Cardiovascular Disease Risk Behaviors in Human Immunodeficiency Virus-Positive Populations: Exploring a Stress-Coping Hypothesis

Cardiovascular disease (CVD) risk behaviors, namely tobacco smoking, hazardous alcohol use, poor diet and sedentary behavior, are more prevalent among people living with HIV (PLWH) than the general population. Qualitative evidence shows that PLWH report adopting unhealthy behaviors as a means of coping with the stress of living with HIV, including the adverse physiological symptoms of HIV infection, the psychological stress of being aware of one’s HIV status, and the physiological and psychological impacts of being on HIV treatment. These observations suggest that being HIV-positive may have a causal influence on CVD risk behaviors and that these causal effects likely differ across stages of the HIV continuum. To date, few quantitative studies have been conducted to examine these causal relationships. The goal of this dissertation was to explore the effects of HIV continuum stage on CVD risk behaviors and assess several plausible stress-coping mechanisms, as motivated by established stress-coping theory. This dissertation consisted of three studies. First, a systematic review was conducted to examine the existing quantitative evidence for the causal effects of HIV continuum stage on CVD risk behaviors. Findings from this review revealed that being HIV-positive is associated with excess smoking and drinking, and that while receipt of a positive HIV diagnosis is associated with short-term improvements in some CVD risk behaviors, these improvements are unlikely to be maintained long-term. Overall, however, the existing studies suffer important methodological limitations, notably inadequate characterization of HIV continuum stage. The second study was an empirical analysis of patterns of self-reported CVD risk behaviors across the HIV continuum among a population-based sample of 4,061 adults aged 40 years and over living in rural Agincourt district in South Africa. Results showed no consistent evidence of an association between HIV continuum stage and hazardous alcohol use or sedentary behavior. However, higher prevalence of smoking was observed specifically among males who were HIV-positive and aware of their status but not on treatment, compared to those who were HIV-negative. There was no evidence of mediation by various measures of physiological and/or psychological stress. The third study was an analysis of whether perceived life expectancy (PLE) modifies the effects of HIV continuum stage on CVD risk behaviors. Observed associations were most prominent among individuals with low PLE and null among those with high PLE. Overall, this dissertation contributed to greater understanding of the relationship between CVD risk behaviors among HIV-infected persons across the HIV continuum. Findings did not support a stress-coping hypothesis; however, PLE was found to be a potentially useful indicator of individuals who are most likely to smoke in the presence of HIV. This dissertation also fills evidence gaps among older adults in sub-Saharan Africa, an under-studied population with high and increasing burdens of both HIV and CVD. As HIV-positive population survive longer on antiretroviral therapy and the prevention of age-related conditions becomes increasingly important, these findings may help inform future research and the development of CVD prevention interventions

On a linear optical implementation of non local product states and on their indistinguishability

In a recent paper Bennett et al.[Phys. Rev.A 59, 1070 (1999)] have shown the existence of a basis of product states of a bipartite system with manifest non-local properties. In particular these states cannot be completely discriminated by means of bilocal measurements. In this paper we propose an optical realization of these states and we will show that they cannot be completely discriminate by means of a global measurement using only optical linear elements, conditional transformation and auxiliary photons

The Acute and Persisting Impact of COVID-19 on Trajectories of Adolescent Depression: Sex Differences and Social Connectedness

Background The COVID-19 era is a time of unprecedented stress, and there is widespread concern regarding its short- and long-term mental health impact. Adolescence is a sensitive period for the emergence of latent psychopathology vulnerabilities, often activated by environmental stressors. The present study examined COVID-19′s impact on adolescent depression and possible influences of different domains of social connectedness (loneliness, social media use, social video game time, degree of social activity participation). Methods A community sample of 175 adolescents (51% boys, mean age = 16.01 years) completed questionnaires once before and twice during the COVID-19 pandemic. Piecewise growth modeling examined the acute (7 weeks) and persistent (8 months) effects of COVID-19 on depressive symptoms, and differences across sex and social connectedness. Results Significant increases in depressive symptoms followed pandemic onset for boys and girls. However, this increase was earlier and more pronounced among girls than boys, whose depression only increased significantly during the persistent period and to a lesser degree. Trajectories of depression were influenced by loneliness and social connections. Limitations Most participants had economic stability and minimal exposure to the virus. Exacerbation of depressive symptoms may be more severe in higher risk populations. Conclusions Adolescent depression levels have increased during COVID-19, and are higher for girls and those who are lonely. Enhanced screening and management for adolescent depression and social connectedness could play a critical role in mitigating the negative mental health fallout of COVID-19 and future pandemics within this population

Experiences of COVID-19-Related Racism and Impact on Depression Trajectories Among Racially/Ethnically Minoritized Adolescents

Purpose In 2020, racially/ethnically minoritized (REMD) youth faced the “dual pandemics” of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). Methods A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). Results REMD adolescents\u27 depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. Discussion REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth

Patterns of HIV Service Use and HIV Viral Suppression Among Patients Treated in an Academic Infectious Diseases Clinic in North Carolina

Irregular participation in HIV medical care hinders HIV RNA suppression and impacts health among people living with HIV. Cluster analysis of clinical data from 1,748 patients attending a large academic medical center yielded three HIV service usage patterns, namely: ‘engaged in care’, ‘sporadic care’, and ‘frequent use’. Patients ‘engaged in care’ exhibited most consistent retention (on average, >88 % of each patient’s observation years had ≥2 visits 90 days apart), annualized visit use (2.9 mean visits/year) and viral suppression (>73 % HIV RNA tests <400 c/mL). Patients in ‘sporadic care’ demonstrated lower retention (46–52 %), visit use (1.7 visits/year) and viral suppression (56 % <400 c/mL). Patients with ‘frequent use’ (5.2 visits/year) had more inpatient and emergency visits. Female, out-of-state residence, low attendance during the first observation year and detectable first-observed HIV RNA were early predictors of subsequent service usage. Patients ‘engaged in care’ were more likely to have HIV RNA <400 than those receiving sporadic care. Results confirm earlier findings that under-utilization of services predicts poorer viral suppression and health out-comes and support recommendations for 2–3 visits/year

Can the Success of HIV Scale-Up Advance the Global Chronic NCD Agenda?

Noncommunicable diseases (NCD) are the leading causes of death and disability worldwide but have received suboptimal attention and funding from the global health community. Although the first United Nations General Assembly Special Session (UNGASS) for NCD in 2011 aimed to stimulate donor funding and political action, only 1.3% of official development assistance for health was allocated to NCD in 2015, even less than in 2011. In stark contrast, the UNGASS on human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) in 2001 sparked billions of dollars in funding for HIV and enabled millions of HIV-infected individuals to access antiretroviral treatment. Using an existing analytic framework, we compare the global responses to the HIV and NCD epidemics and distill lessons from the HIV response that might be utilized to enhance the global NCD response. These include: 1) further educating and empowering communities and patients to increase demand for NCD services and to hold national governments accountable for establishing and achieving NCD targets; and 2) evidence to support the feasibility and effectiveness of large-scale NCD screening and treatment programs in low-resource settings. We conclude with a case study from Swaziland, a country that is making progress in confronting both HIV and NCD. In September 2011, the United Nations (UN) convened a UN General Assembly Special Session (UNGASS) on noncommunicable diseases (NCD). The event was the second UN High Level Meeting ever held for a health issue, following the successful UNGASS on human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) in 2001. Modeled after its predecessor, the 2011 meeting was intended to catalyze a response to what the World Health Organization (WHO) called an epidemic of “silent killers” that were the leading causes of death and disability worldwide, yet receive little attention from the global health community [1]. Looking back to the prior UNGASS on HIV/AIDS a decade earlier, the NCD meeting aspired to similar goals: rallying multisectoral and cross-national partnerships; stimulating robust donor funding; spurring ambitious targets and commitments on the part of national governments; and catalyzing rapid scale-up of NCD services in resource-limited settings [2]. Advocates highlighted similarities between chronic NCD and HIV/AIDS, including a stark mismatch between the burden of disease and available funding, and the need for programmatic innovation, continuity care, and health systems strengthening 3, 4 and 5. The UNGASS on NCD was successful at producing a Political Declaration to combat NCD [6], and many countries affirmed a commitment to ambitious NCD targets and to implementing evidence-based “best buys” 7 and 8. Yet 5 years later, the global NCD response has languished in what some have called an environment of “malignant neglect” [9]. Despite the fact that NCD account for 37% of disability-adjusted life years in low-income countries [10], only 1.3% of official development assistance for health was allocated to NCD in 2015 [11], a proportion that decreased between 2011 and 2015 [12]. Few resource-limited countries have operational national NCD strategies or adequate NCD services, awareness of and treatment-seeking rates for NCD have not improved [13], and the vast majority of people with cardiovascular disease, diabetes, cancer, and chronic respiratory disease remain undiagnosed and untreated 14 and 15. In contrast, in the years that followed the 2001 UNGASS, global spending on HIV increased by billions of dollars and the number of people initiating antiretroviral treatment (ART) in low- and middle-income countries soared from 400,000 in 2003 to nearly 17 million in 2015 [16]

Integrated vs. referred management of CVD risk factors for HIV positive patients on antiretroviral therapy in Swaziland

Cardiovascular disease risk factors (CVDRF) are prevalent in people living with HIV (PLHIV), but the optimal clinical management strategy for patients with both HIV and CVDRF in low resource settings is unknown. In some contexts, care for both HIV and CVDRF is provided in the HIV clinic (“integrated care”), which may be more convenient for patients. In others, PLHIV are referred to specialist clinics for management of their CVDRF (“referred care”) which may lead to higher quality CVDRF management. We compared integrated vs. referred strategies for patients with HIV and CVDRF at an urban health facility in Swaziland, exploring linkage to and retention in CVDRF care, intervention fidelity, and HIV and CVDRF-related health outcomes

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

How Can the Health System Retain Women in HIV Treatment for a Lifetime? A Discrete Choice Experiment in Ethiopia and Mozambique

Introduction: Option B+, an approach that involves provision of antiretroviral therapy (ART) to all HIV-infected pregnant women for life, is the preferred strategy for prevention of mother to child transmission of HIV. Lifelong retention in care is essential to its success. We conducted a discrete choice experiment in Ethiopia and Mozambique to identify health system characteristics preferred by HIV-infected women to promote continuity of care. Methods: Women living with HIV and receiving care at hospitals in Oromia Region, Ethiopia and Zambézia Province, Mozambique were shown nine choice cards and asked to select one of two hypothetical health facilities, each with six varying characteristics related to the delivery of HIV services for long term treatment. Mixed logit models were used to estimate the influence of six health service attributes on choice of clinics. Results: 2,033 women participated in the study (response rate 97.8% in Ethiopia and 94.7% in Mozambique). Among the various attributes of structure and content of lifelong ART services, the most important attributes identified in both countries were respectful provider attitude and ability to obtain non-HIV health services during HIV-related visits. Availability of counseling support services was also a driver of choice. Facility type, i.e., hospital versus health center, was substantially less important. Conclusions: Efforts to enhance retention in HIV care and treatment for pregnant women should focus on promoting respectful care by providers and integrating access to non-HIV health services in the same visit, as well as continuing to strengthen counseling

All-sky Search for High-Energy Neutrinos from Gravitational Wave Event GW170104 with the ANTARES Neutrino Telescope

Advanced LIGO detected a significant gravitational wave signal (GW170104) originating from the coalescence of two black holes during the second observation run on January 4$^{\textrm{th}}$, 2017. An all-sky high-energy neutrino follow-up search has been made using data from the ANTARES neutrino telescope, including both upgoing and downgoing events in two separate analyses. No neutrino candidates were found within $\pm500$ s around the GW event time nor any time clustering of events over an extended time window of $\pm3$ months. The non-detection is used to constrain isotropic-equivalent high-energy neutrino emission from GW170104 to less than $\sim4\times 10^{54}$ erg for a $E^{-2}$ spectrum