HIV Continuum of Care for Youth in the United States

BACKGROUND: Beneficial HIV treatment outcomes require success at multiple steps along the HIV Continuum of Care. Youth living with HIV are a key population, and sites in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) are known for modeling optimum HIV adolescent care. METHODS: A longitudinal cohort study conducted at 14 network sites across the United States assessed how the later steps of the Continuum of Care were achieved among the youth: engagement, treatment, and viral load (VL) suppression. Youth aged 13-24 who were behaviorally infected with HIV and linked to care at an ATN-affiliated site were eligible to participate. RESULTS: A total of 467 youth were enrolled and had 1 year of available data. Most were aged 22-24 (57%), male (79%), and black/non-Hispanic (71%). Most used alcohol (81%) and marijuana (61%) in the 3 months before enrollment, and 40% had a history of incarceration. Among this cohort of youth, 86% met criteria for care engagement; among these, 98% were prescribed antiretroviral therapy and 89% achieved VL suppression. Sustained VL suppression at all measured time points was found among 59% with initial suppression. Site characteristics were notable for the prevalence of adherence counseling (100%), case management (100%), clinic-based mental health (93%), and substance use (64%) treatment. CONCLUSIONS: Youth living with HIV in the United States can be successfully treated at health care sites with experience, excellence, and important resources and services. Sustained VL suppression may be an important step to add to the Continuum of Care for youth

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes.

Background- The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). Methods- This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: “fit/resilient”, “fit/non-resilient”, “frail/resilient” and “frail/non-resilient”. Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. Results- 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score &lt;61.60 were the phenotypes “frail/non-resilient” (OR=4.69, CI:2.08-10.55), “fit/non-resilient” (OR=2.79, CI:1.00-7.73). Predictors for EQ-5D-5L &lt;89.7% were the phenotypes “frail/non-resilient” (OR=5.93, CI: 2.64-13.33) and “frail/resilient” (OR=5.66, CI:1.93-16.54). Predictors of impaired IC (below the mean score value) were “frail/non-resilient” (OR=7.39, CI:3.20-17.07), and “fit/non-resilient” (OR=4.34, CI:2.16-8.71) phenotypes. Conclusions- Resilience is complementary to frailty in the identification of clinical phenotypes with different impact on wellness and QoL. Frailty and resilience should be evaluated in hospitalized COVID-19 patients to identify vulnerable individuals to prioritize urgent health interventions in people with PACS

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context.

The goal of this research was to examine associations among sociodemographic factors, HIV risk, and community context (e.g., economic insecurity, job training, housing instability, crime victimization, and perceived community norms) in adolescents and young adults who ever exchanged sex for drugs or money. Anonymous survey data were collected using ACASIs at community venues where adolescents and young adults congregate in resource-challenged, STI prevalent, urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact tests, and generalized estimating equations approaches were used to examine associations. Participants (1818, 95.5 % of those screened eligible) were, on average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual; 66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a number of variables (e.g., being male or transgender, homelessness, sex with a partner who has HIV, STI history, unemployment, job training access, housing instability, crime victimization, perceived community norms) that were significantly associated with exchange of sex (p &lt; 0.05). This research contributes to the knowledge-base regarding exchange of sex among adolescents and young adults, particularly as it relates to community context. Longitudinal studies to describe the trajectory of social, health, and physical risks and consequences are needed for development of effective evidence-based prevention strategies

Evaluation of the effect of human immunodeficiency virus-related structural interventions: the connect to protect project.

ImportanceWith the emphasis on structural-level interventions that target social determinants of human immunodeficiency virus (HIV) transmission to curb the HIV epidemic, there is a need to develop evaluation models that can detect changes in individual factors associated with HIV-related structural changes.ObjectiveTo describe whether structural changes developed and achieved by community coalitions are associated with an effect on individual factors associated with the risk of contracting HIV.Design, setting, and participantsIn this serial cross-sectional survey design, data were collected from 8 cities during 4 rounds of annual surveys from March 13, 2007, through July 29, 2010. Study recruitment took place at venues where the population of focus was known to congregate, such as clubs, bars, community centers, and low-income housing. The convenience sample of at-risk youth (persons aged 12-24 years) included 5337 individuals approached about the survey and 3142 (58.9%) who were screened for eligibility. Of the 2607 eligible participants, 2559 (98.2%) ultimately agreed to participate.InterventionsAchievement of locally identified structural changes that targeted public and private entities (eg, federal agencies, homeless shelters, and school systems) with the goal of fostering changes in policy and practice to ultimately facilitate positive behavioral changes aimed at preventing HIV.Main outcomes and measuresNumber of sexual partners, partner characteristics, condom use, and history of sexually transmitted infections and HIV testing.ResultsExposure to structural changes was not statistically significantly associated with any of the outcome measures, although some results were in the direction of a positive structural change effect (eg, a 10-unit increase in a structural change score had an odds ratio of 0.88 [95% CI, 0.76-1.03; P = .11] for having an older sexual partner and an odds ratio of 0.91 [95% CI, 0.60-1.39; P = .39] for using a condom half the time or less with a casual partner).Conclusions and relevanceThis study evaluated a broad representation of at-risk individuals and assessed the effect of numerous structural changes related to various HIV risk factors. No structural changes as measured in this study were associated with a statistically significant reduction in risk behaviors. These null findings underscore the need for a long-term approach in evaluating structural interventions and the development of more nuanced methods of quantifying and comparing structural-change initiatives and determining the appropriate strategies for evaluating effect