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INTRODUCTION: While increasing evidence shows that hospice and palliative care interventions in the ED can benefit patients and systems, little exists on the feasibility and effectiveness of identifying patients in the ED who might benefit from hospice care. Our aim was to evaluate the effect of a clinical care pathway on the identification of patients who would benefit from hospice in an academic medical center ED setting. METHODS: We instituted a clinical pathway for ED patients with potential need for or already enrolled in hospice. This pathway was digitally embedded in the electronic health record and made available to ED physicians, APPs and staff in a non-interruptive fashion. Patient and visit characteristics were evaluated for the six months before (05/04/2021-10/4/2021) and after (10/5/2021-05/04/2022) implementation. RESULTS: After pathway implementation, more patients were identified as appropriate for hospice and ED length of stay (LOS) for qualifying patients decreased by a median of 2.9 h. Social work consultation for hospice evaluation increased, and more patients were discharged from the ED with hospice. As more patients were identified with end-of-life care needs, the number of patients admitted to the hospital increased. However, more patients were admitted under observation status, and admission LOS decreased by a median of 18.4 h. CONCLUSION: This non-interruptive, digitally embedded clinical care pathway provided guidance for ED physicians and APPs to initiate hospice referrals. More patients received social work consultation and were identified as hospice eligible. Those patients admitted to the hospital had a decrease in both ED and hospital admission LOS.
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Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Humanos , Tempo de Internação , Procedimentos Clínicos , Serviço Hospitalar de Emergência , Estudos RetrospectivosRESUMO
BACKGROUND: Emergency department visits associated with Coronavirus Disease 2019 (COVID-19) continue to indicate racial and ethnic inequities. We describe the sociodemographic characteristics of individuals receiving COVID-19 vaccination in the emergency department and compare with an outpatient clinic population and emergency department (ED) patients who were eligible but not vaccinated. METHODS: We conducted a retrospective analysis of electronic health record data at an urban academic ED from May to July 2021. The primary aim was to characterize the ED-vaccinated population, compared with ED patients who were eligible but unvaccinated and the physically adjacent outpatient vaccination clinic population. RESULTS: A total of 627 COVID-19 vaccinations were administered in the ED. Overall, 49% of ED patients during that time had already received at least one vaccine dose prior to ED arrival. Hispanic, non-Hispanic Black patients, and patients on non-commercial insurance had higher odds of being vaccinated in the ED as compared with outpatient clinic setting. Among eligible ED patients, men and patients who were uninsured/self-pay were more likely to accept ED vaccination. CONCLUSIONS: This ED COVID-19 vaccination campaign demonstrated a higher likelihood to vaccinate individuals from racial/ethnic minority groups, those with high social vulnerability, and non-commercial insurance, when compared with a co-located outpatient vaccination clinic.
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COVID-19 , Grupos Minoritários , Masculino , Humanos , Etnicidade , Minorias Étnicas e Raciais , Vacinas contra COVID-19/uso terapêutico , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Serviço Hospitalar de Emergência , Programas de ImunizaçãoRESUMO
HIV-1 superinfection (SI) occurs when an infected individual acquires a distinct new viral strain. The rate of superinfection may be reflective of the underlying HIV risk in a population. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 clinical trial demonstrated that women who used a tenofovir-containing microbicide gel had lower rates of HIV infection than women using a placebo gel. Women who contracted HIV-1 during the trial were screened for the occurrence of superinfection by next-generation sequencing of the viral gag and env genes. There were two cases (one in each trial arm) of subtype C superinfection identified from the 76 women with primary infection screened at two time points (rate of superinfection, 1.5/100 person-years). Both women experienced a >0.5-log increase in viral load during the window when superinfection occurred. The rate of superinfection was significantly lower than the overall primary HIV incidence in the microbicide trial (incidence rate ratio [IRR], 0.20; P=0.003). The women who seroconverted during the trial reported a significant increase in sexual contact with their stable partner 4 months after seroconversion (P<0.001), which may have lowered the risk of superinfection in this population. The lower frequency of SI compared to the primary incidence is in contrast to a report from a general heterosexual African population but agrees with a study of high-risk women in Kenya. A better understanding of the rate of HIV superinfection could have important implications for ongoing HIV vaccine research.
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Anti-Infecciosos/uso terapêutico , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , HIV-1/isolamento & purificação , Superinfecção/diagnóstico , Cremes, Espumas e Géis Vaginais/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Quimioprevenção/métodos , Feminino , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/genética , Humanos , Incidência , Quênia , Organofosfonatos/uso terapêutico , Análise de Sequência de DNA , África do Sul , Superinfecção/epidemiologia , Tenofovir , Carga Viral , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genéticaRESUMO
HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/µL and <250 cells/µL). The study enrolled 117 antiretroviral naïve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count = 233 cells/µL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results.
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Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/genética , Progressão da Doença , HIV-1/genética , Tolerância Imunológica/genética , Complexo AIDS Demência/epidemiologia , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Inquéritos e Questionários , Uganda/epidemiologia , Adulto JovemRESUMO
Objectives: To evaluate whether subcutaneous neutralizing monoclonal antibody (mAb) treatment given in the emergency department (ED) setting was associated with reduced hospitalizations, mortality, and severity of disease when compared to nontreatment among mAb-eligible patients with coronavirus disease 2019 (COVID-19). Methods: This retrospective observational cohort study of ED patients utilized a propensity score-matched analysis to compare patients who received subcutaneous casirivimab and imdevimab mAb to nontreated COVID-19 control patients in November-December 2021. The primary outcome was all-cause hospitalization within 28 days, and secondary outcomes were 90-day hospitalization, 28- and 90-day mortality, and ED length of stay (LOS). Results: Of 1340 patients included in the analysis, 490 received subcutaneous casirivimab and imdevimab, and 850 did not received them. There was no difference observed for 28-day hospitalization (8.4% vs. 10.6%; adjusted odds ratio [aOR] 0.79, 95% confidence intervals [CI] 0.53-1.17) or 90-day hospitalization (11.6% vs. 12.5%; aOR 0.93, 95% CI 0.65-1.31). However, mortality at both the 28-day and 90-day timepoints was substantially lower in the treated group (28-day 0.6% vs. 3.1%; aOR 0.18, 95% CI 0.08-0.41; 90-day 0.6% vs. 3.9%; aOR 0.14, 95% CI 0.06-0.36). Among hospitalized patients, treated patients had shorter hospital LOS (5.7 vs. 11.4 days; adjusted rate ratio [aRR] 0.47, 95% CI 0.33-0.69), shorter intensive care unit LOS (3.8 vs. 10.2 days; aRR 0.22, 95% CI 0.14-0.35), and the severity of hospitalization was lower (aOR 0.45, 95% CI 0.21-0.97) compared to untreated. Conclusions: Among ED patients who presented for symptomatic COVID-19 during the Delta variant phase, ED subcutaneous casirivimab/imdevimab treatment was not associated with a decrease in hospitalizations. However, treatment was associated with lower mortality at 28 and 90 days, hospital LOS, and overall severity of illness.
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BACKGROUND AND OBJECTIVES: Clinical pathways have been found effective for improving adherence to evidence-based guidelines, thus providing better patient outcomes. As coronavirus disease-2019 (COVID-19) clinical guidance changed rapidly and evolved, a large hospital system in Colorado established clinical pathways within the electronic health record to guide clinical practice and provide the most up-to-date information to frontline providers. METHODS: On March 12, 2020, a system-wide multidisciplinary committee of specialists in emergency medicine, hospital medicine, surgery, intensive care, infectious disease, pharmacy, care management, virtual health, informatics, and primary care was recruited to develop clinical guidelines for COVID-19 patient care based on the limited available evidence and consensus. These guidelines were organized into novel noninterruptive digitally embedded pathways in the electronic health record (Epic Systems, Verona, Wisconsin) and made available to nurses and providers at all sites of care. Pathway utilization data were analyzed from March 14 to December 31, 2020. Retrospective pathway utilization was stratified by each care setting and compared with Colorado hospitalization rates. This project was designated as a quality improvement initiative. RESULTS: Nine unique pathways were developed, including emergency medicine, ambulatory, inpatient, and surgical care guidelines. Pathway data were analyzed from March 14 to December 31, 2020, and showed that COVID-19 clinical pathways were used 21 099 times. Eighty-one percent of pathway utilization occurred in the emergency department setting, and 92.4% applied embedded testing recommendations. A total of 3474 distinct providers employed these pathways for patient care. CONCLUSIONS: Noninterruptive digitally embedded clinical care pathways were broadly utilized during the early part of the COVID-19 pandemic in Colorado and influenced care across many care settings. This clinical guidance was most highly utilized in the emergency department setting. This shows an opportunity to leverage noninterruptive technology at the point of care to guide clinical decision-making and practice.
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COVID-19 , Humanos , COVID-19/epidemiologia , Procedimentos Clínicos , Fluxo de Trabalho , Pandemias , Estudos RetrospectivosRESUMO
BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has presented the healthcare system with a plethora of challenges, including implementation of an efficient vaccination strategy. Mass vaccinations have been used during previous pandemics; however, the associated data have largely been limited to theoretical simulations and post hoc analysis. METHODS: An innovative data collection tool was created to deliver real-time data analysis during a drive-through mass vaccination. Patients were assigned unique identification numbers at the clinic entrance. Using these identification numbers, and the web-based spreadsheet, patients were tracked throughout the vaccination process. Static timestamps corresponding to the entry and exit at each checkpoint were recorded in real time. RESULTS: Data were collected on a total of 3,744 vehicles over five clinic days. Total time was collected, from entry to exit, on 2,860 vehicles. Registration and vaccination times were collected on 3,111 vehicles. Of the vehicles sampled, 1,588 (42%) had data points associated with all checkpoints. CONCLUSIONS: This open-source, innovative data collection tool was successfully implemented in our mass vaccination clinic for tracking patients in real time providing actionable data on overall throughput efficiency. This cost-effective tool can be used on a variety of healthcare-related projects to provide data-driven evaluation on the efficiency of care.
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Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Coleta de Dados , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , VacinaçãoRESUMO
OBJECTIVE: There are significantly fewer women than men in leadership roles in health care. Previous studies have shown that, overall, male physicians earn nearly $20,000 more annually than their female physician colleagues after adjusting for confounding factors. However, there has not been a description of physician leadership compensation in relation to gender. METHODS: This was a successive cross-sectional observation study design of 154 emergency departments in the United States from 5 years (2013, 2015-2018) using Association of Academic Chairs in Emergency Medicine and Academy of Administrators in Academic EM survey data. The primary variable of interest, leadership role, was attained by recoding the survey responses to assign primary job duty into four main categories: no leadership role, operations leadership, education leadership, and executive leadership. RESULTS: Overall, 8820 responses were included. Across all survey years, the mean (±SD) percentage of women in any leadership role was significantly less than men (44.5% [95% CI: 42.8, 46.2%] vs. 55.3% [95% CI: 54.1, 56.5%]). Women in leadership roles worked more clinical hours than men in the same position (female median = 1008, male median = 960). Women also had significantly lower salaries than men at each of the 5-year time points that data are reported, with unadjusted mean salary differences of -$54,409 per year for executives, -$27,803 for operational leaders, and -$17,803 for education leaders. CONCLUSIONS: Female physicians hold fewer leadership roles in academic emergency medicine (EM), and when they do, they work more clinical hours and are paid less than male physicians. As a specialty, EM should continue to investigate and report on gender achievement disparities as work is done to rectify the system inequalities.
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Medicina de Emergência , Médicas , Estudos Transversais , Medicina de Emergência/educação , Docentes de Medicina , Feminino , Humanos , Liderança , Masculino , Salários e Benefícios , Estados UnidosRESUMO
Drive-through clinics have previously been utilized in vaccination efforts and are now being more widely adopted for COVID-19 vaccination in different parts of the world by offering many advantages including utilizing existing infrastructure, large daily throughput and enforcing social distancing by default. Successful, effective, and efficient drive-through facilities require a suitable site and keen focus on layout and process design. To demonstrate the role that high fidelity computer simulation can play in planning and design of drive-through mass vaccination clinics, we used multiple integrated discrete event simulation (DES) and agent-based modelling methods. This method using AnyLogic simulation software to aid in planning, design, and implementation of one of the largest and most successful early COVID-19 mass vaccination clinics operated by UCHealth in Denver, Colorado. Simulations proved to be helpful in aiding the optimization of UCHealth drive through mass vaccination clinic design and operations by exposing potential bottlenecks, overflows, and queueing, and clarifying the necessary number of supporting staff. Simulation results informed the target number of vaccinations and necessary processing times for different drive through station set ups and clinic formats. We found that modern simulation tools with advanced visual and analytical capabilities to be very useful for effective planning, design, and operations management of mass vaccination facilities.
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An estimated 4.7 billion people live in regions exposed to soil-transmitted helminths, intestinal parasites that have significant impacts on the health of women smallholder farmers. The goal of this trial was to determine whether treatment with albendazole impacts the work capacity of these farmers. This is a prospective double-blind, randomized effectiveness trial. Participants (N = 250) were randomly selected from safe motherhood groups in the Democratic Republic of Congo. Prevalence/intensity of hookworm infection, hemoglobin, and demographics was obtained. At study (Time = 0), participants were randomized into treatment (albendazole 400 mg) and placebo (similar placebo tablet) groups. A step test was administered as a proxy metric for work capacity. Work capacity was defined as ∆heart rate before and after 3 minutes of step testing, in beats per minute. At study (time = 7 months), the step test was repeated and work capacity remeasured. The ∆work capacity (time = 0 minus time = 7 months) was the primary outcome. Investigators/field assistants were blinded to who was enrolled in groups, hookworm status, and step test results. Regression showed highly significant interactive effects of hookworm status and treatment group relative to ∆work capacity after controlling for resting pulse rate and age (P < 0.002). Estimated marginal means for work capacity (WC) for each of four groups (hookworm positive plus placebo, hookworm positive plus treatment, hookworm negative plus placebo, and hookworm negative plus treatment) showed women who were hookworm positive and received treatment decreased heart rate by 9.744 (95% confidence interval [CI]: 6.42, 13.07) beats per minute (increased WC), whereas women who were hookworm positive and received placebo saw a nonsignificant decrease of 0.034 (95% CI: -3.16, 3.84) beats per minute. Treatment with albendazole was associated with improved aerobic work capacity posttreatment. Given modest costs of drug distributions, risk benefits of periodic deworming warrants further study in larger controlled trials.
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Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Fazendeiros , Frequência Cardíaca/fisiologia , Infecções por Uncinaria/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , HumanosRESUMO
We analyzed the impact of HIV viral load on the performance of a limiting antigen avidity enzyme immunoassay (LAg-Avidity assay) and determined if this assay could be used to identify viral breakthrough. Three groups of samples were tested: (1) 18 individuals (30 samples) previously identified as elite suppressors; (2) 18 individuals (72 samples) who were continually suppressed on antiretroviral treatment (ART) with 1 sample before and 2-6 samples (one/year) after ART initiation; and (3) 20 individuals (179 samples) on ART who had evidence of viral breakthrough (>400 copies/ml) with subsequent viral suppression. Elite suppressors had the lowest LAg-Avidity assay values. Among those who were continually suppressed on ART, 83% (15/18) had LAg-Avidity assay values that decreased over time. Although the LAg-Avidity assay on a single sample cannot identify when a viral breakthrough occurs, paired longitudinal samples could identify viral breakthrough (sensitivity: 65%, specificity: 84%).
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Ensaio de Imunoadsorção Enzimática/métodos , Antígenos HIV/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Superinfecção/diagnóstico , Carga Viral , Humanos , Sensibilidade e Especificidade , Resposta Viral SustentadaRESUMO
This paper describes design of a low cost, ultrasound gel from local products applying aspects of Human Centered Design methodology. A multidisciplinary team worked with clinicians who use ultrasound where commercial gel is cost prohibitive and scarce. The team followed the format outlined in the Ideo Took Kit. Research began by defining the challenge "how to create locally available alternative ultrasound gel for a low-resourced environment? The "End-Users," were identified as clinicians who use ultrasound in Democratic Republic of the Congo and Ethiopia. An expert group was identified and queried for possible alternatives to commercial gel. Responses included shampoo, oils, water and cornstarch. Cornstarch, while a reasonable solution, was either not available or too expensive. We then sought deeper knowledge of locally sources materials from local experts, market vendors, to develop a similar product. Suggested solutions gleaned from these interviews were collected and used to create ultrasound gel accounting for cost, image quality, manufacturing capability. Initial prototypes used cassava root flour from Great Lakes Region (DRC, Rwanda, Uganda, Tanzania) and West Africa, and bula from Ethiopia. Prototypes were tested in the field and resulting images evaluated by our user group. A final prototype was then selected. Cassava and bula at a 32 part water, 8 part flour and 4 part salt, heated, mixed then cooled was the product design of choice.
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Géis , Avaliação de Programas e Projetos de Saúde , Ultrassom , África , Custos e Análise de Custo , Desenho de Equipamento , Géis/economia , Humanos , Manihot , Ultrassom/economiaRESUMO
Assays used for HIV cross-sectional incidence testing can misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed the frequency and factors associated with false-recent misclassification on subjects from Quangxi, China known to have long-term infection using the limited antigen-avidity assay (LAg-Avidity). Stored samples from treatment-naive individuals from Guangxi, China were tested using the LAg-Avidity. A total of 362 samples from individuals known to be infected 2 to 13.5 years were tested and the false-recent rate (FRR), the frequency of samples with a positive result, was determined at different cutoff values of the assay. Additionally, factors associated with misclassification were determined. The FRR of the LAg-Avidity was 1.1% (4/362) using a cutoff of 1.5 normalized optical density units (OD-n). All four samples had viral loads >1,000 copies/ml. Using a cutoff of 3.0 OD-n the FRR was 5.5% (20/362), with four samples having viral loads <1,000 copies/ml. Factors associated with a higher odds of misclassification were female gender (OR 7.7, 95% CI 1.0-56.4) and being a female sex worker (OR 31.3, 95% CI 4.0-242). At the higher cutoff, being of Zhuang decent, relative to Han, had higher odds of misclassification (OR 6.2, 95% CI 1.99-19.0). The LAg-Avidity assay had a low FRR in this Chinese population. Further investigations of the higher frequency of low LAg-Avidity results seen in female sex workers and individuals of Zhuang descent should be explored in a larger study.
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Afinidade de Anticorpos , Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Sobreviventes , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
OBJECTIVE: This study examined HIV superinfection in HIV-infected women postpartum, and its association with mother-to-child transmission (MTCT). DESIGN: Plasma samples were obtained from HIV-infected women who transmitted HIV to their infants after 6 weeks of age (transmitters, nâ=â91) and HIV-infected women who did not transmit HIV to their infants (nontransmitters, nâ=â91). These women were originally enrolled in a randomized trial for prevention of MTCT of HIV in Malawi (Post-Exposure Prophylaxis of Infants trial in Malawi). METHODS: Two HIV genomic regions (p24 and gp41) were analyzed by next-generation sequencing for HIV superinfection. HIV superinfection was established if the follow-up sample contained a new, phylogenetically distinct viral population. HIV superinfection and transmission risk were examined by multiple logistic regression, adjusted for Post-Exposure Prophylaxis of Infants study arm, baseline viral load, baseline CD4 cell count, time to resumption of sex, and breastfeeding duration. RESULTS: Transmitters had lower baseline CD4 cell counts (Pâ=â0.001) and higher viral loads (Pâ<â0.0001) compared with nontransmitters. There were five cases of superinfection among transmitters (rate of superinfectionâ=â4.7/100 person-years) compared with five cases among the nontransmitters (rate of superinfectionâ=â4.4/100 person-years; Pâ=â0.78). HIV superinfection was not associated with increased risk of postnatal MTCT of HIV after controlling for maternal age, baseline viral load, and CD4 cell count (adjusted odds ratioâ=â2.32, Pâ=â0.30). Longer breastfeeding duration was independently associated with a lower risk of HIV superinfection after controlling for study arm and baseline viral load (Pâ=â0.05). CONCLUSION: There was a significant level of HIV superinfection in women postpartum, but this was not associated with an increased risk of MTCT via breastfeeding.
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Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas , Período Pós-Parto , Superinfecção/epidemiologia , Superinfecção/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Contagem de Linfócito CD4 , Pré-Escolar , Feminino , Genótipo , Técnicas de Genotipagem , Proteína do Núcleo p24 do HIV/genética , Proteína gp41 do Envelope de HIV/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Malaui/epidemiologia , Profilaxia Pós-Exposição , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sequência de DNA , Comportamento Sexual , Carga Viral , Adulto JovemRESUMO
HIV elite suppressors (ES) or controllers are individuals achieving control of viremia by their natural immunological mechanisms without highly active antiretroviral therapy (HAART). Study of the mechanisms responsible for the immunological suppression of viremia in ES may lead to the detection of individuals with ES and the effective control of HIV infection. We hypothesize that plasma glycoproteins play essential roles in the immune system of ES since plasma proteins are critical and highly relevant in anti-viral immunity and most plasma proteins are glycoproteins. To examine glycoproteins associated with ES, plasma samples from ES individuals (n=20), and from individuals on HAART (n=20), with AIDS (n=20), and no HIV infection (n=10) were analyzed by quantitative glycoproteomics. We found that a number of glycoproteins changed between ES versus HAART, AIDS and HIV- individuals. In sharp contrast, the level of plasma glycoproteins in the HAART cohort showed fewer changes compared with AIDS and HIV- individuals. These results showed that although both ES and HAART effectively suppress viremia, ES appeared to profoundly affect immunologically relevant glycoproteins in plasma as consequence of or support for anti-viral immunity. Bioinformatic analysis revealed that altered proteins in ES plasma were mainly associated with inflammation. This analysis suggests that overlapping, while distinguishable, glycoprotein profiles for inflammation and immune activation appeared to be present between ES and non-ES (HAART+AIDS) cohorts, indicating different triggers for inflammation and immune activation between natural and treatment-related viral suppression.
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Proteínas Sanguíneas/química , Glicômica , Glicoproteínas/química , Infecções por HIV/sangue , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Proteínas Sanguíneas/imunologia , Estudos de Coortes , Feminino , Glicoproteínas/sangue , Glicoproteínas/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Masculino , Espectrometria de MassasRESUMO
OBJECTIVE: To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers (FSWs) in Kampala, Uganda. DESIGN: A retrospective analysis of individuals who participated in a clinical cohort study among high-risk FSWs in Kampala, Uganda. METHODS: Plasma samples from HIV-infected FSWs in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41 HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSWs from the same cohort, and incidence rate ratios were compared. RESULTS: The rate of superinfection in these women (7/85; 3.4/100 person-years) was not significantly different from the rate of primary infection in the same population (3.7/100 person-years; incidence rate ratio = 0.91, P = 0.42). Seven women also entered the study dual-infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (P = 0.05), and trended to be older and more likely to be widowed (P = 0.07). CONCLUSIONS: In this cohort of FSWs, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.
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Infecções por HIV , HIV-1 , Profissionais do Sexo/estatística & dados numéricos , Parceiros Sexuais , Superinfecção , Adulto , Fatores Etários , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , HIV-1/genética , Humanos , Incidência , Estudos Retrospectivos , Superinfecção/epidemiologia , Superinfecção/imunologia , Uganda/epidemiologia , Carga ViralRESUMO
BACKGROUND: Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays. METHODS: All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA) which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1) 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2) 72 samples from 18 adults on antiretroviral therapy (ART), with 1 sample before and 2-6 samples after ART initiation, and (3) 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA) and with subsequent viral suppression. RESULTS: For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n) and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63)/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1) values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2) values that increased after viral breakthrough, and (3) values that did not change with viral breakthrough. CONCLUSIONS: Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Afinidade de Anticorpos/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Fármacos Anti-HIV/farmacologia , Afinidade de Anticorpos/efeitos dos fármacos , Infecções por HIV/classificação , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Fatores de TempoRESUMO
A high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ≥9.3 kPa (cases=133) and normal controls (n=133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR=1.19, p=0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR=1.54, p<0.001); however, the opposite was observed in HIV-negative individuals (adjMOR=0.57, p=0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease.