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T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across North America and Europe. While HLA-A∗02:01 was the most frequent HLA-A∗02 allele, others (A∗02:02, A∗02:03, A∗02:06) considerably increased HLA eligibility in Hispanic, Black, and Asian populations. Overall, MAGE-A4 prevalence based on clinical trial enrollment was 26% (447/1,750) across 10 solid tumor types, and was highest in synovial sarcoma (70%) and lowest in gastric cancer (9%). The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies.

Abstract Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.

Introduction: Durvalumab after concurrent chemoradiation (CCRT) for NSCLC improves survival, but only in a subset of patients. We investigated the effect of severe radiation-induced lymphopenia (sRIL) on survival in these patients. Methods: Outcomes after CCRT (2010–2019) or CCRT followed by durvalumab (2018–2019) were reviewed. RIL was defined by absolute lymphocyte count (ALC) nadir in samples collected at end of CCRT; sRIL was defined as nadir ALC less than 0.23 × 109/L (the lowest tertile). Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Cox proportional hazard modeling evaluated associations between clinical variables and survival. Results: Of 309 patients, 192 (62%) received CCRT only and 117 (38%) CCRT plus durvalumab. Multivariable logistic regression analysis indicated that sRIL was associated with planning target volume (OR = 1.002, p = 0.001), stage IIIB disease (OR = 2.77, p = 0.04), and baseline ALC (OR = 0.36, p < 0.01). Durvalumab extended median PFS (23.3 versus 14.1 mo, p = 0.003) and OS (not reached versus 30.8 mo, p < 0.01). sRIL predicted poorer PFS and OS in both treatment groups. Among patients with sRIL, durvalumab did not improve survival (median = 24.6 mo versus 18.1 mo CCRT only, p = 0.079). On multivariable analyses, sRIL (OR = 1.81, p < 0.01) independently predicted poor survival. Conclusions: Severe RIL compromises survival benefits from durvalumab after CCRT for NSCLC. Measures to mitigate RIL after CCRT may be warranted to enhance the benefit of consolidation durvalumab.

The early period of the COVID-19 pandemic limited access to HIV services for children and adolescents living with HIV (C/ALHIV). To determine progress in providing care and treatment services, we describe viral load coverage (VLC) and suppression (VLS) (

IntroductionStrong policy guidance has recently emerged identifying focal points at multiple levels and across sectors to end the persistent HIV pandemic and related inequities. Reducing the policy-implementation gap, as with the evidence-policy gap, requires strategic alignment between interventional research and policy realms. Global- and national-level HIV policy indicate a need for community-led efforts to reduce HIV stigma, and increase uptake of HIV prevention tools.MethodsThis study assesses a process-driven approach to facilitating community-led efforts to reduce HIV stigma, and build a generative context for community-led HIV prevention. The study intervention combines an adapted group-based microfinance process, a novel psychological curriculum, and leadership development at a scale now involving over 10,000 rural Kenyans across 39 villages.ResultsConsistent with interventional goals, and current relevant psychosocial theories, we find collective emotion, and HIV stigma (blame and discrimination) significantly improve with more time participating in the in the program and novel curriculum. Further, HIV stigma predicts subsequent reporting of ever being tested for HIV, and the intervention led to the development of “HIV prevention resource committees” – groups of participants committed to undergo training to reduce HIV stigma and prevent HIV within their communities.DiscussionImplications for further research to reduce the HIV policy-implementation gap are discussed, directly within this interventional context and more generally.

Neuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/

OBJECTIVES/GOALS: Alabama has the 3rd highest maternal mortality ratio in the U.S., with more than 50% of deaths occurring postpartum. There is little evidence on the prevalence or equity of postpartum care use in Alabama. This mixed methods study examines relationships between patient and provider factors and access to, use of, and racial disparities in postpartum care. METHODS/STUDY POPULATION: I will use a sequential explanatory mixed methods design. In the quantitative phase I will analyze an integrated electronic health record and human resource dataset to identify patient and provider factors that have a relationship with receipt of at least one postpartum visit within 12 weeks of delivery in a cross-sectional, retrospective cohort of 30,000 obstetric patients in Alabama. In the qualitative phase I will describe the postpartum experiences of obstetric patients who identify as Black or African American who received or did not receive at least one postpartum visit within 12 weeks of childbirth. In the integration phase I will draw synthesized conclusions about how the results of both phases describe predictors of and barriers and facilitators to postpartum care for Black birthing people in Alabama. RESULTS/ANTICIPATED RESULTS: I will identify relationships between patient factors (e.g., race, racial concordance with primary provider, insurance status, age, parity, type of delivery, Area Deprivation Index, presence of a chronic condition or severe morbidity) and patient receipt of postpartum care. I will also explore whether health care provider factors (e.g., race, racial concordance with the patient, age, gender, provider type, years of experience) predict patient receipt of postpartum care in this retrospective cohort. In the qualitative phase, I will explore the experiences and perceptions of birthing people who identify as Black or African-American that help explain the relationships between patient and provider factors and receipt of postpartum care identified in the quantitative phase. DISCUSSION/SIGNIFICANCE: More than 50% of maternal death occurs after childbirth. Postpartum care is critical to birthing people’s survival, especially in states with high maternal mortality. This study will fill a gap in knowledge about factors that have a relationship with equitable postpartum care in Alabama.

Adolescents who become pregnant during their secondary education experience a range of challenges that intersect and limit their opportunities to complete schooling and take up university places. One approach to addressing this issue at an Australian regional university is through the Tertiary Preparation Pathway (TPP) which has been delivered within the Supporting Teenagers with Education, Mothering, and Mentoring (STEMM) program, since 2008. The STEMM program offers teen mothers an opportunity to continue or re-engage with education during and beyond pregnancy. Adopting an intersectionality lens, interviews with adolescent mothers identified three key elements underpinning the success of the TPP/STEMM program: recognising the educational aspirations of teen mothers, developing agency and independence and promoting a strong sense of self. This article aims to provide practical implications for educators wishing to establish or develop programs based on this transformative teaching.

Abstract Stigma in health facilities undermines diagnosis, treatment, and successful health outcomes. Addressing stigma is fundamental to delivering quality healthcare and achieving optimal health. This correspondence article seeks to assess how developments over the past 5 years have contributed to the state of programmatic knowledge—both approaches and methods—regarding interventions to reduce stigma in health facilities, and explores the potential to concurrently address multiple health condition stigmas. It is supported by findings from a systematic review of published articles indexed in PubMed, Psychinfo and Web of Science, and in the United States Agency for International Development’s Development Experience Clearinghouse, which was conducted in February 2018 and restricted to the past 5 years. Forty-two studies met inclusion criteria and provided insight on interventions to reduce HIV, mental illness, or substance abuse stigma. Multiple common approaches to address stigma in health facilities emerged, which were implemented in a variety of ways. The literature search identified key gaps including a dearth of stigma reduction interventions in health facilities that focus on tuberculosis, diabetes, leprosy, or cancer; target multiple cadres of staff or multiple ecological levels; leverage interactive technology; or address stigma experienced by health workers. Preliminary results from ongoing innovative responses to these gaps are also described. The current evidence base of stigma reduction in health facilities provides a solid foundation to develop and implement interventions. However, gaps exist and merit further work. Future investment in health facility stigma reduction should prioritize the involvement of clients living with the stigmatized condition or behavior and health workers living with stigmatized conditions and should address both individual and structural level stigma.

Recent discourse about engaging first year students calls for more collaboration in terms of adopting a holistic approach to course delivery and support. This paper discusses a collaborative support model operating at a regional Australian university since 2008. In particular, it describes a collaborative support initiative emerging from this model that is based on providing an informal consultative space where students can drop-in and gain assessment support for research, writing and content. A focus group, online surveys and interviews with co-ordinators were conducted to evaluate the impact of this initiative. Findings suggest that this collaborative support model impacts on the first year student experience by: raising awareness about academic skills and the processes for researching and writing; promoting peer learning opportunities; building confidence and providing suitable support for a diverse range of students.

The vulnerability of women to HIV infection makes establishing predictors of women's involvement in extra-marital partnerships critical. We investigated the predictors of extra-marital partnerships among women married to fishermen.The current analyses are part of a mixed methods cross-sectional survey of 1090 gender-matched interviews with 545 couples and 12 focus group discussions (FGDs) with 59 couples. Using a proportional to size simple random sample of fishermen as our index participants, we asked them to enrol in the study with their spouses. The consenting couples were interviewed simultaneously in separate private rooms. In addition to socio-economic and demographic data, we collected information on sexual behaviour including extra-marital sexual partnerships. We analysed these data using descriptive statistics and multivariate logistic regression. For FGDs, couples willing to participate were invited, consented and separated for simultaneous FGDs by gender-matched moderators. The resultant audiofiles were transcribed verbatim and translated into English for coding and thematic content analysis using NVivo 9.The prevalence of extra-marital partnerships among women was 6.2% within a reference time of six months. Factors that were independently associated with increased likelihood of extra-marital partnerships were domestic violence (aOR, 1.45; 95% CI 1.09-1.92), women reporting being denied a preferred sex position (aOR, 3.34; 95% CI 1.26-8.84) and spouse longer erect penis (aOR, 1.34; 95% CI 1.00-1.78). Conversely, women's age--more than 24 years (aOR, 0.33; 95% CI 0.14-0.78) and women's increased sexual satisfaction (aOR, 0.92; 95% CI 0.87-0.96) were associated with reduced likelihood of extra-marital partnerships.Domestic violence, denial of a preferred sex positions, longer erect penis, younger age and increased sexual satisfaction were the main predictors of women's involvement in extra-marital partnerships. Integration of sex education, counselling and life skills training in couple HIV prevention programs might help in risk reduction.

Although a few researchers mention that involving interpreters can have an impact on the research process and research findings, little is published regarding methods of assessing the interpretation work's quality and impact. The impact of lay volunteer interpreters used in audiorecorded semistructured interviews on collecting data and the data quality and subsequent analysis is examined. A new systematic approach is presented comparing original interview transcripts (conducted with volunteer interpreters) with independent transcripts, reinterpretations by professional interpreters. Findings indicate that involving volunteer interpreters had an impact on the validity and reliability of a portion of the data, the subsequent analysis, and some practical research aspects. Researchers involving interpreters should pay careful attention to the interpreters' influence on the research, the data produced, and critically bring this to bear in their analysis and interpretation. The systematic comparative approach is a cost-effective tool that can be used successfully to examine the influence's effects.

Three cases of immune thrombocytopenia (ITP) associated with human immunodeficiency virus (HIV) infection prompted a review of community-acquired thrombocytopenia in Nova Scotia from January 1980 to December 1987. Two hundred and seven patients meeting the case definition of ITP were identified. The incidence of ITP rose from 2.0×105 in 1980 to 3.3×105 in 1987. More cases of ITP in the sexually active population occurred between 1984 and 1987 than in the previous four years (P=0.034). All three cases of known HIV associated ITP were captured in the retrospective surveillance system. The study concluded that increases in community-acquired ITP in a sexually active population may be a surrogate marker of the HIV epidemic, even in geographic areas with a low seroprevalence for HIV. Serological tests for HIV infection should be a routine part of the diagnostic investigation of ITP in all sexually active patients or those with other potential risk factors for HIV infection.