Examining adherence barriers among women with HIV to tailor outreach for long-acting injectable antiretroviral therapy

Background Long-acting (LA) injectable antiretroviral therapy (ART) has been found non-inferior to daily oral ART in Phase 3 trials. LA ART may address key barriers to oral ART adherence and be preferable to daily pills for some people living with HIV. To date, women have been less represented than men in LA ART research. Using longitudinal data from the Women’s Interagency HIV Study (WIHS) cohort of women living with HIV in the United States, we examined barriers and facilitators of daily oral ART adherence that may be related to or addressed by LA ART. Methods We conducted a secondary analysis of WIHS cohort data from 1998 to 2017 among participants seen for at least 4 visits since 1998 who reported using ART at least once (n = 2601). Two dichotomous outcomes, patient-reported daily oral ART adherence and viral suppression were fit using generalized linear models, examining the role of socio-demographic and structural factors. Results At study enrollment, the median age was 40.5 years, 63% of participants were African American and 22% were Latina. The majority (82%) reported taking ART more than 75% of the time and 53% were virally suppressed. In multivariate analysis, several sub-groups of women had lower odds of reported adherence and viral suppression: 1) younger women (adherence aOR: 0.71; viral suppression aOR: 0.63); 2) women who inject drugs (adherence aOR: 0.38; viral suppression aOR: 0.50) and those with moderate (adherence aOR: 0.59; viral suppression aOR: 0.74) and heavy alcohol consumption (adherence aOR: 0.51; viral suppression aOR: 0.69); 3) those with depressive symptoms (adherence aOR: 0.61; viral suppression aOR: 0.76); and 4) those with a history of going on and off ART (adherence aOR: 0.62, viral suppression aOR: 0.38) or changing regimens (adherence aOR: 0.83, viral suppression aOR: 0.56). Conclusions Current injectable contraceptive users (vs. non-users) had greater odds of oral ART adherence (aOR: 1.87) and viral suppression (aOR: 1.28). Findings identify profiles of women who may benefit from and be interested in LA ART. Further research is warranted focused on the uptake and utility of LA ART for such key subpopulations of women at high need for innovative approaches to achieve sustained viral suppression

BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study

Background Our knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease relapses (flares), converting diseases from inactive to active states. Focussing on rheumatoid arthritis (RA), the challenge that we will address is why IMIDs remit and relapse. Extrapolating from pathogenetic factors involved in disease initiation, new episodes of inflammation could be triggered by recurrent systemic immune dysregulation or locally by factors within the joint, either of which could be endorsed by overarching epigenetic factors or changes in systemic or localised metabolism. Methods The BIO-FLARE study is a non-randomised longitudinal cohort study that aims to enrol 150 patients with RA in remission on a stable dose of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), who consent to discontinue treatment. Participants stop their DMARDs at time 0 and are offered an optional ultrasound-guided synovial biopsy. They are studied intensively, with blood sampling and clinical evaluation at weeks 0, 2, 5, 8, 12 and 24. It is anticipated that 50% of participants will have a disease flare, whilst 50% remain in drug-free remission for the study duration (24 weeks). Flaring participants undergo an ultrasound-guided synovial biopsy before reinstatement of previous treatment. Blood samples will be used to investigate immune cell subsets, their activation status and their cytokine profile, autoantibody profiles and epigenetic profiles. Synovial biopsies will be examined to profile cell lineages and subtypes present at flare. Blood, urine and synovium will be examined to determine metabolic profiles. Taking into account all generated data, multivariate statistical techniques will be employed to develop a model to predict impending flare in RA, highlighting therapeutic pathways and informative biomarkers. Despite initial recruitment to time and target, the SARS-CoV-2 pandemic has impacted significantly, and a decision was taken to close recruitment at 118 participants with complete data. Discussion This study aims to investigate the pathogenesis of flare in rheumatoid arthritis, which is a significant knowledge gap in our understanding, addressing a major unmet patient need

Spondylarthropathies (including psoriatic arthritis): 244. Validity of Colour Doppler and Spectral Doppler Ultrasound of Sacroilicac Joints Againts Physical Examination as Gold Standard

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI) < 0.75 within the SJ area were present. Statistical analysis was performed estimating sensitivity and specificity against gold standard. The Kappa correlation coefficient was used for reliability study. Results: 106 cases (53 female, 55 male; mean age 36 10 years) were studied. There were no statistical differences between groups related to age or sex. Physical examination of SJ was positive in 38 patients (59 sacroiliac joints). US detected Doppler signal within SJ in 37 patients (58 SJ): 33 of them were symptomatic SpA (52 SJ), one of them were asymptomatic SpA (1 SJ) and one was a healthy control (1 SJ). The accuracy of US when compared to clinical data as gold standard at subject level in the overall group was: sensitivity of 68.6% and specificity of 85.7%, positive predictive value of 70.5% and negative predictive value of 84.5%. A positive likelihood ratio of 4.8, a negative likelihood ratio of 0.36 and a kappa coefficient of 0.55 were achieved. Conclusions: Doppler US of SJ seems to be a valid method to detect active SJ inflammation. Disclosure statement: The authors have declared no conflicts of interes

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Signature Work in Action: Senior Capstones Prepare Students for Unscripted Challenges

More than twenty years ago, administrators and faculty at Portland State University (PSU) boldly enacted a comprehensive reform of our general education program in order to create more meaningful and relevant educational pathways for our students. The result was a four-year general education program, University Studies, which mirrors nearly identically the “guided pathway with signature work” model proposed by the Association of American Colleges and Universities. Each University Studies course across four levels is required to address four goals: communication, critical thinking, ethics and social responsibility, and appreciation of the diversity of the human experience. During the first year, each student engages in Freshman Inquiry: an interdisciplinary, theme-based exploration of an important topic organized through courses such as Globalization, Race and Social Justice, and Sustainability. Following Freshman Inquiry, students complete three sophomore-level theme-based courses and three junior-level cluster courses, through which they rigorously examine substantial topics in courses such as Leading Social Change, Global Perspectives, Gender and Sexuality Studies, and Design Thinking/Innovation/Entrepreneurship. In the first and second years, peer and graduate mentors are key to the curriculum, facilitating small-group sessions and enhancing peer-to-peer learning. At the senior level, University Studies culminates in a seminar-style, interdisciplinary, community-based-learning Capstone course, which serves as students’ “signature experience.” PSU engages over 4,400 students in 220 Capstone courses annually, making ours the largest documented capstone program in the nation. In research conducted at PSU, students overwhelmingly reported that their Capstone was one of the most significant learning experiences in their undergraduate education

In Service Together: University Students and Incarcerated Youth Collaborate for Change

Through the lens of two courses at Portland State University (PSU), this article addresses critical service learning pedagogy as transformational for both incarcerated youth and university students. In one course, PSU students share a writing/art workshop with youth in juvenile detention though The Beat Within (https://www.thebeatwithin.org). Another course brings together PSU students and young men incarcerated at MacLaren Youth Correctional Facility in an inside/out course format (https://www.insideoutcenter.org). Working collaboratively, students have developed a variety of service-learning projects. This article explores the impact of critical service learning courses on both incarcerated young people and university students