Impact of Xpert MTB/RIF implementation in tuberculosis case detection and control in Brazil: a nationwide intervention time-series analysis (2011-2022).

Background: Since 2014, Brazil has gradually implemented the Xpert MTB/RIF (Xpert) test to enhance early tuberculosis (TB) and drug-resistant (DR-TB) detection and control, yet its nationwide impact remains underexplored. Our study conducts an intervention time-series analysis (ITSA) to evaluate how the Xpert's implementation has improved TB and DR-TB detection nationwide. Methods: 1,061,776 cases from Brazil's National TB Registry (2011-2022) were reviewed and ITSA (2011-2019) was used to gauge the impact of the Xpert's adoption on TB and DR-TB notification. Granger Causality and dynamic regression modelling determined if incorporating Xpert testing as an external regressor enhanced forecasting accuracy for Brazil's future TB trends. Findings: Xpert implementation resulted in a 9.7% increase in TB notification and substantial improvements in DR-TB (63.6%) and drug-susceptible TB (92.1%) detection compared to expected notifications if it had not been implemented. Xpert testing counts also presented a time-dependent relationship with DR-TB detection post-implementation, and improved predictions in forecasting models, which depicted a potential increase in TB and DR-TB detection in the next six years. Interpretation: This study underscores the critical role of Xpert's adoption in boosting TB and DR-TB detection in Brazil, reinforcing the case for its widespread use in disease control. Improvements in prediction accuracy resulting from integrating Xpert data are crucial for allocating resources and reducing the incidence of TB. By acknowledging Xpert's role in both disease control and improving predictions, we advocate for its expanded use and further research into advanced molecular diagnostics for effective TB and DR-TB control. Funding: FIOCRUZ.

Examining biopsychosocial predictors of risk for cognitive impairment among a racially diverse sample of men who have sex with men living with HIV.

Background: Cognitive decline among people living with HIV (PLWH) is growing concern as world populations become increasing older including higher proportions of PLWH. It is vitally important to understand psychosocial predictors of age-related cognitive decline men who have sex with men (MSM) living with HIV. Objectives: The current study seeks to examine psychosocial risk factors the contribute to the risk of age-related cognitive impairment as measured by Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in a racially diverse sample of MSM living with HIV. Design: The present analysis utilizes data from the baseline (n = 196) and 6-month follow-up (n = 135) time points of a longitudinal cohort study of PLWH. Methods: Using a self-report survey, we examine the associations between psychosocial predictors (e.g. trauma, mental health, chronic pain, sleep disturbance, etc.) and risk of dementia using the CAIDE risk score. Analyses include linear and logistic regression. Results: In adjusted model stress, chronic pain, Black racial identity, and having a sexual identity that is bisexual or another category are all positively associated with CAIDE scores. Childhood sexual abuse history was negatively associated with CAIDE scores indicating a protective effect. Sleep disorder has a positive association with CAIDE scores after adjusting for the baseline CAIDE scores. Conclusion: These results indicate modifiable correlates of cognitive risk (stress and chronic pain). Interventions should seek to address these comorbid factors including the consideration of minority stress and stigma. Interventions should seek to reach Black and bisexual men living with HIV, including possible cultural tailoring to interventions and messaging. Lastly, future research should examine the impact of variation within childhood sexual abuse histories to better understand their association with cognitive impairment later in life. This may include considering the nature, severity, and potential treatment of trauma symptoms.

What makes middle-aged or older people who have HIV more likely to have memory problems later in life? We asked a racially diverse group of gay and bisexual men who have HIV. Why was the study done? Older people are becoming a larger portion of our communities including older people living with HIV. It's important to understand what makes older people more likely to have memory problems as they age including older people living with HIV. What did the researchers do? We asked 196 middle-aged and older adults who have HIV to answer questions about their health including things that we know might make them more likely to have memory problems later in life. What did the researchers find? We found that having more stress or reoccurring pain was related to being more likely to have memory problems later in life. People who have trouble sleeping were more likely to have memory problems later in life. We also found that Black people were more likely to have memory problems later in life. People who had been abused sexually as children were less likely to have memory problems later in life. What do the findings mean? These findings help us understand things that may make someone more likely to have memory problems later in life. These include things that could be changed like reoccurring pain and troubles sleeping. It also highlighted that Black people may need more support to prevent memory problems later in life.

Inflammatory profiles in sputum and blood of people with TB with and without HIV coinfection.

Although tuberculosis (TB) remains a major killer among infectious diseases and the leading cause of death for people with HIV, drivers of immunopathology, particularly at the site of infection in the lungs remain incompletely understood. To fill this gap, we compared cytokine profiles in paired plasma and sputum samples collected from adults with pulmonary TB with and without HIV. We found that people with pulmonary TB with HIV had significantly higher markers of inflammation in both plasma and sputum than those without HIV; these differences were present despite a similar extent of radiographic involvement. We also found that the strength and direction of correlations between biomarkers in the blood and lung compartments differed by HIV status and people with HIV had more positive correlations than those without HIV. Future studies can further explore these differences in inflammation by HIV status across the blood and lung compartments and seek to establish how these profiles may be associated with long-term outcomes and lung health after completion of TB treatment.

Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions.

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

Machine learning algorithms using national registry data to predict loss to follow-up during tuberculosis treatment.

BACKGROUND: Identifying patients at increased risk of loss to follow-up (LTFU) is key to developing strategies to optimize the clinical management of tuberculosis (TB). The use of national registry data in prediction models may be a useful tool to inform healthcare workers about risk of LTFU. Here we developed a score to predict the risk of LTFU during anti-TB treatment (ATT) in a nationwide cohort of cases using clinical data reported to the Brazilian Notifiable Disease Information System (SINAN). METHODS: We performed a retrospective study of all TB cases reported to SINAN between 2015 and 2022; excluding children (< 18 years-old), vulnerable groups or drug-resistant TB. For the score, data before treatment initiation were used. We trained and internally validated three different prediction scoring systems, based on Logistic Regression, Random Forest, and Light Gradient Boosting. Before applying our models we splitted our data into training (~ 80% data) and test (~ 20%) sets, and then compared the model metrics using the test data set. RESULTS: Of the 243,726 cases included, 41,373 experienced LTFU whereas 202,353 were successfully treated. The groups were different with regards to several clinical and sociodemographic characteristics. The directly observed treatment (DOT) was unbalanced between the groups with lower prevalence in those who were LTFU. Three models were developed to predict LTFU using 8 features (prior TB, drug use, age, sex, HIV infection and schooling level) with different score composition approaches. Those prediction scoring systems exhibited an area under the curve (AUC) ranging between 0.71 and 0.72. The Light Gradient Boosting technique resulted in the best prediction performance, weighting specificity and sensitivity. A user-friendly web calculator app was developed ( https://tbprediction.herokuapp.com/ ) to facilitate implementation. CONCLUSIONS: Our nationwide risk score predicts the risk of LTFU during ATT in Brazilian adults prior to treatment commencement utilizing schooling level, sex, age, prior TB status, and substance use (drug, alcohol, and/or tobacco). This is a potential tool to assist in decision-making strategies to guide resource allocation, DOT indications, and improve TB treatment adherence.

Improving Delivery and Use of HIV Pre-Exposure Prophylaxis in the US: A Systematic Review of Implementation Strategies and Adjunctive Interventions.

Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States. To date, the literature has focused on identifying determinants of PrEP use, with a lesser focus on developing and testing change methods to improve PrEP implementation. Moreover, the change methods available for improving the uptake and sustained use of PrEP have not been systematically categorized. To summarize the state of the literature, we conducted a systematic review of the implementation strategies used to improve PrEP implementation among delivery systems and providers, as well as the adjunctive interventions used to improve the uptake and persistent adherence to PrEP among patients. Between November 2020 and January 2021, we searched Ovid MEDLINE, PsycINFO, and Web of Science for peer reviewed articles. We identified 44 change methods (18 implementation strategies and 26 adjunctive interventions) across a variety of clinical and community-based service settings. We coded implementation strategies and adjunctive interventions in accordance with established taxonomies and reporting guidelines. Most studies focused on improving patient adherence to PrEP and most conducted pilot trials. Just over one-third of included studies demonstrated a positive effect on outcomes. In order to end the human immunodeficiency virus (HIV) epidemic in the U.S., future, large scale HIV prevention research is needed that develops and evaluates implementation strategies and adjunctive interventions for target populations disproportionately affected by HIV.

High-throughput prioritization of target proteins for development of new antileishmanial compounds.

Leishmaniasis, a vector-borne disease, is caused by the infection of Leishmania spp., obligate intracellular protozoan parasites. Presently, human vaccines are unavailable, and the primary treatment relies heavily on systemic drugs, often presenting with suboptimal formulations and substantial toxicity, making new drugs a high priority for LMIC countries burdened by the disease, but a low priority in the agenda of most pharmaceutical companies due to unattractive profit margins. New ways to accelerate the discovery of new, or the repositioning of existing drugs, are needed. To address this challenge, our study aimed to identify potential protein targets shared among clinically-relevant Leishmania species. We employed a subtractive proteomics and comparative genomics approach, integrating high-throughput multi-omics data to classify these targets based on different druggability metrics. This effort resulted in the ranking of 6502 ortholog groups of protein targets across 14 pathogenic Leishmania species. Among the top 20 highly ranked groups, metabolic processes known to be attractive drug targets, including the ubiquitination pathway, aminoacyl-tRNA synthetases, and purine synthesis, were rediscovered. Additionally, we unveiled novel promising targets such as the nicotinate phosphoribosyltransferase enzyme and dihydrolipoamide succinyltransferases. These groups exhibited appealing druggability features, including less than 40% sequence identity to the human host proteome, predicted essentiality, structural classification as highly druggable or druggable, and expression levels above the 50th percentile in the amastigote form. The resources presented in this work also represent a comprehensive collection of integrated data regarding trypanosomatid biology.

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNFα and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.

The impact of ZIKV infection on gene expression in neural cells over time.

Zika virus (ZIKV) outbreak caused one of the most significant medical emergencies in the Americas due to associated microcephaly in newborns. To evaluate the impact of ZIKV infection on neuronal cells over time, we retrieved gene expression data from several ZIKV-infected samples obtained at different time point post-infection (pi). Differential gene expression analysis was applied at each time point, with more differentially expressed genes (DEG) identified at 72h pi. There were 5 DEGs (PLA2G2F, TMEM71, PKD1L2, UBD, and TNFAIP3 genes) across all timepoints, which clearly distinguished between infected and healthy samples. The highest expression levels of all five genes were identified at 72h pi. Taken together, our results indicate that ZIKV infection greatly impacts human neural cells at early times of infection, with peak perturbation observed at 72h pi. Our analysis revealed that all five DEGs, in samples of ZIKV-infected human neural stem cells, remained highly upregulated across the timepoints evaluated. Moreover, despite the pronounced inflammatory host response observed throughout infection, the impact of ZIKV is variable over time. Finally, the five DEGs identified herein play prominent roles in infection, and could serve to guide future investigations into virus-host interaction, as well as constitute targets for therapeutic drug development.

An integrative multi-omics approach to characterize interactions between tuberculosis and diabetes mellitus.

Tuberculosis-diabetes mellitus (TB-DM) is linked to a distinct inflammatory profile, which can be assessed using multi-omics analyses. Here, a machine learning algorithm was applied to multi-platform data, including cytokines and gene expression in peripheral blood and eicosanoids in urine, in a Brazilian multi-center TB cohort. There were four clinical groups: TB-DM(n = 24), TB only(n = 28), DM(HbA1c ≥ 6.5%) only(n = 11), and a control group of close TB contacts who did not have TB or DM(n = 13). After cross-validation, baseline expression or abundance of MMP-28, LTE-4, 11-dTxB2, PGDM, FBXO6, SECTM1, and LINCO2009 differentiated the four patient groups. A distinct multi-omic-derived, dimensionally reduced, signature was associated with TB, regardless of glycemic status. SECTM1 and FBXO6 mRNA levels were positively correlated with sputum acid-fast bacilli grade in TB-DM. Values of the biomarkers decreased during the course of anti-TB therapy. Our study identified several markers associated with the pathophysiology of TB-DM that could be evaluated in future mechanistic investigations.

The sound of silent RNA in tuberculosis and the lncRNA role on infection.

Tuberculosis (TB) is one of the leading causes of death worldwide, and Diabetes Mellitus is one of the major comorbidities (TB/DM) associated with the disease. A total of 103 differentially expressed ncRNAs have been identified in the TB and TB/DM comparisons. A machine learning algorithm was employed to identify the most informative lncRNAs: ADM-DT, LINC02009, LINC02471, SOX2-OT, and GK-AS1. These lncRNAs presented substantial accuracy in classifying TB from HC (AUCs >0.85) and TB/DM from HC (AUCs >0.90) in the other three countries. Genes with significant correlations with the five lncRNAs enriched common pathways in Brazil and India for both TB and TB/DM. This suggests that lncRNAs play an important role in the regulation of genes related to the TB immune response.

BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility.

Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1-/- macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1-/- mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection.

Factors Associated with HIV Testing Among Spanish and English-Speaking Latino Adolescents Aged 13-18.

Adolescent Latino men who have sex with men (LMSM) in the U.S. are disproportionately impacted by HIV. However, there has been limited focus on their HIV prevention and risk behaviors. In this study, we examine the rates of HIV testing and explore the significant demographic and healthcare factors that influence HIV prevention among adolescent LMSM. The analysis for this study utilized data collected during the baseline assessment of SMART, a pragmatic trial aimed at evaluating the effectiveness of an online HIV prevention intervention for adolescent LMSM (N = 524). Only 35.5% of participants had ever had an HIV test in their lifetime. Rates of testing increased among adolescent LMSM who had a doctor with whom they spoke about their sexual health (odds ratio: 4.0; 95% confidence interval: 2.1-8.4; P < 0.001) or HIV testing (odds ratio: 5.8; 95% confidence interval: 3.1-10.7; P < 0.001). Out of the 61 participants who took part in the survey conducted in Spanish, only 26% reported ever having an HIV test. Additionally, 24.5% stated that they had discussed their sexual orientation with a doctor, and only 8.2% had undergone HIV testing. Spanish-speaking adolescents who completed the SMART survey were less likely to openly discuss their sexual orientation or sexual health with most people or have a doctor with whom they discussed these topics, compared to those who completed the survey in English. These findings suggest that Spanish-speaking adolescent LMSM may face obstacles in accessing HIV prevention services in the U.S.

RESUMEN: Los adolescentes latinos hombres que tienen sexo con otros hombres (LHSH) tienen mayor probabilidad de recibir tratamiento para el VIH más tarde en comparación con todos los casos nuevos del VIH en los Estados Unidos. Sin embargo, se ha estudiado muy poco sus prácticas de prevención de VIH o prácticas de riesgo, que similar a la de jóvenes no latinos, es determinada por múltiples factores. En este estudio describimos las tasas de pruebas para el VIH e identificamos los factores lingüísticos, individuales, familiares, escolares y de cuidado de salud que influencian a los adolescentes LHSH. Los datos provinieron de la evaluación inicial para SMART, un ensayo práctico de una intervención en línea para prevenir el VIH entre adolescentes LHSH (N = 524). Las medidas incluían la experiencia de hacerse la prueba del VIH a lo largo de la vida, factores de aculturación, datos demográficos, prácticas sexuales, educación sobre el VIH en la escuela y el hogar, comunicación sobre salud sexual con los médicos, conocimiento sobre el VIH y actitudes de riesgo. Solo 35.5% de los participantes se han realizado la prueba de VIH al menos una vez en su vida. La tasa de pruebas del VIH fue más alta entre los adolescentes LHSH que indicaron haber hablado con su médico sobre su salud sexual (odds ratio: 4.0; intervalo de confianza del 95%: 2.1­8.4; P < 0.001) o de la prueba del VIH (odds ratio: 5.8; intervalo de confianza del 95%: 3.1­10.7; P < 0.001). Más de 60 participantes completaron la encuesta en español. De estos, pocos reportaron alguna vez haberse hecho la prueba del HIV (26%), tener un médico con quien hablar sobre su orientación sexual (24.5%) o hablar sobre la prueba del VIH (8.2%). Estas cifras son significativamente más bajas que las obtenidas en la encuesta en inglés. Este estudio es uno de los primeros en evaluar los factores para hacerse la prueba del VIH entre adolescentes latinos que hablan inglés y español con edades entre 13 y 18 años. Los adolescentes latinos que completaron SMART en español tuvieron menos probabilidad de haber compartido sobre su orientación sexual con la mayoría de las personas o tener un médico con quien hablar sobre su orientación sexual o su salud sexual, en comparación con aquellos que completaron SMART en inglés, lo que sugiere que los jóvenes latinos que prefieren comunicarse en español pueden experimentar mayores barreras para acceder a los servicios de prevención del VIH en los Estados Unidos.

A Systematic Review of Implementation Research on Determinants and Strategies of Effective HIV Interventions for Men Who Have Sex with Men in the United States.

Men who have sex with men (MSM) are disproportionately affected by HIV, accounting for two-thirds of HIV cases in the United States despite representing ∼5% of the adult population. Delivery and use of existing and highly effective HIV prevention and treatment strategies remain suboptimal among MSM. To summarize the state of the science, we systematically review implementation determinants and strategies of HIV-related health interventions using implementation science frameworks. Research on implementation barriers has focused predominantly on characteristics of individual recipients (e.g., ethnicity, age, drug use) and less so on deliverers (e.g., nurses, physicians), with little focus on system-level factors. Similarly, most strategies target recipients to influence their uptake and adherence, rather than improving and supporting implementation systems. HIV implementation research is burgeoning; future research is needed to broaden the examination of barriers at the provider and system levels, as well as expand knowledge on how to match strategies to barriers-particularly to address stigma. Collaboration and coordination among federal, state, and local public health agencies; community-based organizations; health care providers; and scientists are important for successful implementation of HIV-related health innovations.

Acceptability of 'Humpr': An Online Tool to Educate Adolescent Sexual Minority Males About Sexual Networking Applications.

We examined the acceptability of Humpr - an interactive, online tool developed to educate adolescent sexual minority males (ASMM) about how to safely navigate sexual networking applications (SNA). We developed Humpr as part of a larger HIV intervention trial in the U.S. In Humpr, 218 ASMM aged 14-20 (Mage = 17.18) created a mock dating profile, explored simulated user profiles, learned health-related information (e.g. slang indicating HIV/STI risks and/or drug use intentions), and then gave feedback regarding acceptability of the tool. Results showed that Humpr was very well-received, with 94% overall approval rates. Reasons for liking Humpr were evenly split between liking it for educational and entertaining reasons. Participants praised Humpr for its realistic design and interactive interface that allowed them to engage and connect with the tool. The majority (61%) had used SNAs in the past, but many still reported learning something new from Humpr. Participants also appreciated the acknowledgment of SNA use in ASMM and how the education was implemented in an open and judgment-free way. Topics learned from Humpr included how to be safe on SNAs and warning signs for HIV/STI risks. Suggested areas of improvement included having an opt-out option for those who do not wish to participate for any reason (e.g. discomfort) and additional educational content (e.g. consequences of being a minor on SNAs). Taken together, the findings offer preliminary evidence for the potential educational benefits of digital tools like Humpr for ASMM with and without prior SNA exposure.

Another tick bites the dust: exploring the association of microbial composition with a broad transmission competence of tick vector species.

IMPORTANCE: Some tick species are competent to transmit more than one pathogen while other species are, until now, known to be competent to transmit only one single or any pathogen. Such a difference in vector competence for one or more pathogens might be related to the microbiome, and understanding what differentiates these two groups of ticks could help us control several diseases aiming at the bacteria groups that contribute to such a broad vector competence. Using 16S rRNA from tick species that could be classified into these groups, genera such as Rickettsia and Staphylococcus seemed to be associated with such a broad vector competence. Our results highlight differences in tick species when they are divided based on the number of pathogens they are competent to transmit. These findings are the first step into understanding the relationship between one single tick species and the pathogens it transmits.

Identification of Determinants and Implementation Strategies to Increase Long-Acting Injectable PrEP for HIV Prevention Among Latino Men Who Have Sex with Men (MSM).

BACKGROUND: Latino men who have sex with men (LMSM) are disproportionally affected by HIV infections in the USA. The uptake rate of pre-exposure prophylaxis (PrEP) for HIV prevention has remained low among LMSM. Long-acting injectable PrEP (LAI-PrEP) may have the potential to improve structural, behavioral, and cognitive barriers to adherence. Given the potential benefits of LAI-PrEP and the limited data with this population, the aim of our study was to explore experiences and attitudes of LAI-PrEP among LMSM and identify implementation barriers compared to the standard oral presentation, align proposed implementation strategies, and propose outcomes to monitor and assess impact. METHODS: In this qualitative study, guided by the Consolidated Framework for Implementation Research, we explored health care providers perspectives on facilitators and barriers to LAI-PrEP implementation strategies for LMSM. Interviews were recorded, transcribed, and analyzed using thematic content analysis. RESULTS: Fear of immigration policies, ability to conceal PrEP medication, health insurance coverage, health information fatigue, lack of culturally adapted information, and provider's lack of knowledge were among the main barriers to LAI-PrEP. Most providers discussed the need for adapted and/or tailored training materials for and suggested designing marketing materials and specific clinical recommendations for LAI-PrEP. CONCLUSION: In order to ensure an effective adaptation process that encompasses local and national goals of HIV prevention, future interventions should be designed in a way that incorporates culturally relevant information for LMSM. This study provides an implementation research logic model to guide future studies.

A multi-center, prospective cohort study of whole blood gene expression in the tuberculosis-diabetes interaction.

Diabetes mellitus (DM) increases tuberculosis (TB) severity. We compared blood gene expression in adults with pulmonary TB, with or without diabetes mellitus (DM) from sites in Brazil and India. RNA sequencing (RNAseq) performed at baseline and during TB treatment. Publicly available baseline RNAseq data from South Africa and Romania reported by the TANDEM Consortium were also analyzed. Across the sites, differentially expressed genes varied for each condition (DM, TB, and TBDM) and no pattern classified any one group across all sites. A concise signature of TB disease was identified but this was expressed equally in TB and TBDM. Pathway enrichment analysis failed to distinguish TB from TBDM, although there was a trend for greater neutrophil and innate immune pathway activation in TBDM participants. Pathways associated with insulin resistance, metabolic dysfunction, diabetic complications, and chromosomal instability were positively correlated with glycohemoglobin. The immune response to pulmonary TB as reflected by whole blood gene expression is substantially similar with or without comorbid DM. Gene expression pathways associated with the microvascular and macrovascular complications of DM are upregulated during TB, supporting a syndemic interaction between these coprevalent diseases.

The impact of the COVID-19 pandemic on mental health, associated factors and coping strategies in people living with HIV: a scoping review.

INTRODUCTION: The COVID-19 pandemic and associated measures implemented by authorities have created additional stressors and increased the risk of psychological illnesses among people living with HIV (PLWH). Yet, there is no collective evidence on the mental health status of this population during the global pandemic and associated factors. This scoping review aimed to synthesize the evidence in the current literature related to the mental health outcomes and challenges faced by PLWH during the COVID-19 pandemic, identify the associated factors with psychological distress and summarize various coping strategies to ease these psychological distresses used by this population. METHODS: We conducted a scoping review following the PRISMA-ScR guideline and a literature search in four electronic databases in August 2022. Three reviewers independently screened all the search records and extracted the data from studies that met the inclusion criteria. Factors associated with worsened mental health outcomes were synthesized according to the socio-ecological framework. RESULTS: Among 1100 research records, 45 articles met the eligibility criteria and were included in the final review and data extraction, most of which were quantitative analyses. PLWH reported high rates of mental health problems during the pandemic. Multi-level factors were associated with increased psychological distress, including substance use, antiretroviral adherence, social support, financial hardship and economic vulnerability during the pandemic. PLWH used social media as a coping strategy to foster social support to deal with growing mental distress. Increased mental health illnesses were associated with increased substance use, it was also found associated with suboptimal medication adherence and antiretroviral therapy (ART) care engagement. DISCUSSION: PLWH experienced high rates of mental health illnesses, such as depression during the global COVID-19 pandemic. There is an urgent need to provide comprehensive HIV treatment and mental health services as the pandemic continues to evolve. CONCLUSIONS: The review summarized how the mental health of PLWH was affected during the COVID-19 pandemic. Future work in the implementation of effective interventions to promote mental health in this population is needed, not only to ensure their quality of life but also to help them maintain ART adherence and healthcare during more unprecedented times.

Categorising implementation determinants and strategies within the US HIV implementation literature: a systematic review protocol.

INTRODUCTION: Despite decreased rates of new infections, HIV/AIDS continues to impact certain US populations. In order to achieve the goals laid out in the Ending the HIV Epidemic (EHE) in the US initiative, implementation science is needed to expand the sustained use of effective prevention and treatment interventions, particularly among priority populations at risk for and living with HIV/AIDS. Over 200 HIV-related implementation studies have been funded by the US National Institutes of Health. Therefore, a comprehensive review of the literature identifying implementation determinants (barriers and facilitators) and categorising implementation strategies across the continuum of HIV prevention and care in the USA is appropriate and needed to enhance current knowledge and help achieve the goals laid out in the EHE national strategic plan. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Between November 2020 and January 2022, a broad database search strategy of Ovid MEDLINE, PsycINFO and Web of Science was conducted to capture implementation-related studies along the HIV prevention and care continuum. Articles were eligible for inclusion if they were: conducted in the USA, published after the year 2000, written in English, related to HIV/AIDS, focused on outcomes related to dissemination and implementation (ie, did not test/evaluate/explore implementation determinants or strategies) and were behavioural studies (ie, not basic science). We plan to conduct three systematic reviews to identify and categorise determinants and strategies associated with three HIV focus areas: pre-exposure prophylaxis, testing/diagnosing and linkage to care, and treatment. Determinants will be coded according to an adapted Consolidated Framework for Implementation Research 2.0. Implementation strategies and outcomes will be categorised in accordance with existing taxonomies and frameworks. ETHICS AND DISSEMINATION: Ethics approval is not applicable. No original data will be collected. Results will be disseminated through peer-reviewed publications, conference presentations and via online tools. PROSPERO REGISTRATION NUMBER: CRD42021233089.