effects (20.0%), virological failure (17.9%) and formulation switch (27.8%). Others reasons included pregnancy, Hepatitis B, tuberculosis and psychosis. ART switches are frequent and occur at a consistent rate across 7.5 years from initiation. The main reasons for ART switch were virological failure and drug side effects.

Defective HIV-1 genomes and their potential impact on HIV pathogenesis.

Defective HIV-1 proviruses represent a population of viral genomes that are selected for by immune pressures, and clonally expanded to dominate the persistent HIV-1 proviral genome landscape. There are examples of RNA and protein expression from these compromised genomes which are generated by a variety of mechanisms. Despite the evidence that these proviruses are transcribed and translated, their role in HIV pathogenesis has not been fully explored. The potential for these genomes to participate in immune stimulation is particularly relevant considering the accumulation of cells harboring these defective proviruses over the course of antiretroviral therapy in people living with HIV. The expression of defective proviruses in different cells and tissues could drive innate sensing mechanisms and inflammation. They may also alter antiviral T cell responses and myeloid cell functions that directly contribute to HIV-1 associated chronic comorbidities. Understanding the impact of these defective proviruses needs to be considered as we advance cure strategies that focus on targeting the diverse population of HIV-1 proviral genomes.

Household food insecurity, sense of community belonging, and access to a regular medical doctor as mediators in the relationship between mood andor anxiety disorders and self-rated general health in Canada between 2011 and 2016 a serial cross-sectional analysis.

To assess whether (household) food insecurity, access to a regular medical doctor, and sense of community belonging mediate the relationship between mood andor anxiety disorders and self-rated general health. We used six annual cycles of the Canadian Community Health Survey, including Canadian adults aged 18-59 years, between 2011 and 2016. Mediation models, adjusted for key determinants of health, were based on a series of weighted logistic regression models. The Sobel products of coefficients approach was used to estimate the indirect effect, and bootstrapping to estimate uncertainty. The annual (weighted) prevalence of mood andor anxiety disorders increased from 11.3% (2011) to 13.2% (2016). Across the 6 years, 23.9-27.7% of individuals with mood andor anxiety disorders reported fairpoor self-rated health as compared with 4.9-6.5% of those without mood andor anxiety disorders (p<0.001). Similarly, the 7.2-8.9% of the population reporting fairpoor self-rated health were disproportionately represented among individuals reporting food insecurity (21.1-26.2%, p<0.001) and a weak sense of community belonging (10.0-12.2%, p<0.001). A significantly lower prevalence of poor self-rated health was observed among respondents reporting having access to a regular medical doctor in 2012, 2015, and 2016. In 2016, sense of community belonging and food insecurity significantly mediated the effect of mood andor anxiety disorders on self-rated general health. Access to a regular medical doctor did not mediate this relationship. Efficient policies that address food insecurity and sense of community belonging are needed to decrease the mental health burden and improve health satisfaction of Canadians. RéSUMé OBJECTIF Déterminer si l’insécurité alimentaire (du ménage), l’accès à un médecin traitant et le sentiment d’appartenance à la communauté modèrent le lien entre les troubles anxieux etou de l’humeur et la santé générale autoévaluée. MéTHODE Nous avons utilisé six cycles annuels (2011 à 2016) de l’Enquête sur la santé dans les collectivités canadiennes incluant des Canadiens adultes de 18 à 59 ans. Nos modèles de modération, ajustés selon les principaux déterminants de la santé, reposaient sur une série de modèles de régression logistique pondérés. Nous avons utilisé l’approche des produits des coefficients de Sobel pour estimer les effets indirects, et l’autoamorçage pour estimer l’incertitude. RéSULTATS La prévalence annuelle (pondérée) des troubles anxieux etou de l’humeur a augmenté, passant de 11,3 % en 2011 à 13,2 % en 2016. Sur la période de six ans, 23,9 à 27,7 % des personnes ayant des troubles anxieux etou de l’humeur ont déclaré avoir une santé moyennemauvaise, contre 4,9 à 6,5 % des personnes n’ayant pas de troubles anxieux etou de l’humeur (p < 0,001). De même, les 7,2 à 8,9 % de la population ayant déclaré avoir une santé moyennemauvaise étaient disproportionnellement représentés chez les personnes disant être en situation d’insécurité alimentaire (21,1-26,2 %, p < 0,001) et avoir un faible sentiment d’appartenance à la communauté (10,0-12,2 %, p < 0,001). Une prévalence significativement plus faible de mauvaise santé autoévaluée a été observée chez les répondants ayant dit avoir accès à un médecin traitant en 2012, 2015 et 2016. En 2016, le sentiment d’appartenance à la communauté et l’insécurité alimentaire modéraient de façon significative l’effet des troubles anxieux etou de l’humeur sur la santé générale autoévaluée. L’accès à un médecin traitant ne modérait pas ce lien. CONCLUSION Des politiques efficaces pour aborder l’insécurité alimentaire et le sentiment d’appartenance à la communauté sont nécessaires pour réduire le fardeau des troubles mentaux et améliorer la satisfaction des Canadiens face à leur santé.

High frequency of neutralizing antibodies to type I Interferon in HIV-1 patients hospitalized for COVID-19.

The presence of anti-IFN neutralizing antibodies (NAB) has been reported in critically ill COVID-19 patients. We found that 87.5% (78) of HIV-1 patients co-infected with SARS-CoV-2 had serum anti-IFN-I NAB against IFN-α subtypes, IFN-β andor IFN-ω. Anti-IFN-I NAB were also detected in oropharyngeal samples. Patients with NAB were males, and those with high serum anti-IFN-αω NAB titer had severe illness and exhibited reduction in the expression of IFN-stimulated genes. Thus, high titer of anti-IFN-αω NAB may contribute to the greater severity of COVID-19 in HIV-1 infected patients.

Correction Aerobic Exercise in HIV-Associated Neurocognitive Disorders Protocol for a Randomized Controlled Trial.

This corrects the article DOI 10.219629230..

Neighborhood Characteristics, Intersectional Discrimination, Mental Health, and HIV Outcomes Among Black Women Living With HIV, Southeastern United States, 2019‒2020.

Methods in HIV-Related Intersectional Stigma Research Core Elements and Opportunities.

Researchers are increasingly recognizing the importance of studying and addressing intersectional stigma within the field of HIV. Yet, researchers have, arguably, struggled to operationalize intersectional stigma. To ensure that future research and methodological innovation is guided by frameworks from which this area of inquiry has arisen, we propose a series of core elements for future HIV-related intersectional stigma research. These core elements include multidimensional, multilevel, multidirectional, and action-oriented methods that sharpen focus on, and aim to transform, interlocking and reinforcing systems of oppression. We further identify opportunities for advancing HIV-related intersectional stigma research, including reducing barriers to and strengthening investments in resources, building capacity to engage in research and implementation of interventions, and creating meaningful pathways for HIV-related intersectional stigma research to produce structural change. Ultimately, the expected payoff for incorporating these core elements is a body of HIV-related intersectional stigma research that is both better aligned with the transformative potential of intersectionality and better positioned to achieve the goals of Ending the HIV Epidemic in the United States and globally. (

StatPearls

Highly active antiretroviral therapy (HAART) is a medication regimen used to manage and treat human immunodeficiency virus type 1 (HIV-1). It is composed of several drugs in the antiretroviral classes of medications. This activity outlines the indications, mechanism of action, and contraindications for various HAART medications in the management of HIV. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to the interprofessional healthcare team members in the care of patients with HIV-1 and related conditions.

StatPearls

Bacillus Calmette-Guérin (BCG) is the live attenuated vaccine form of Mycobacterium bovis used to prevent tuberculosis and other mycobacterial infections. The vaccine was developed by Calmette and Guérin and was first administered to human beings in 1921. BCG is the only vaccine against tuberculosis. It is the most widely administered vaccine and usually a part of the routine newborn immunization schedule. BCG vaccine also offers protection against non-tuberculous mycobacterial infections like leprosy and Buruli ulcer. It is also used in the treatment of superficial carcinoma of the bladder. BCG vaccine is a fairly safe vaccine and it is not associated with severe complications. Prior to the mycobacterial infection, vaccine-induced or acquired naturally can protect against subsequent infection due to mycobacteria including tuberculosis. Prior infection with nontuberculous mycobacteria and

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Viral pneumonia is defined as a disease entity wherein there is the viral causation of oxygen and carbon dioxide gas exchange abnormalities at the level of the alveoli, secondary to viral-mediated andor immune response-mediated inflammation. The traditional role of viral pneumonia was as a disease found predominantly in the very young, the elderly, and those exposed to influenza. In the past, the diagnosis of viral pneumonia was predicated on it being somewhat a diagnosis of exclusion. History, physical exam, chest radiography, and available lab work (until recently) lacked sensitivity and specificity. Once bacterial pneumonia has been excluded, then viral pneumonia diagnosis was entertained. Traditionally, the treatment of viral pneumonia revolved around supportive care Supplemental oxygen when indicated. Airway augmentation as appropriate. Monitoring of and replacement of any fluid deficits. Symptomatic control of temperature and cough. Rest to reduce oxygen demand. Treatment of any comorbidities andor concomitant bacterial pneumonia. The concepts of diagnosis, prevalence, clinical role, and treatment of viral pneumonia are in flux for several reasons. 1. There is a growing population at increased risk of viral pneumonia The increases in life span and early infant survivability have created an additional population at greater risk of viral pneumonia. The increased number of those receiving immune-impairing therapy (radiation andor chemotherapy) for cancer. The increased use of disease-modifying hematologicalimmunological agents in chronic illness, resulting in secondary impaired immunity. The advent of HIV. The increase in the number of patients with inborn immune impairment serving bacterial infection secondary to antibiotic therapy. The increased incidence of organ transplantation and immunosuppressive therapy. 2. The availability of sensitive, specific, real-time-result-available testing for viral entities Polymerase chain reaction (PCR) technology is replacing viral cultures and serial viral antigen titers. Both viral culture results and serial antigen testing were problematic because test results were not available until weeks after the acute illness, and viral culturing for pneumonia could involve invasive sampling techniques to acquire. The availability of PCR testing has resulted in increased testing in general. The mechanism of PCR itself is more sensitive and specific because many viruses are notoriously difficult to grow in culture and are very sample dependent. 3. The positive feedback loop that results from improved viral pneumonia testing modalities The test availability results in an increased number of diagnoses. The increased number of diagnosis raises the clinical index of suspicion for the entity. The increased clinical index of suspicion raises the number of tests ordered. 4. The availability of safe, tolerable, and somewhat specific antiviral therapies Prior viral pneumonia treatment was essentially supportive measures only. Initial efforts at antiviral therapy were not well tolerated. The availability of some specific and effective treatments now spur earlier testing and a greater appreciation of the role of viral infection in pneumonia. Disease-modifying therapy for HIV is now available. 5. The increasing role of viral pathogens in pneumonia and the increased realization of the role of bacterial and viral co-infection necessitate a higher clinical index of suspicion and early identification of viral pulmonary pathogens. Counterbalance seeing this new clinical burden is the availability of the following Enhanced laboratory detection via ELISA and PCR testing modalities. Enhanced radiographic detection for a high thin section CAT scan. An increasing number of safe and efficacious antiviral drugs. Increased recognition of the role of prevention in viral infectious disease.

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Needlestick injuries are known to occur frequently in healthcare settings and can be serious. In North America, millions of healthcare workers use needles in their daily work, and hence, the risk of needlestick injuries is always a concern. While the introduction of universal precautions and safety conscious needle designs has led to a decline in needlestick injuries, they continue to be reported, albeit on a much smaller scale than in the past. Awareness of needlestick injuries started to develop soon after the identification of HIV in the early 1980s. However, today the major concern after a needlestick injury is not HIV but hepatitis B or hepatitis C. Guidelines have been established to help healthcare institutions manage needlestick injuries and when to initiate post-exposure HIV prophylaxis. The Centers for Disease Control and Prevention (CDC) has developed a model which helps healthcare professionals know when to start antiretroviral therapy. Needlestick injuries are an occupational hazard for millions of healthcare workers. Even though universal guidelines have decreased the risks of needlestick injuries over the past 30 years, these injuries continue to occur, albeit at a much lower rate. Healthcare professionals at the highest risk for needlestick injuries are surgeons, emergency room workers, laboratory room professionals, and nurses. The use of needles is unavoidable in healthcare, and even though every hospital has guidelines on proper handling and disposal of needles and the newest design of safety conscious needles, needlestick injuries continue to occur more often in et al. healthcare professionals like surgeons and emergency room personnel. In most cases, needlestick injuries occur chiefly because of unsafe practices and gross negligence on the part of the healthcare workers. The reality is that most needlestick injuries are preventable by following established procedures. Needlestick injuries came to the forefront of healthcare after the discovery of the HV in the early 1980s. Since the adoption of universal precautions, the number of needlestick injuries has greatly decreased but continues to occur, but the numbers are low. Today the major threat after a needlestick injury is not HIV but acquiring hepatitis B or hepatitis C. In the past, the majority of needlestick injuries occurred during resheathing of the needle after the withdrawal of blood from a patient. Even though this practice is now no longer recommended, there are experts in infectious disease who indicate that not resheathing the needle greatly increases the risk of needlestick injuries in house cleaners and porters who are in charge of collecting and disposing of the sharps containers. Over the years, many cases of cleaners and porters being injured by unsheathed needles have been reported. Further, this is more of a concern when healthcare workers ignore policies and discard needles directly into the plastic bags instead of the sharps containers. To prevent these injuries, many healthcare institutions have now adopted unique ways of resheathing needles. For example, in the operating room, there are now established protocols on how the nurse will pass sharp instruments and needles to the surgeon and vice versa. Another method of avoiding needlestick injuries is double gloving. Factors that increase the risk of exposure to body fluids