Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity

SummaryNeuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an “optimal” level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect

Geographic Variations in Retention in Care among HIV-Infected Adults in the United States

ObjectiveTo understand geographic variations in clinical retention, a central component of the HIV care continuum and key to improving individual- and population-level HIV outcomes.DesignWe evaluated retention by US region in a retrospective observational study.MethodsAdults receiving care from 2000–2010 in 12 clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) contributed data. Individuals were assigned to Centers for Disease Control and Prevention (CDC)-defined regions by residential data (10 cohorts) and clinic location as proxy (2 cohorts). Retention was ≥2 primary HIV outpatient visits within a calendar year, >90 days apart. Trends and regional differences were analyzed using modified Poisson regression with clustering, adjusting for time in care, age, sex, race/ethnicity, and HIV risk, and stratified by baseline CD4+ count.ResultsAmong 78,993 adults with 444,212 person-years of follow-up, median time in care was 7 years (Interquartile Range: 4–9). Retention increased from 2000 to 2010: from 73% (5,000/6,875) to 85% (7,189/8,462) in the Northeast, 75% (1,778/2,356) to 87% (1,630/1,880) in the Midwest, 68% (8,451/12,417) to 80% (9,892/12,304) in the South, and 68% (5,147/7,520) to 72% (6,401/8,895) in the West. In adjusted analyses, retention improved over time in all regions (p<0.01, trend), although the average percent retained lagged in the West and South vs. the Northeast (p<0.01).ConclusionsIn our population, retention improved, though regional differences persisted even after adjusting for demographic and HIV risk factors. These data demonstrate regional differences in the US which may affect patient care, despite national care recommendations

Comparative Effectiveness of Fish Oil Versus Fenofibrate, Gemfibrozil, and Atorvastatin on Lowering Triglyceride Levels Among HIV-Infected Patients in Routine Clinical Care

The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care

Adventurous Physical Activity Environments: A Mainstream Intervention for Mental Health

Adventurous physical activity has traditionally been considered the pastime of a small minority of people with deviant personalities or characteristics that compel them to voluntarily take great risks purely for the sake of thrills and excitement. An unintended consequence of these traditional narratives is the relative absence of adventure activities in mainstream health and well-being discourses and in large-scale governmental health initiatives. However, recent research has demonstrated that even the most extreme adventurous physical activities are linked to enhanced psychological health and well-being outcomes. These benefits go beyond traditional ‘character building’ concepts and emphasize more positive frameworks that rely on the development of effective environmental design. Based on emerging research, this paper demonstrates why adventurous physical activity should be considered a mainstream intervention for positive mental health. Furthermore, the authors argue that understanding how to design environments that effectively encourage appropriate adventure should be considered a serious addition to mainstream health and well-being discourse

β-Diversity and Species Accumulation in Antarctic Coastal Benthos: Influence of Habitat, Distance and Productivity on Ecological Connectivity

High Antarctic coastal marine environments are comparatively pristine with strong environmental gradients, which make them important places to investigate biodiversity relationships. Defining how different environmental features contribute to shifts in β-diversity is especially important as these shifts reflect both spatio-temporal variations in species richness and the degree of ecological separation between local and regional species pools. We used complementary techniques (species accumulation models, multivariate variance partitioning and generalized linear models) to assess how the roles of productivity, bio-physical habitat heterogeneity and connectivity change with spatial scales from metres to 100's of km. Our results demonstrated that the relative importance of specific processes influencing species accumulation and β–diversity changed with increasing spatial scale, and that patterns were never driven by only one factor. Bio-physical habitat heterogeneity had a strong influence on β-diversity at scales <290 km, while the effects of productivity were low and significant only at scales >40 km. Our analysis supports the emphasis on the analysis of diversity relationships across multiple spatial scales and highlights the unequal connectivity of individual sites to the regional species pool. This has important implications for resilience to habitat loss and community homogenisation, especially for Antarctic benthic communities where rates of recovery from disturbance are slow, there is a high ratio of poor-dispersing and brooding species, and high biogenic habitat heterogeneity and spatio-temporal variability in primary production make the system vulnerable to disturbance. Consequently, large areas need to be included within marine protected areas for effective management and conservation of these special ecosystems in the face of increasing anthropogenic disturbance

Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000–2010

Background. There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)–infected patients in care in the United States and Canada

Locative Media and Sociability:Using Location-Based Social Networks to Coordinate Everyday Life

Foursquare was a mobile social networking application that enabled people to share location with friends in the form of “check-ins.” The visualization of surrounding known social connections as well as unknown others has the potential to impact how people coordinate social encounters and forge new social ties. While many studies have explored mobile phones and sociability, there is a lack of empirical research examining location-based social network’s (LSBNs) from a sociability perspective. Drawing on a dataset of original qualitative research with a range of Foursquare users, the paper examines the application in the context of social coordination and sociability in three ways. First, the paper explores if Foursquare is used to organize certain social encounters, and if so, why. Second, the paper examines the visualization of surrounding social connections and whether this leads to “serendipitous encounters.” Lastly, the paper examines whether the use of Foursquare can produce new social relationships

Lessons Learned From the Design and Implementation of Myocardial Infarction Adjudication Tailored for HIV Clinical Cohorts

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995–2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus

Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

Introduction: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods: HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation