Evolving AIDS- and non-AIDS Mortality and Predictors in the PISCIS Cohort of People Living With HIV in Catalonia and the Balearic Islands (Spain), 1998-2020.

Background: Effective antiretroviral therapy (ART) has substantially reduced acquired immunodeficiency syndrome (AIDS)-related deaths, shifting the focus to non-AIDS conditions in people living with human immunodeficiency virus (HIV) (PLWH). We examined mortality trends and predictors of AIDS- and non-AIDS mortality in the Population HIV Cohort from Catalonia and Balearic Islands (PISCIS) cohort of PLWH from 1998 to 2020. Methods: We used a modified Coding Causes of Death in HIV protocol, which has been widely adopted by various HIV cohorts to classify mortality causes. We applied standardized mortality rates (SMR) to compare with the general population and used competing risks models to determine AIDS-related and non-AIDS-related mortality predictors. Results: Among 30 394 PLWH (81.5% male, median age at death 47.3), crude mortality was 14.2 per 1000 person-years. All-cause standardized mortality rates dropped from 9.6 (95% confidence interval [CI], 8.45-10.90) in 1998 through 2003 to 3.33 (95% CI, 3.14-3.53) in 2015 through 2020, P for trend = .0001. Major causes were AIDS, non-AIDS cancers, cardiovascular disease, AIDS-defining cancers, viral hepatitis, and nonhepatitis liver disease. Predictors for AIDS-related mortality included being aged ≥40 years, not being a man who have sex with men, history of AIDS-defining illnesses, CD4 < 200 cells/µL, ≥2 comorbidities, and nonreceipt of ART. Non-AIDS mortality increased with age, injection drug use, heterosexual men, socioeconomic deprivation, CD4 200 to 349 cells/µL, nonreceipt of ART, and comorbidities, but migrants had lower risk (adjusted hazard risk, 0.69 [95% CI, .57-.83]). Conclusions: Mortality rates among PLWH have significantly decreased over the past 2 decades, with a notable shift toward non-AIDS-related causes. Continuous monitoring and effective management of these non-AIDS conditions are essential to enhance overall health outcomes.

Active tuberculosis incidence among treatment failure experienced patients in North Wollow Zone: A multicenter historical cohort.

Background: In Ethiopia, tuberculosis (TB) is a significant cause of death among individuals living with HIV, especially in resource-limited areas and those who have experienced treatment failure. However, there is the paucity of data regarding TB among treatment failures experienced people living with HIV. This study aimed to estimate the rate and identify predictors of tuberculosis among patients who received second-line treatment in North Wollo, Northeast Ethiopia. Methods: A retrospective follow-up study was conducted on 474 HIV-infected patients who experienced treatment failure. The study period ranged from January 2015 to September 30, 2021. The incidence of TB was assessed using a Cox proportional hazard regression model, after ensuring that all assumptions were met. Factors associated with active TB were determined by analyzing adjusted hazard ratios and 95% confidence intervals. Results: In a study of 474 HIV-positive patients on second-line antiretroviral treatment, we found an incidence rate of 3.6% with 17 new cases of TB observed over 4412.4 persons per year (PPY). The overall incidence density rate was estimated to be 0.39 cases per 100 PPY (95% CI: 0.239-0.618). Regarding the occurrence of active TB in second-line patients, WHO clinical treatment stage (T3 and T4), missed isoniazid preventive therapy had a significantly higher risk (AHR: 13.225, 95% CI: 2.894-60.434, p = 0.001), while being married was associated with a lower risk (AHR: 0.203, 95% CI: 0.045-0.907, p = 0.001). Conclusion: A high incidence of active TB was observed shortly after initiating second-line antiretroviral treatment. Factors such as being in the WHO clinical treatment stage (T3 and T4) and marital status were determinants for active TB. To improve overall survival rates, it is vital to enhance early TB screening and implement effective isoniazid preventive therapy.

Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.

People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts, however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4, CD8 T-cells, nadir CD4 count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197-PWH with median age of 42-years, using a 56-gene panel. Seventy-nine percent had a CD4 nadir < 200, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8 T-cells and nadir CD4 counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of ≥ 35-years-old patients. Inflammatory biomarkers were higher in CH carriers compared to non-carriers supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4 and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.

Diagnosis and Risk Factors of Prediabetes and Diabetes in People Living with HIV- Evaluation of Clinical and Microbiome Parameters.

Diabetes is more common among people living with HIV (PLWH), as compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%) and diabetic (6.9%) PLWH. HbA1c and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher BMI, Ethiopian origin, HIV duration, lower integrase inhibitor exposure and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1C likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation.

Improving 1-Year Mortality Following Intensive Care Unit Admission in Adults with HIV: A 20-Year Observational Study.

BACKGROUND: Despite widespread use of combination antiretroviral therapy, people with HIV (PWH) continue to have an increased risk of admission to and mortality in the intensive care unit (ICU). Mortality risk after hospital discharge is not well described. Using retrospective data on adult PWH (≥18 years) admitted to ICU from 2000-2019 in an HIV-referral centre, we describe trends in 1-year mortality after ICU admission. METHODS: One-year mortality was calculated from index ICU admission to date of death; with follow-up right-censored at day 365 for people remaining alive at 1 year, or day 7 after ICU discharge if lost-to-follow-up after hospital discharge. Cox regression was used to describe the association with calendar year before and after adjustment for patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation II [APACHE II] score, CD4+ T-cell count, and recent HIV diagnosis) at ICU admission. Analyses were additionally restricted to those discharged alive from ICU using a left-truncated design, with further adjustment for respiratory failure at ICU admission in these analyses. RESULTS: Two hundred and twenty-one PWH were admitted to ICU (72% male, median [interquartile range] age 45 [38-53] years) of whom 108 died within 1-year (cumulative 1-year survival: 50%). Overall, the hazard of 1-year mortality was decreased by 10% per year (crude hazard ratio (HR): 0.90 (95% confidence interval: 0.87-0.93)); the association was reduced to 7% per year (adjusted HR: 0.93 (0.89-0.98)) after adjustment. Conclusions were similar among the subset of 136 patients discharged alive (unadjusted: 0.91 (0.84-0.98); adjusted 0.92 (0.84, 1.02)). CONCLUSIONS: Between 2000 and 2019, 1-year mortality after ICU admission declined at this ICU. Our findings highlight the need for multi-centre studies and the importance of continued engagement in care after hospital discharge among PWH.

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling.

BACKGROUND: HIV drug resistance (DR) is a growing threat to the durability of current and future HIV treatment success. DR testing (DRT) technologies are very expensive and specialised, relying on centralised laboratories in most low and middle-income countries. Modelling for laboratory network with point-of-care (POC) DRT assays to minimise turnaround time (TAT), is urgently needed to meet the growing demand. METHODS: We developed a model with user-friendly interface using integer programming and queueing theory to improve the DRT system in Kisumu County, Kenya. We estimated DRT demand based on both current and idealised scenarios and evaluated a centralised laboratory-only network and an optimised POC DRT network. A one-way sensitivity analysis of key user inputs was conducted. RESULTS: In a centralised laboratory-only network, the mean TAT ranged from 8.52 to 8.55 working days, and the system could not handle a demand proportion exceeding 1.6%. In contrast, the mean TAT for POC DRT network ranged from 1.13 to 2.11 working days, with demand proportion up to 4.8%. Sensitivity analyses showed that expanding DRT hubs reduces mean TAT substantially while increasing the processing rate at national labs had minimal effect. For instance, doubling the current service rate at national labs reduced the mean TAT by only 0.0%-1.9% in various tested scenarios, whereas doubling the current service rate at DRT hubs reduced the mean TAT by 37.5%-49.8%. In addition, faster batching modes and transportation were important factors influencing the mean TAT. CONCLUSIONS: Our model offers decision-makers an informed framework for improving the DRT system using POC in Kenya. POC DRT networks substantially reduce mean TAT and can handle a higher demand proportion than a centralised laboratory-only network, especially for children and pregnant women living with HIV, where there is an immediate push to use DRT results for patient case management.

Experiences and resultant care gaps among women with HIV in Canada: concept mapping the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) findings.

OBJECTIVES: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps. DESIGN: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS. SETTING: British Columbia, Ontario and Quebec, Canada. PARTICIPANTS: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers. RESULTS: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV. CONCLUSIONS: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV.

Middle-aged and older adults in Aids village: a mixed methods study on talking about death and well-being promotion based on social support theory.

Introduction: Will about talking about death bring well-being? This study aims to explore the impact of talking about death on the subjective well-being of the rural middle-aged and older adults in China's "Aids village" from five dimensions: the way of talking about death, the attitude towards talking about death, the objects of talking about death with, the frequency of talking about death and the content of the death talk, and investigate whether social support played a mediating role during this process. Methods: A field survey and in-depth interviews were conducted in Wen Lou village (a famous Chinese "Aids village"), and valid questionnaires were completed by the HIV/Aids-affected middle-aged and older adults. A series of linear regression analyses were conducted to detect whether the way of talking about death, the attitude towards talking about death, the objects of talking about death with, the frequency of talking about death and the content of the death talk predict the subjective well-being of the HIV/Aids-affected middle-aged and older adults. An empirical test for mediation effect was performed to examine whether social support played a mediating role during the process. Results: It was found that the more frequent the middle-aged and older adults talk about death, the higher level of their subjective well-being is (ΔR2 = 0.056, 0.05 < p < 0.10), and during which process social support played a mediating role. Discussion: The author believes that using "talking about death" as a kind of medical intervention, carrying out corresponding life education and death education, and developing a suitable hospice care model, may be a valuable way for the HIV/Aids-affected middle-aged and older adults in the rural area.

Evaluation of Usage of Different Diagnostic Aids for Oral Cancer by Oral and Maxillofacial Surgeons: An Original Research.

Objective: The purpose of this study was to assess how oral and maxillofacial surgeons used various diagnostic tools for oral cancer. Materials and Methods: A cross-sectional methodology was used, and a standardized questionnaire was given to oral and maxillofacial surgeons randomly chosen sample. The questionnaire gathered information on demographics and the use of diagnostic tools. Data analysis methods included Chi-square testing and descriptive statistics. Results: The study included 200 oral and maxillofacial surgeons in total. The most often used diagnostic tool (95%) was visual inspection, followed by toluidine blue staining (48%) and brush biopsy (32%). Less frequently used were newer methods like optical coherence tomography (12.5%) and autofluorescence imaging (15%). No significant correlations between demographic factors and patterns of use of diagnostic tools were found by Chi-square tests. Conclusion: The results show that oral and maxillofacial surgeons frequently use brush biopsy, toluidine blue staining, and ocular evaluation. However, there is a need for more widespread adoption of cutting-edge technologies. By removing obstacles and offering training opportunities, one can increase the use of diagnostic tools, improving patient outcomes and the diagnosis of oral cancer.

Metagenomic next-generation sequencing assistance in identifying Mycobacterium avium meningoencephalitis: A case report and literature review.

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.

Co-creation of a health literate-sensitive training and conversation aid to support shared decision-making in maternity care.

Background: Maternity care increasingly aims to achieve Shared Decision-making (SDM), yet seemingly not to the benefit of clients with low health literacy (HL). We developed an SDM training for healthcare professionals (HCPs) and a conversation aid to support HL-sensitive SDM in maternity care. Methods: The training and conversation aid were based on previous needs assessments and expert consultation, and were developed in co-creation with clients (n = 15) and HCPs (n = 7). Usability, acceptability and comprehension of the conversation aid were tested among new clients (n = 14) and HCPs (n = 6). Acceptability of the training was tested among midwifery students (n = 5). Results: In the co-creation sessions, clients reported to expect that their midwife becomes acquainted with their general values, priorities and daily context. Clients also emphasized wanting to be supported in their preferred decisional role. User test interviews showed that clients and HCPs were positive towards using the conversation aid, but also apprehensive about the time it required. The user test of the training showed that more attention was needed for recognizing and adapting information provision to clients' HL level. Conclusion and innovation: The newly developed conversation aid and training have potential to support HCPs and clients in HL-sensitive SDM.

How Intimate Partner Violence Is Influenced by Social Identity Among Sexual Minority Men.

Purpose: Sexual minority men (SMM) experience intimate partner violence (IPV) at disproportionately high rates. The objective of this article was to identify the experiences of SMM and health care providers on how social identity impacts IPV. Methods: SMM participants (N = 23) were recruited from online community settings and a lesbian, gay, bisexual, transgender, queer, and others (LGBTQ+) organization in Los Angeles; providers (N = 10) were recruited from LGBTQ+ organizations. Semistructured interviews were audio recorded and transcribed verbatim. An applied thematic analysis approach was implemented to create memos, inductively generate a codebook, apply codes to the transcripts, and identify key themes in data. Results: Three main themes were identified. The first theme was weaponizing social identity to control a partner, which had three subthemes: (1) immigration status, race/ethnicity, and skin color, (2) threatening to "out" the partner's sexual orientation, and (3) abusing power inequity. Men who perpetrated IPV often used minority identities or undisclosed sexuality to leverage power over their partner. The second theme was use of IPV to establish masculinity, by exerting power over the more "feminine" partner. The third theme was internalized homophobia as a root cause of IPV, which details how internalized homophobia was often expressed in violent outbursts toward partners. Conclusion: These findings highlight how IPV among SMM can be influenced by social and sexual identity. Future research must consider socially constructed power structures and the multiple identities of SMM when developing interventions to address IPV in this population.

[Clustering of cognitive domains among older adults with HIV]. / Agrupación de dominios cognitivos en personas mayores con VIH.

Background: Age and HIV are synergistic risk factors for conditions such as HIV-associated neurocognitive disorders (HAND). Yet, it is unclear whether OAWH display different cognitive profiles for HAND. Objective: To describe the cognitive patterns of OAWH treated with combined antiretroviral therapy (cART). Methods: Cross-sectional study that included 330 participants with HIV, aged 50 years or older, cared for at a tertiary care hospital in Mexico City. A short neuropsychological test battery was used to assess a wide spectrum of cognitive functions. The optimal number of cognitive clusters was determined by the silhouette method and a minimization of the Bayesian information criterion. Results: Participants' mean age was 58.8 years (SD = 6.6), and 12.1% were women. A 3-cluster solution yielded stable Jaccard coefficients (p > 0.70). Cluster 1 showed more significant impairment in visual and verbal memory domains, whereas participants in cluster 3 showed significant impairment in language, and abstraction. Cluster 2 showed no predominance of any domain for alterations. Conclusions: There are different cognitive profiles among OAWH with HAND. These differences may be due to individual patterns of HIV-related and non-HIV-related factors.

Antecedentes: La edad y el VIH constituyen factores de riesgo sinérgicos de afecciones como los trastornos neurocognitivos asociados al VIH (TNAV). No se ha esclarecido si las personas mayores con VIH presentan perfiles cognitivos diferentes en caso de padecer TNAV. Objetivo: Describir los patrones cognitivos de adultos mayores con VIH tratados con terapia antirretroviral combinada (TARc). Métodos: Estudio transversal que incluyó a 330 participantes con VIH, de 50 años o más, atendidos en un centro hospitalario de tercer nivel en la Ciudad de México. Se utilizó una batería neuropsicológica corta estandarizada a fin de evaluar un amplio espectro de funciones cognitivas. Se determinó el número óptimo de grupos de dominios cognitivos a partir del método de la silueta y minimización del criterio de información bayesiano. Resultados: La edad promedio de los participantes fue de 58.8 años; las mujeres constituyeron 12.1 %. Una solución de tres grupos produjo coeficientes de Jaccard estables (p > 0.70). El grupo 1 mostró deterioro más significativo en la memoria visual y verbal, en tanto que el grupo 3 mostró deterioro significativo en el lenguaje y la abstracción. En el grupo 2 no se registró predominio de ningún dominio en cuanto a alteraciones. Conclusiones: Existen perfiles cognitivos diferentes entre las personas mayores con VIH y TNAV. Estas diferencias pueden deberse a patrones individuales de factores relacionados o no con el VIH.

What may encourage or deter health services utilization by people living with or at the risk of HIV/AIDS in special health centers? Qualitative evidence from a stigmatized community.

BACKGROUND: Behavioral Diseases Counseling Centers (BDCCs) and Vulnerable Women's Counseling Centers (VWCCs) in Iran are the main peripheral centers that offer educational, counseling, diagnostic, preventive, curative and protective services to individuals living with or at high risk of contracting HIV/AIDS and female sex workers respectively. Due to the social stigma surrounding HIV in Iran, this study aims to identify the factors that may hinder or encourage HIV/AIDS patients and women with risky sexual behaviors from visiting these centers. METHODS: Conducted in 2023, this qualitative study involved individuals visiting BDCCs and VWCCs in two western provinces of Iran, Ilam and Kermanshah. The study participants included 21 health staff members working in BDCCs and VWCCs and 20 HIV/AIDS patients and vulnerable women with unsafe sexual behaviors referring to these centers. Purposive, snowball and maximum variation sampling techniques were applied to interview the participants. Interviews were conducted between January 5th and May 21st, 2023, using a semi-structure guideline. Interviews were transcribed and content analysis approach was applied to analyze data using MAXQDA20 software. RESULTS: According to the findings, the barriers and facilitators of visiting specialized centers for HIV/AIDS patients and vulnerable women were categorized into three main categories, 10 subcategories and 35 sub-subcategories including: Medical and operational processes (4 subcategories and 12 sub-subcategories), mutual interactions between the personnel and visitors (people living with and at the risk of getting HIV/AIDS) (3 subcategory and 13 sub-subcategories), and physical characteristics of the centers (3 subcategories and 10 sub-subcategories). CONCLUSIONS: To improve the performance of BDCCs and VWCCs and encourage people living with and at the risk of contracting HIV/AIDS to visit these centers regularly, health policy makers should consider modifying clinical processes, physical features, personnel behaviors and visitors' concerns raised by the interviewees and the issues identified in this study.

Comprehensive HIV knowledge and associated factors among reproductive-age women: analysis of the Gambia Demographic and Health Survey 2019/2020.

INTRODUCTION: Globally, there are 37.7 million people living with human immunodeficiency virus (HIV). So far, there is no study done in Gambia which assessed comprehensive HIV knowledge and its associated factors. Therefore, this study aims to assess comprehensive HIV knowledge and its associated factors among reproductive-age women in Gambia. OBJECTIVE: To assess the prevalence of comprehensive HIV knowledge and its associated factors among reproductive-age women in Gambia. METHODS: The study used the Gambian Demographic and Health Survey, which was conducted from 21 November 2019 to 30 March 2020 in Gambia. The survey employed a stratified two-stage cluster sampling technique to recruit study participants. Logistic regression analysis was used to identify factors associated with HIV comprehensive knowledge. Statistical significance was declared at a P value of less than 0.05 with a 95% confidence interval (CI). RESULTS: The overall prevalence of comprehensive HIV knowledge was 27.1% (25.1-36.2%). Older age [adjusted odds ratio (AOR) of 1.20 (95% CI 1.16-1.26)], using contraceptive [AOR of 1.15 (95% CI 1.01-1.31)], higher education [AOR of 4.73 (95% CI 3.86-5.81)], rich wealth quintile [AOR of 1.61 (95% CI 1.37-1.87)], media exposure [AOR of 1.76 (95% CI 1.39-2.23)], ever tested for HIV [AOR of 1.55 (95% CI 1.42-1.74)], visited health facility within the last 12 months [AOR of 1.26 (95% CI 1.12-1.41)] and decision-making autonomy [AOR of 1.42 (95% CI 1.27-1.60)] were positively associated with comprehensive HIV knowledge. However, being married [AOR of 0.72 (95% CI 0.62-0.82)] was negatively associated with comprehensive HIV knowledge. CONCLUSIONS: The prevalence of comprehensive HIV knowledge was low in Gambia. Educational interventions that focused mainly on awareness creation about HIV/AIDS should be designed especially for married women and lower socio-economic status. An effort has to be made to address those disparities at the national level.

Anti-PD-1 chimeric antigen receptor T cells efficiently target SIV-infected CD4+ T cells in germinal centers.

Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1+ memory T cells in blood and tissues, including lymph node CD4+ follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of CD8+ memory T cells. These data indicate anti-PD-1 CAR T cells depleted PD-1+ T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary.

Reported Unmet Hearing Aid Need in Older People With Dementia: The US National Core Indicators Survey.

OBJECTIVES: Hearing aids have important health benefits for older adults with Alzheimer disease and related dementias (ADRD); however, hearing aid adoption in this group is low. This study aimed to determine where to target hearing aid interventions for American long-term care recipients with ADRD by examining the association of ADRD and residence type with respondent-reported unmet hearing aid need. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the United States National Core Indicators-Aging and Disabilities survey (2015-2019) for long-term care recipients aged ≥65 years. METHODS: We used multivariable logistic regression to model the likelihood of reporting unmet hearing aid need conditional on ADRD status and residence type (own/family house or apartment, residential care, or nursing facility/home), adjusting for sociodemographic factors and response type (self vs proxy). RESULTS: Of the 25,492 respondents [median (IQR) age, 77 (71, 84) years; 7074 (27.8%) male], 5442 (21.4%) had ADRD and 3659 (14.4%) owned hearing aids. Residence types were 17,004 (66.8%) own/family house or apartment, 4966 (19.5%) residential care, and 3522 (13.8%) nursing home. Among non-hearing aid owners, ADRD [adjusted odds ratio (AOR) 0.90, 95% CI 0.80-1.0] and residence type were associated with respondent-reported unmet hearing aid need. Compared to the nursing home reference group, respondents in their own/family home (AOR 1.85, 95% CI 1.61-2.13) and residential care (AOR 1.30, 95% CI 1.10-1.53) were more likely to report unmet hearing aid need. This pattern was significantly more pronounced in people with ADRD than in those without, stemming from an interaction between ADRD and residence type. CONCLUSIONS AND IMPLICATIONS: American long-term care recipients with ADRD living in their own/family home are more likely to report unmet hearing aid need than those with ADRD in institutional and congregate settings. This information can inform the design and delivery of hearing interventions for older adults with ADRD.

Causal mediation analysis with mediator values below an assay limit.

Causal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the indirect effect through a mediator and the direct effect through all other pathways. A natural choice for a mediator in a randomized clinical trial is the treatment's targeted biomarker. However, when the mediator is a biomarker, values can be subject to an assay lower limit. The mediator is affected by the treatment and is a putative cause of the outcome, so the assay lower limit presents a compounded problem in mediation analysis. We propose two approaches to estimate indirect and direct effects with a mediator subject to an assay limit: (1) extrapolation and (2) numerical optimization and integration of the observed likelihood. Since these estimation methods solely rely on the so-called Mediation Formula, they apply to most approaches to causal mediation analysis: natural, separable, and organic indirect, and direct effects. A simulation study compares the two estimation approaches to imputing with half the assay limit. Using HIV interruption study data from the AIDS Clinical Trials Group described in Li et al 2016, AIDS; Lok and Bosch 2021, Epidemiology, we illustrate our methods by estimating the organic/pure indirect effect of a hypothetical HIV curative treatment on viral suppression mediated by two HIV persistence measures: cell-associated HIV-RNA and single-copy plasma HIV-RNA.

Preliminary testing of "roadmap to parenthood" decision aid and planning tool for family building after cancer: Results of a single-arm pilot study.

OBJECTIVE: Many young adult female cancer survivors need to use reproductive medicine, surrogacy, or adoption to have a child. This study pilot tested Roadmap to Parenthood, a web-based, self-guided decision aid and planning tool for family building after cancer (disease agnostic). METHODS: A single-arm pilot study tested feasibility, acceptability, and obtained effect size estimates of the Roadmap tool. Participants, recruited via hospital-based and social media strategies, completed a baseline survey (T1), accessed the Roadmap tool (website), then completed surveys at one- and 3-months (T2 and T3, respectively). Feasibility and acceptability were evaluated with rates of eligibility, enrollment, and survey completion, and feedback. Pairwise t-tests and repeated measures ANOVA evaluated usage effects. Effect size estimates were calculated. RESULTS: Participants (N = 98) averaged 31 years old (SD = 5.61); 71% were nulliparous. Enrollment rate was 73%, T1-T2 completion rate was 80%, and 93% accessed the website. From T1-T2, participants reported improvements in decisional conflict (p < 0.001; Cohen's d = 0.85), unmet information needs (p < 0.001; Cohen's d = 0.70), self-efficacy (p = 0.003; Cohen's d = 0.40), and self-efficacy for managing negative emotions (p = 0.03; Cohen's d = 0.29); effects were sustained at T3. There was no change in reproductive distress (p = 0.22). By T3, 94% reported increased consideration of preparatory actions and 20%-61% completed such actions. CONCLUSIONS: The Roadmap intervention was feasible to conduct, acceptable to users, and led to improvements in key psychosocial outcomes. Future directions will test intervention efficacy in a randomized controlled trial with a larger sample and over a longer period. A web-based tool may help women make decisions about family building after cancer and prepare for potential challenges.