Approximately 80% of all breast cancer cases are estrogen receptor-positive (ER+). This subtype is known to have distant recurrences in a subset of patients after adjuvant endocrine therapy, partially due to the heterogeneity of the disease. ER+ breast cancer has been generally classified as an immune-cold disease. Thus, to better inform treatment decisions and to consider the prospect of immunotherapy, the immune microenvironment needs to be thoroughly characterized. In this study, the proteome and transcriptome of the tumour and tumour microenvironment (TME) were characterized using the GeoMx Digital Spatial Profiler (DSP) and NanoString’s BC360 gene expression panel. Spatially resolved tumour and TME across a patient's lumpectomy demonstrated substantial heterogeneity in the expression of commonly targeted immune and tumour proteins. Results from this study demonstrated heterogeneity across the tumour and TME in ER+ breast cancer, which may be reflective of a variable immune response.
Background Hypertension is a leading contributor to cardiovascular disease morbidity among people with HIV (PWH), yet adherence to antihypertensive medications remains suboptimal. While HIV care has achieved high levels of medication adherence through structured monitoring and communication, less is known about how PWH and HIV providers perceive barriers and possible interventions to antihypertensive adherence within HIV care settings. Methods Semi-structured interviews were conducted with 20 virally suppressed PWH diagnosed with hypertension and 19 HIV providers between August 2022 and February 2024. Interviews explored experiences and perceptions related to antihypertensive medication adherence. Data were analyzed using a rapid qualitative approach with matrix-based techniques and mapped to the Capability, Opportunity, and Motivation (COM-B) behavior change framework. Results PWH and HIV providers identified overlapping barriers to antihypertensive adherence spanning all COM-B domains. Shared motivational barriers included concerns about side effects, pill burden, and low perceived urgency of hypertension. Opportunity-related barriers included competing life demands and limited visibility of nonadherence due to blood pressure variability. Capability-related challenges centered on difficulty communicating and understanding long-term hypertension risk compared with HIV. Divergence of perspectives emerged around communication, with PWH frequently describing misunderstandings about instructions and intentional non-disclosure of nonadherence, whereas HIV providers emphasized limited capacity to manage non-HIV conditions. Conclusions Antihypertensive medication nonadherence among PWH reflects patient-, provider-, and system-level challenges that are not fully addressed within HIV care. Extending the strengths of HIV care through structured communication, monitoring, and care delivery offers a practical pathway to improving cardiovascular outcomes among PWH.
People living with HIV (PLHIV) are at an increased risk of oral manifestations, including those linked to human papillomavirus (HPV). In Tanzania, the prevalence and impact of oral HPV among PLHIV remain unknown. This scoping review aimed to map evidence and identify gaps at the intersection of HIV, HPV, and oral health. We conducted a scoping review of studies on oral health in relation to HIV or HPV. Studies involving HPV or oral health among PLHIV were included, while studies conducted outside Tanzania, lacked empirical data, or did not report relevant outcomes were excluded. Outcomes were prevalence of oral manifestations, HPV detection, HPV vaccination, and intervention effectiveness. Forty-four studies were included. One assessed HPV and oral health; none evaluated HPV vaccination effects on oral outcomes. Prevalence of oral manifestations among PLHIV increased from 10
People living with HIV/AIDS (PLWHA) are more likely to experience significant generalized anxiety symptoms compared to the general population, which require both pharmacological and psychological treatment. There is limited evidence on the specific facilitators and barriers to treatment-seeking behaviours for significant generalized anxiety symptoms among PLWHA in Kilimanjaro region. This study aims to determine facilitators and barriers to treatment-seeking behaviours for significant generalized anxiety symptoms among PLWHA in Kilimanjaro region. This exploratory pilot study employed a qualitative design to assess facilitators and barriers to treatment-seeking for generalized anxiety symptoms among PLWHA in Kilimanjaro region and used the Generalized Anxiety Disorder-7 (GAD-7) screener to identify significant generalized anxiety symptoms in adult PLWHA who were followed up for three months. Thematic framework analysis was employed to identify and interpret patterns in treatment-seeking behaviors. Among 348 PLWHA, only 8.6% (30 PLWHA) had screened positive for significant generalized anxiety symptoms. Among 30 with significant anxiety symptoms, 6 (20%) PLWHA attended mental health services, 15 (50%) PLWHA did not attend, and 9 (30%) PLWHA were lost to follow-up. Facilitators identified were having mental health awareness, support from family and friends, and having good customer service in mental health clinics. Economic burdens, few mental health services, and stigma were potential barriers to treatment seeking for significant generalized anxiety symptoms. Addressing both facilitators and barriers to treatment-seeking for significant generalized anxiety symptoms among PLWHA, including increasing awareness, reducing stigma, improving access to services, and providing strong social support, is essential for enhancing mental health care.
INTRODUCTION:HIV poses a significant global health concern, affecting adolescents among other populations. This is attributed to various vulnerabilities including biological factors, gender inequalities and limited access to comprehensive sexual and reproductive health services in sub-Saharan Africa. In Tanzania, adolescent girls, and young women (AGYW) face double the risk of HIV infection compared to their male counterparts. The introduction of pre-exposure prophylaxis (PrEP) in early 2018 brought hope for changing the HIV cascade in the country. However, numerous challenges still hinder PrEP uptake. Therefore, this study explored experiences of PrEP uptake among vulnerable AGYW in Tanzania. METHODS:This study employed a phenomenological qualitative approach; 52 semi-structured interviews were carried out between May to November 2022 in the selected healthcare facilities in Tanzania. The study adopted inductive-deductive thematic analysis guided by the Social Ecological Model (SEM) to elicit the views of AGYW aged 15-24. Nvivo software was utilised to organise data. RESULTS:This study has uplifted barriers and facilitators on PrEP uptake among AGYW in Tanzania. The barriers are categorized at individual, interpersonal, and institutional levels. The individual level barriers included pre-requisites for initiating PrEP, disbelief in the effectiveness of PrEP, interference of refill hours with working hours, financial constraints, and adherence to the pills. The interpersonal level barriers included misconceptions about PrEP pills, and labelling of PrEP users. The institutional level barriers included inadequate privacy, PrEP drug stockout, being turned away by health care facilities (HCF), long waiting times, and distance to the HCF. Facilitators included factors at individual level (experienced benefit of PrEP, adequate PrEP knowledge, having multiple partners, perceived risk due to the nature of the work, PrEP ensuring privacy), interpersonal level (support from social networks), and institutional level (Free availability of PrEP, receiving refill reminders). CONCLUSIONS:To overcome barriers to PrEP uptake among AGYW, it is crucial to develop multi-level interventions that consider personal, social, and structural factors hindering PrEP uptake. Implementing strategies like prioritizing off-site PrEP delivery and expanding community outreach for PrEP awareness can help dispel misconceptions and enhance uptake.
Background:The burden of cancer in sub-Saharan African countries is escalating with a rising Human Immunodeficiency Virus (HIV) prevalence. However, information about the burden of HIV on cancer epidemiology is scarce. Specifically, little is known about HIV infection among the cancer cases registered in the Kilimanjaro Population Cancer Registry (KCR) despite the presence of this infection in Tanzania. Thus, our study aimed to assess the burden of HIV in cancer patients by evaluating HIV serostatus information among recorded cases of malignancies in the KCR. Methods:This secondary data analysis examined records of all cancer cases registered in the KCR from January 2018 through December 2022 to assess the status of HIV infection among the cancer cases. Variables assessed were demographic information, type of cancer, and HIV serostatus. Proportions were analyzed using descriptive data. Results:A total of 5,508 cancer cases were recorded from 2018 through 2022. HIV serostatus was documented in 4.8% (226/5,508) of the cancer cases, 68% of which were HIV seropositive with a slight female predominance (male-to-female ratio of 1:1.7). Cervical cancer was the leading malignancy (18%) with recorded HIV serostatus. Patients aged 18-50 years and females had the highest prevalence of HIV infection (64.6% and 63.5%). Conclusion:HIV infection is still underreported among cancer patients in the cancer registry of the Kilimanjaro region with only 4.8% of malignancies registered in KCR having a documented HIV serostatus. HIV serostatus was mostly documented in AIDS-defining cancers. Thus, efforts to support HIV counseling and testing among cancer patients should be made, as this will also affect treatment plans and monitoring.
Background Mothers attending prevention of mother-to-child transmission (PMTCT) of HIV clinics seem to lack knowledge on many aspects of PMTCT, among which is breastfeeding. Breastfeeding recommendations in PMTCT have changed several times over the years leaving some confused and doubtful of what is currently recommended. One method shown to help improve their knowledge and acceptance of PMTCT recommendations is the use of peer educators. We sought to determine if mothers engage in discussions with other mothers during clinics and how these engagements influence trust in PMTCT recommendations. Methods We interviewed 524 mothers with children under two years enrolled in PMTCT clinics in Kilimanjaro, Tanzania. We selected 5 clinics with the highest numbers of PMTCT enrolment from each district in the region. In each clinic, over a one-month period, we recruited all mothers attending the PMTCT clinic. We collected information on their engagement in discussions regarding PMTCT during clinics and how they perceived the information from their peers in relation to that from healthcare providers. Results Fifty-five percent of the mothers reported engaging in peer discussions. Of the 90 (17%) mothers who reported noticing a change in PMTCT recommendations, 33 (36.7%) reported trusting previous recommendations more. A greater proportion (52.9%) of mothers who engaged in peer discussions reported trusting the information from peers more than that from healthcare workers. Conclusions Peers have a great influence on mothers, which is concerning when their knowledge shared is outdated. Harnessing their influence and training them on current recommendations might be key to improving adherence to PMTCT recommendations.
Abstract While the use of CDK4/6 inhibitors has significantly improved outcomes for patients with ER+/HER2- tumours, understanding the mechanisms responsible for resistance is essential to identify predictive biomarkers and alternative treatment options after tumour progression. To this end, we developed in-vitro models of acquired resistance to palbociclib and abemaciclib using MCF7 and T47D cell lines. Genomic, transcriptomic, and proteomic analyses were used to identify potential actionable molecular alterations in these models. Results show that acquired resistance was associated with dysregulation of multiple signaling pathways, including cyclin D-CDK4/6-RB, EGFR/HER and AKT/mTORC1. Strikingly, acquired resistance across all cell lines was also associated with an upregulated interferon (IFN) response. Expression of an IFN-based gene signature derived from these models was upregulated in breast cancer cell lines and early-stage tumours intrinsically resistant to CDK4/6i, and thus warrants further clinical evaluation as a predictive biomarker of resistance.
Background HIV partner counselling and testing in antenatal care (ANC) is a crucial strategy to raise the number of males who know their HIV status. However, in many settings like Tanzania, male involvement in antenatal care remains low, and there is a definite need for innovative strategies to increase male partner involvement. This study was designed to evaluate the efficacy of mobile phone intervention increase male partner ANC attendance for HIV testing in Moshi municipal, Tanzania.Methods Between April and July 2022, we enrolled pregnant women presenting to a first ANC visit at Majengo and St. Joseph reproductive health facilities without their male partners. Eligible pregnant women were randomly assigned to invitation of their male partners either via phone calls, text messages from clinic staff and verbal invites from pregnant partners (intervention arm) or verbal invites only from the pregnant partners (control arm). Neither healthcare provider nor participant were blinded. The primary outcome was the proportion of male partners who attended ANC with their pregnant partners during a follow-up period of two consecutive visits. The secondary outcome measure was HIV testing among male partners following the invitation. Participants were analyzed as originally assigned (intention to treat).Results A total of 350 pregnant women presenting to ANC for the first time were enrolled, with 175 women enrolled in each arm. The efficacy of male attendance with their pregnant women following the invitations was 83.4% (147/175) in the intervention arm and 46.3% (81/175) in the control arm. Overall, the results suggest a positive and statistically significant average treatment effect among men who received mobile phone intervention on ANC attendance. For the secondary outcome, the percent of male partners who accepted HIV counselling and testing was 99.3% (146/147) in the intervention arm and 93.8% (76/81) in the control arm. Married men were having higher odds of ANC attendance compared with single men (aOR:6.40(3.26-12.56), Males with multigravida women were having lower odds of ANC attendance compared with primigravida women (aOR:0.17(0.09-0.33).Conclusion The study demonstrates that supplementing verbal invitations with mobile phone calls and text messages from clinic staff can significantly increase male partner ANC attendance and HIV testing. This combined approach is recommended in improving ANC attendance and HIV testing of male partners who do not accompany their pregnant partners to antenatal clinics in the first visits.Trial registration PACTR202209769991162.
Abstract Background: Larger tumors pose an increased risk for breast cancer (BC) recurrence post-surgery. In addition, most BC outside of the triple negative subtype are considered immunological quiescent and minimally responsive to immunotherapies. One potential method to combat disease recurrence risk and induce immune activation pre-surgery is through a local therapy that could cause cell death to expose tumor antigens, provide adjuvants for anti-tumor immune priming, and thus potentially increase responsiveness to immunotherapies or rates of pathological complete response in combination with chemotherapy. We have conducted a randomized, Phase 2 presurgical Window-Of-Opportunity trial for intratumoral (IT) INT230-6 comprising vinblastine, cisplatin and a diffusion enhancer (SHAO) in patients with early-stage operable BC, the INVINCIBLE trial (NCT04781725). Previous in vivo and clinical studies demonstrated that INT230-6 induces cancer cell death and halts replication while maturing dendritic cells and recruiting T-cells into the tumor. In this trial, IT injections of INT230-6 were conducted to 1) evaluate the safety of regional cytotoxic use on BC, 2) assess the drug’s ability to cause necrosis, 3) assess immune response within the tumor, microenvironment and systemically prior to surgical resection, and 4) understand the genetic pathways involved in immune activity. Methods: Women awaiting surgery for newly diagnosed early-stage intermediate or high-grade T1-T2 invasive BC were recruited to the trial. The study has two parts. Part I was a randomized (2:1) open label trial comparing 1-3 doses of INT230-6 injected weekly versus no treatment prior to surgery to evaluate safety, feasibility, and optimal drug dosing. Part II was a double-blinded randomized (2:1) trial where patients received one IT dose of INT230-6 vs saline injection IT. Results: We successfully recruited 91 patients with age ranges of 40-77 yrs (mean of 60 yrs) with tumor size ranging from 1.1 - 4.8 cm (mean 2.5 cm; SD 0.9 cm). The most common (>10%) AEs were injection site pain, injection site reaction and nausea/vomiting. Approximately 90% of AEs were grade 1. In the study INT230-6 induced necrosis in 64% of subjects (37 out of 58, range 0 to 100%); whereas saline induced partial necrosis in 25% of patients (5 out of 20, range 0 to 10%). The table below shows the results of necrosis for INT230-6 use in the entire study compared to saline injection for all subjects and those with tumors of size T2. A single injection of INT230-6 caused necrosis in various histologies, including invasive lobular carcinoma. Gene expression analysis showed significant differential gene expression between the baseline biopsy and surgical specimens using INT230-6. Pathway analysis identified genes associated with TCR signaling, B cells and T cell activation that were significantly upregulated in the post INT230-6 treatment samples. There was a relative increase in CD4 and CD8 T cells and B and mast cells. Conclusion: Preliminary evidence shows that a single dose of INT230-6 can cause significant intratumoral necrosis compared to saline especially in tumors >2. cm. INT230-6 stimulates an immune response in breast cancers prior to surgery with minimal adverse effects and good tolerability. Given its immune activation properties, INT230-6 shows promising potential in future breast cancer neoadjuvant studies. Table 1: INVINCIBLE Study Tumor Necrosis Results Intratumoral INT230-6 injection compared to IT saline injection Citation Format: Angel Arnaout, Lewis Bender, Megan Hopkins, Vanessa Lopez Ozuna, Linda Liao, Susan Robertson, Vida Talebian, Kianoosh Keyhanian, Arif Awan, Franco Abbate, Ian Walters, Gregory Pond, John Bartlett, Lazlo Radvanyi, Melanie Spears. Intratumoral dosing of INT230-6 in Early-Stage Breast Cancer Patients Induces Tumor Cell Necrosis and Immunomodulatory Effects: A Phase II Randomized Window-Of-Opportunity Study – the INVINCIBLE Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-03.
Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector‐based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well‐described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
Purpose: Cancer is now the leading cause of non-AIDS death in the US population with HIV. People living with HIV (PLWH) are known to have lower cancer treatment rates and worse cancer outcomes. Disparate cancer treatment is driven by health system, patient, and clinician factors. Little attention has been given to the factors oncologists consider when making cancer treatment recommendations to PLWH. This study sought to examine oncologists' knowledge, attitudes, and practices that influence cancer treatment decision-making.Methods and Materials: This study used qualitative methods to explore oncologists' treatment decision-making processes for PLWH and cancer. The sample included 25 radiation, medical, and surgical oncologists from 2 academic centers and 5 community practices. The interview domains were developed from the Andersen Healthcare Utilization Model, the Health Belief Model, and the PEN-3 Model, as well as our prior survey research.Results: This study describes elements of cancer treatment decision-making for PLWH. Oncologists highlighted the need for formal HIV education to support cancer treatment. One main concern with patient-provider interactions pertained to maintaining patient confidentiality during clinical encounters. Lastly, the importance of multidisciplinary care among health care providers allowed oncologists to facilitate both cancer care and logistical support.Conclusions: As cancer becomes an increasingly common cause of death among PLWH, it is critical to understand the drivers of the observed disparities in cancer treatment. To our knowledge, this is the first qualitative study to describe oncologists'
The clinical significance of the tumor‐immune interaction in breast cancer is now established, and tumor‐infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple‐negative (estrogen receptor, progesterone receptor, and HER2‐negative) breast cancer and HER2‐positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state‐of‐the‐art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false‐positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in‐depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple‐negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Purpose The development of oestrogen resistance is a major challenge in managing hormone-sensitive metastatic breast cancer. Saracatinib (AZD0530), an oral Src kinase inhibitor, prevents oestrogen resistance in animal models and reduces osteoclast activity. We aimed to evaluate the efficacy of saracatinib addition to aromatase inhibitors (AI) in patients with hormone receptor-positive metastatic breast cancer. Methods This phase II multicentre double-blinded randomised trial allocated post-menopausal women to AI with either saracatinib or placebo (1:1 ratio). Patients were stratified into an “AI-sensitive/naïve” group who received anastrozole and “prior-AI” group who received exemestane. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and toxicity. Results 140 patients were randomised from 20 UK centres to saracatinib/AI ( n = 69) or placebo/AI ( n = 71). Saracatinib was not associated with an improved PFS (3.7 months v. 5.6 months placebo/AI) and did not reduce likelihood of bony progression. There was no benefit in OS or ORR. Effects were consistent in “AI-sensitive/naive” and “prior-AI” sub-groups. Saracatinib was well tolerated with dose reductions in 16% and the main side effects were gastrointestinal, hypophosphatemia and rash. Conclusion Saracatinib did not improve outcomes in post-menopausal women with metastatic breast cancer. There was no observed beneficial effect on bone metastases. CRUKE/11/023, ISRCTN23804370.
Early triple-negative breast cancer (eTNBC) is molecularly heterogenous, with differential prognosis. We aimed to identify new biological subgroups (B-grp) of eTNBC via an integrative clustering pipeline (ICP) and evaluate the clinical value of these B-grp in a large randomised clinical trial. TACT2 was a phase 3, randomised trial testing adjuvant accelerated versus standard Epirubicin in early breast cancer. From TACT2, 551 eTNBC tumours were stratified into training (n=367) and testing (n=184) by treatment arm. Expressions of 758 genes (GE) and Triple-Negative Subtypes ( TNS; Burstein CCR 2015 ) of tumour were profiled by nCounter@ Breast Cancer 360TM. Immunohistochemistry expressions (IHC) of HER2, EGFR and CK5/6 were assessed. Clinicopathological features (ClinPath) included age, nodal status, tumour size and grade. The ICP included random forest (RF) and 9 unique clustering methods with hypergeometric test to reconcile clustering results to a final output. Survival endpoint was time to recurrence (TTR) for multivariable cox regression (mCox), of which the goodness-of-fit was assessed by chi-square, brier score and integrated calibration index. The ICP returned 4 B-grp using GE, IHC and ClinPath of the training set. GE was the main factor of clustering, summarising B-grp into immune-enriched (IM), Luminal-AR (LAR), mesenchymal like (MES) and basal like (BL). IM and LAR contained mainly TNS-BLIA and TNS-LAR, respectively. Both MES and BL comprised TNS-BLIA, TNS-BLIS and TNS-MES. The RF was trained using GE as unimodal single-sample predictor to assign the B-grp on the testing set. Adding B-grp to ClinPath yielded more accurate 5-year TTR prediction for test samples when compared to TNS (Table).Table: 307PComparing the goodness-of-fit of three mCox models using chi-square, brier score and integrated calibration indexClinPathClinPath + TNSClinPath + B-grpChi-square19.2759.9832.29Chi-square (against the ClinPath model)-40.71 (p < 0.0001)16.02 (p = 0.001)Brier score0.14770.15440.1425Integrated calibration index0.0210.0640.019Brier score is the mean square difference between the true classes (0 = no recurrence, 1 = recurrence) and the predicted probabilities at given time point. Integrated calibration index is the weighted absolute difference between the calibration curve and the diagonal line of best fit. Open table in a new tab . Brier score is the mean square difference between the true classes (0 = no recurrence, 1 = recurrence) and the predicted probabilities at given time point. Integrated calibration index is the weighted absolute difference between the calibration curve and the diagonal line of best fit. We identified 4 eTNBC B-grp based on distinct biology which provided more accurate 5-year TTR prediction in addition to ClinPath than TNS. The association of the B-grp with survival for other treatments could be further evaluated.
Background: The extent of the burden of erectile dysfunction and its associated factors remains unclear. The aim of this study was to investigate the factors associated with ED and its prevalence among MLHIV in northern Tanzania. Methods: A hospital-based, multi-center, cross-sectional study was conducted on MLHIV aged 18 years and above in northern Tanzania. Outcome: The risk factors for ED and the prevalence of such risk factors among MLHIV was assessed and evaluated through a multivariate logistic regression analysis adjusted for depression symptoms using the Patient Health Questionnaire-9 (PHQ9) scale; anxiety disorders using the Generalized Anxiety Disorder Assessment (GAD-7); ART adherence; viral load; initial regimen date; ART regimen; and sexual risk behaviors. Results: Data for 366 participants with amedian age of 50 years (IQR 38-57 years) were available for analysis. Approximately three in four (74.6%) MLHIV had ED (of any severity), whereas 37.7% had mild ED. The majority (96.5%) of the participants had low testosterone, two in three (66.7%) had depressive symptoms, and close to half of the participants (48.4%) had anxiety. Age, lack of engagement in vigorous physical activity, depression, and self-reported good adherence to antiretroviral therapy (ART) were associated with ED in a multivariate logistic regression analysis (p=0.004, p =0.006, p=0.07, p=0.006, and p=0.004, respectively). Conclusion: There is a high prevalence of ED among MLHIV in northern Tanzania. Erectile dysfunction should be regarded as one of the comorbidities associated with HIV and should be routinely screened for among MLHIV in CTC clinics.
533 Background: Gene-expression profiling tests (e.g. Oncotype, Mammaprint, Prosignia, Breast Cancer Index and EndoPredict) are widely used in the care of patients with early-stage hormone positive breast cancer (node negative or 1-3 lymph nodes). However, these tests are resource intensive, and few studies have compared their value with either free and widely available clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS-5) or tools that combine genomic testing with clinico-pathologic data (e.g. RSClin). The TEAM pathology substudy population was used to compare these different predicted model scores with outcomes. Methods: The TEAM pathology study consists of 3284 postmenopausal hormone positive breast cancer patients treated with either exemestane or tamoxifen followed by exemestane. Accrual was from 2001 to 2006. Genes comprising the multi-parametric Oncotype Dx were used to train signatures to create true assay results. Patient data was then used to calculate recurrence scores through various tools. This included clinico-pathologic models and their respective endpoints PREDICT 2.1 (overall survival at 5 years), INFLUENCE 2.0 (distant metastasis at 5 years), CTS-5 (distant recurrence risk at year 5-10), the purely genomic Oncotype Dx trained results (distant recurrence risk at 9 years), as well as the new clinico-pathologic RSClin (distant recurrence risk at 10 years). We compared the level of association between these predictive model scores using Spearman correlation coefficients. The prognostic ability of each model was contrasted for each outcome using Harrell’s C-statistic. Results: Results were available for CTS-5 (3022 patients), INFLUENCE 2.0 (3485 patients), ODx-trained (3825 patients), and RSClin (3029 patients). Correlation coefficients showed low correlation between Influence ( r= 0.25) and CTS-5 ( r= 0.17) with Oncotype-Dx trained results, and high correlation between RSClin ( r = 0.84) and Oncotype-Dx trained results. The concordance index was similar (0.65 to 0.68) for all models with distant metastasis-free survival as the outcome. Analysis is ongoing and further results will be available at the time of presentation. Conclusions: Other clinico-pathologic tools such as Influence 2.0 and CTS-5 have good prognostic ability when compared to Oncotype Dx-trained results and RSClin. [Table: see text]
Background HIV and antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors, may increase the risk of Metabolic Syndrome (MetS) among people living with HIV (PLHIV). However, following the introduction of better drugs like dolutegravir, data on the burden of MetS are limited. This study aimed to assess the prevalence of MetS and associated factors among PLHIV on antiretroviral therapy (ART) in Tanzania. Methods This was a cross-sectional study among PLHIV aged ≥ 18 years on antiretroviral therapy for ≥ 1 year at Bugando Medical Centre in Mwanza conducted in 2020. Demographic and healthy-lifestyle-related non-communicable disease risk factors data were collected. Additionally, data on lipid profile, blood glucose, blood pressure, and waist circumference were collected for analysis of MetS according to the International Diabetes Federation criteria. Factors associated with MetS were assessed using logistic regression. A P ≤ 0.05 was considered statistically significant. Results Data for 223 participants were analyzed. The mean (SD) age was 44 (± 12) years and 79.8% (178) were females. A majority 78% (174) were on a tenofovir, lamivudine,and dolutegravir regimen. About 12.1% (27) were either current or past smokers, 45.3% (101) were past alcohol drinkers, 22.9% (51) were current drinkers, 12.1% (27) reported taking ≥ 5 servings of vegetables and fruits per day and 5.8% (13) were physically inactive. The prevalence of MetS was 22.9%. The only factors that were associated with Mets were fat mass index and adequate intake of vegetables and fruits, (adjusted odds ratio (aOR) 2.9, 95% CI 1.0, 7.9, P = 0.04) and (aOR1.2, 95% CI 1.0, 1.3, P = 0.02), respectively). Conclusion The prevalence of MetS remains high among PLHIV. Adiposity and adequate fruit and vegetable intake increased the risk. The introduction of new ART regimens shows no effect on MetS prevalence. Research is needed to understand how lifestyle changes could reduce MetS in PLHIV.