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1.
IEEE Trans Vis Comput Graph ; 29(11): 4525-4534, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37788199

RESUMO

Real-time communication with immersive 360° video can enable users to be telepresent within a remotely streamed environment. Increasingly, users are shifting to mobile devices and connecting to the Internet via mobile-cellular networks. As the ideal media for 360° videos, some VR headsets now also come with cellular capacity, giving them potential for mobile applications. However, streaming high-quality 360° live video poses challenges for network bandwidth, particularly on cellular connections. To reduce bandwidth requirements, videos can be compressed using viewport-adaptive streaming or foveated rendering techniques. Such approaches require very low latency in order to be effective, which has previously limited their applications on traditional cellular networks. In this work, we demonstrate an end-to-end virtual reality telepresence system that streams ∼6K 360° video over 5G millimeter-wave (mmW) radio. Our use of 5G technologies, in conjunction with mobile edge compute nodes, substantially reduces latency when compared with existing 4G networks, enabling high-efficiency foveated compression over modern cellular networks on par with WiFi. We performed a technical evaluation of our system's visual quality post-compression with peak signal-to-noise ratio (PSNR) and FOVVideoVDP. We also conducted a user study to evaluate users' sensitivity to compressed video. Our findings demonstrate that our system achieves visually indistinguishable video streams while using up to 80% less data when compared with un-foveated video. We demonstrate our video compression system in the context of an immersive, telepresent video calling application.

2.
Tumour Virus Res ; 13: 200237, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35460939

RESUMO

BACKGROUND: HIV has been shown to increase the likelihood of oral HPV infection. In this study, we evaluated the risk of oral HPV in HIV infected patients compared with HIV-negative controls. METHODS: 101 healthy adult volunteers (HIV-) and 245 adults living with HIV infection (HIV+) were recruited from 5 academic medical centers. Questionnaires and saliva samples were obtained every 3-8 months over a period of 2 years (2015-2017). DNA was isolated from the saliva samples and tested for 18 high- and low-risk genotypes. RESULTS: Oral HPV was detected in 23% of HIV + vs. 10% of HIV- participants (p < 0.0001). Men had a higher oral HPV prevalence than women (27% vs. 15% HIV+, p = 0.03, 16% vs. 5% HIV-, p = 0.01). Risk factors among HIV + participants included more lifetime deep kissing and oral sex partners, and history of AIDS. Persistent oral HPV was detected in 23% of HIV + vs. 5% of HIV- participants (p < 0.001). Among 8 HIV + participants with CD4 counts <200 cell/µL none had cleared their HPV infection during the study. CONCLUSIONS: Risk of oral HPV infection and persistence was significantly higher in HIV + adults with a history of poorly controlled HIV, which may put them at increased risk of HPV-associated cancer.


Assuntos
Alphapapillomavirus , Infecções por HIV , Doenças da Boca , Infecções por Papillomavirus , Adulto , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Doenças da Boca/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de Risco
3.
Econ Educ Rev ; 912022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37560092

RESUMO

Interventions to promote learning are often categorized into supply- and demand-side approaches. In a randomized experiment to promote learning about COVID-19 among Mozambican adults, we study the interaction between a supply and a demand intervention, respectively: teaching via targeted feedback, and providing financial incentives to learners. In theory, teaching and learner-incentives may be substitutes (crowding out one another) or complements (enhancing one another). Experts surveyed in advance predicted a high degree of substitutability between the two treatments. In contrast, we find substantially more complementarity than experts predicted. Combining teaching and incentive treatments raises COVID-19 knowledge test scores by 0.5 standard deviations, though the standalone teaching treatment is the most cost-effective. The complementarity between teaching and incentives persists in the longer run, over nine months post-treatment.

4.
Ann Thorac Surg ; 113(1): 118-124, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33662308

RESUMO

BACKGROUND: Infectious endocarditis is associated with substantial in-hospital mortality of 15%-20%. Effective management requires coordination between multiple medical and surgical subspecialties, which can often lead to disjointed care. Previous European studies have identified multidisciplinary endocarditis teams as a tool for reducing endocarditis mortality. METHODS: The multidisciplinary endocarditis team was formed in May 2018. The group developed an evidence-based algorithm for management of endocarditis that was used to provide recommendations for hospitalized patients over a 1-year period. Mortality outcomes were then retroactively assessed and compared to a historical control utilizing propensity matching. RESULTS: Between June 2018 and June 2019 the team provided guideline-based recommendations on 56 patients with Duke Criteria-definite endocarditis and at least 1 American Heart Association indication for surgery. The historical control included 68 patients with definite endocarditis and surgical indications admitted between July 1, 2014, and June 30, 2015. In-hospital mortality decreased significantly from 29.4% in 2014-2015 to 7.1% in 2018-2019 (P < .0001). There was a non-significant increase in the rate of surgical intervention after implementation of the team (41.2% vs 55.4%; P = 0.12). Propensity score matching demonstrated similar results. CONCLUSIONS: Implementation of a multidisciplinary endocarditis team was associated with a significant 1-year decrease in all-cause in-hospital mortality for patients with definite endocarditis and surgical indications, in the presence of notable differences between the 2 studied cohorts. In conjunction with previous studies demonstrating their effectiveness, these data support the idea that widespread adoption of endocarditis teams in North America could improve outcomes for this patient population.


Assuntos
Endocardite Bacteriana/cirurgia , Equipe de Assistência ao Paciente , Adulto , Idoso , Endocardite Bacteriana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão
5.
Ther Adv Infect Dis ; 8: 20499361211065596, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950478

RESUMO

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model. In this review, the authors will outline the steps they took to create and implement a successful multidisciplinary endocarditis team at the University of Michigan. In conjunction with existing data, this piece can be used as a resource for clinicians seeking to improve the care of patients with endocarditis at their institutions.

6.
J Nucl Cardiol ; 28(1): 289-294, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31485962

RESUMO

BACKGROUND: Multiple studies have demonstrated that when incorporated with conventional imaging modalities, cardiac F-18 PET/CT can aid in diagnosis of endocarditis and improve the sensitivity of the Duke Criteria. These studies used as their gold standard the opinion of an endocarditis team and were characterized by low percentages of patients who underwent surgery. We reviewed 4 years of surgically managed IE cases where F-18 cardiac PET/CT was used to aid diagnosis. METHODS: Between July 2014 and December 2018, we retrospectively reviewed 68 surgically managed endocarditis cases to identify patients who underwent pre-operative PET scans. RESULTS: Fourteen patients were identified who underwent F-18 cardiac PET/CT prior to surgical intervention. Nine cases were classified as possible endocarditis by Duke Criteria and 8 involved prosthetic valves. Twelve out of fourteen scans were interpreted as suggestive of or consistent with endocarditis based on FDG uptake. Twelve positive PETs were associated with either operative findings of infection and/or positive PCR testing on the excised valve. Two patients with negative scans were found to have non-infectious mobile masses intra-operatively, negative valve cultures and negative pathology. CONCLUSION: In a small cohort, F-18 FDG cardiac PET/CT correlated closely with intra-operative findings in patients with endocarditis and helped guide surgical decision-making. It could be considered for addition to the Duke Criteria in the American Heart Association endocarditis guidelines similar to European protocols.


Assuntos
Endocardite/diagnóstico por imagem , Endocardite/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Endocardite/microbiologia , Fluordesoxiglucose F18 , Humanos , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Estudos Retrospectivos
7.
Transpl Infect Dis ; 22(5): e13318, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32386104

RESUMO

Mycoplasma pneumoniae is one of the most common bacterial causes of pneumonia. Macrolide-resistant M pneumoniae (MRMP) was documented in 7.5% of isolates in the United States. Resistance portends poor outcomes to macrolide therapy, yet patients respond well to fluoroquinolones or tetracyclines such as minocycline. However, MRMP may be under-appreciated because M pneumoniae generally causes relatively mild infections in non-immunosuppressed adults that may resolve without effective therapy and because microbiological confirmation and susceptibility are not routinely performed. We report two cases of pneumonia due to MRMP in kidney transplant recipients. Both patients required hospital admission, worsened on macrolide therapy, and rapidly defervesced on doxycycline or levofloxacin. In one case, M pneumoniae was only identified by multiplex respiratory pathogen panel analysis of BAL fluid. Macrolide resistance was confirmed in both cases by real-time PCR and point mutations associated with macrolide resistance were identified. M pneumoniae was isolated from both cases, and molecular genotyping revealed the same genotype. In conclusion, clinicians should be aware of the potential for macrolide resistance in M pneumoniae, and may consider non-macrolide-based therapy for confirmed or non-responding infections in patients who are immunocompromised or hospitalized.


Assuntos
Mycoplasma pneumoniae , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae/efeitos dos fármacos
8.
Am J Med ; 133(1): 44-49, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521667

RESUMO

Infectious endocarditis is a highly morbid disease with approximately 43,000 cases per year in the United States. The modified Duke Criteria have poor sensitivity; however, advances in diagnostic imaging provide new tools for clinicians to make what can be an elusive diagnosis. There are a number of risk stratification calculators that can help guide providers in medical and surgical management. Patients who inject drugs pose unique challenges for the health care system as their addiction, which is often untreated, can lead to recurrent infections after valve replacement. There is a need to increase access to medication-assisted treatment for opioid use disorders in this population. Recent studies suggest that oral and depo antibiotics may be viable alternatives to conventional intravenous therapy. Additionally, shorter courses of antibiotic therapy are potentially equally efficacious in patients who are surgically managed. Given the complexities involved with their care, patients with endocarditis are best managed by multidisciplinary teams.


Assuntos
Antibacterianos/administração & dosagem , Endocardite/diagnóstico , Endocardite/terapia , Implante de Prótese de Valva Cardíaca , Administração Intravenosa , Administração Oral , Hemocultura , Procedimentos Cirúrgicos Cardíacos , Preparações de Ação Retardada , Ecocardiografia , Humanos , Equipe de Assistência ao Paciente , Tomografia por Emissão de Pósitrons , Recidiva , Medição de Risco , Abuso de Substâncias por Via Intravenosa/terapia
9.
Eur J Clin Microbiol Infect Dis ; 39(4): 735-739, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31838607

RESUMO

Infectious endocarditis is a highly morbid infection that requires coordination of care across medical and surgical specialties, often through the use of a multidisciplinary team model. Multiple studies have demonstrated that such conferences can improve clinical outcomes. However, little is known about physicians' impressions of these groups. We surveyed 126 (response rate of 30%) internal medicine, infectious diseases, cardiology, and cardiac surgery providers 1 year after the implementation of an endocarditis team at the University of Michigan. Ninety-eight percent of physicians felt that the endocarditis team improved communication between specialties. Additionally, over 85% of respondents agreed that the group influenced diagnostic evaluation, reduced management errors, increased access to surgery, and decreased in-hospital mortality for endocarditis patients. These results suggest that multidisciplinary endocarditis teams are valued by physicians as a tool to improve patient care and serve an important role in increasing communication between providers.


Assuntos
Atitude do Pessoal de Saúde , Endocardite , Equipe de Assistência ao Paciente , Médicos/psicologia , Humanos , Comunicação Interdisciplinar , Inquéritos e Questionários
10.
J Fungi (Basel) ; 5(3)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344869

RESUMO

Histoplasmosis is an endemic fungal infection that may affect both immune compromised and non-immune compromised individuals. It is now recognized that the geographic range of this organism is larger than previously understood, placing more people at risk. Infection with Histoplasma capsulatum may occur after inhalation of conidia that are aerosolized from the filamentous form of the organism in the environment. Clinical syndromes typically associated with histoplasmosis include acute or chronic pneumonia, chronic cavitary pulmonary infection, or mediastinal fibrosis or lymphadenitis. Disseminated infection can also occur, in which multiple organ systems are affected. In up to 10% of cases, infection of the central nervous system (CNS) with histoplasmosis may occur with or without disseminated infection. In this review, we discuss challenges related to the diagnosis of CNS histoplasmosis and appropriate treatment strategies that can lead to successful outcomes.

11.
SAGE Open Med ; 7: 2050312119851006, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205698

RESUMO

OBJECTIVES: Despite many advances in medicine, not all individuals with HIV are able to achieve complete virologic suppression. This retrospective study identifies variables associated with persistent HIV viremia in an academic clinic. METHODS: We studied 66 HIV-infected patients with a viral load of >200 copies/mL over 1 year, with controls matched 1:1 via a propensity score utilizing age at diagnosis, era of diagnosis, gender, and initial CD4 count. We collected data on multiple variables including medications, adherence, comorbidities, hospitalizations, and insurance status. Conditional logistic regression was used for unadjusted and adjusted analyses. RESULTS: A total of 66 viremic cases/matched controls were included. Fewer viremic patients were on antiretroviral therapy for all 12 months (45% vs 77%; odds ratio: 0.33, p = .018) and fewer were of white race (52% vs 70%; odds ratio: 0.49, p = .053). Hospitalization (11% vs 3%; odds ratio: 10, p = .028), underinsurance (20% vs 1%; odds ratio: 5.87, p = .022), and conflicting personal beliefs about their disease (17% vs 3%; odds ratio: 5.5, p = .027) were more common in viremic patients. Psychiatric illness increased the odds of viremia in patients who had four or more visits (odds ratio: 1.63/6.64 with four/five clinic visits, respectively). CONCLUSION: Psychiatric illness is an important contributor to the presence of persistent viremia in HIV-infected patients and deserves further study.

12.
Oper Neurosurg (Hagerstown) ; 16(5): E154-E158, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29905841

RESUMO

BACKGROUND AND IMPORTANCE: Neurocysticercosis (NCC) is an infectious helminthic disease often presenting in patients who have immigration or travel history from areas where NCC is endemic. Fourth ventricle cysts from NCC pose a unique treatment challenge, as there is little consensus on the best treatment. This case study describes the treatment of a patient with fourth ventricle neurocysticercosis (FVNCC), examines the therapeutic decision-making, and provides a video of a posterior fossa craniotomy (PFC) resection of a degenerative cyst. CLINICAL PRESENTATION: The patient presented with headache, dizziness, nausea, and memory difficulties. A fourth ventricle cyst consistent with NCC was found on magnetic resonance imaging, and serum enzyme-linked immunosorbent assay (ELISA) confirmed the diagnosis. The cyst was removed utilizing an open PFC followed by antihelminthic therapy and corticosteroids. There was resolution of symptoms at 9 mo postoperatively. CONCLUSION: Several treatment modalities have been proposed for isolated cysts in the fourth ventricle, including medication, ventriculoperitoneal shunt, endoscopic removal, and PFC. The treatment decision is complex, and there is little guidance on the best treatment choices. In this article, we describe treatment via PFC for an adherent FVNCC cyst.


Assuntos
Craniotomia/métodos , Quarto Ventrículo/diagnóstico por imagem , Quarto Ventrículo/cirurgia , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/cirurgia , Ventriculostomia/métodos , Adulto , Feminino , Seguimentos , Humanos
13.
Cell Rep ; 25(13): 3759-3773.e9, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590047

RESUMO

Long-lived reservoirs of persistent HIV are a major barrier to a cure. CD4+ hematopoietic stem and progenitor cells (HSPCs) have the capacity for lifelong survival, self-renewal, and the generation of daughter cells. Recent evidence shows that they are also susceptible to HIV infection in vitro and in vivo. Whether HSPCs harbor infectious virus or contribute to plasma virus (PV) is unknown. Here, we provide strong evidence that clusters of identical proviruses from HSPCs and their likely progeny often match residual PV. A higher proportion of these sequences match residual PV than proviral genomes from bone marrow and peripheral blood mononuclear cells that are observed only once. Furthermore, an analysis of near-full-length genomes isolated from HSPCs provides evidence that HSPCs harbor functional HIV proviral genomes that often match residual PV. These results support the conclusion that HIV-infected HSPCs form a distinct and functionally significant reservoir of persistent HIV in infected people.


Assuntos
Reservatórios de Doenças/virologia , Infecções por HIV/virologia , HIV-1/fisiologia , Células-Tronco Hematopoéticas/virologia , Viremia/virologia , Adulto , Idoso , Sequência de Bases , DNA Viral/genética , Genoma Viral , Células HEK293 , Infecções por HIV/sangue , HIV-1/genética , Humanos , Pessoa de Meia-Idade , Fases de Leitura Aberta/genética , Provírus/genética , Viremia/sangue , Vírion/fisiologia , Adulto Jovem
15.
JAMA ; 319(12): 1261-1268, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29584848

RESUMO

IMPORTANCE: About 40 000 Americans and 2 million people worldwide are newly infected with HIV each year. The combination antiretroviral regimen, tenofovir disoproxil fumarate (TDF)/emtricitabine, taken as a single pill once daily, has been shown to prevent HIV transmission but is used by fewer than 20% of people who could benefit in the United States. OBSERVATIONS: PubMed was searched on February 15, 2018, using the search terms pre-exposure, prophylaxis, HIV, and PrEP to identify English-language articles published between 2010 and 2018. Four placebo-controlled randomized clinical trials have demonstrated that preexposure prophylaxis (PrEP) with daily dosing of TDF/emtricitabine significantly reduces HIV acquisition in men who have sex with men, high-risk heterosexuals, and injection drug users who share injection equipment. The efficacy of daily TDF/emtricitabine exceeds 90% but is highly correlated with degree of adherence. TDF/emtricitabine is safe and well-tolerated. Only 2% of people discontinue PrEP because of adverse effects. Sexually transmitted infections are common among those using PrEP. Resistance to TDF/emtricitabine when used for PrEP is rare (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection who have false-negative findings on HIV antibody/antigen testing due to HIV infection acquired within 7 to 10 days of testing. Effective methods are needed to identify individuals at high risk for acquiring HIV, ensure their access to PrEP, and maximize medication adherence. CONCLUSIONS AND RELEVANCE: TDF/emtricitabine is an effective and safe therapy for preventing HIV transmission. Increasing prescription of TDF/emtricitabine for patients at risk of acquiring HIV has the potential to reduce new HIV infections.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Tenofovir/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Transmissão de Doença Infecciosa/prevenção & controle , Combinação de Medicamentos , Emtricitabina/efeitos adversos , Infecções por HIV/transmissão , Humanos , Fatores de Risco , Tenofovir/efeitos adversos
16.
Medicine (Baltimore) ; 97(13): e0245, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29595679

RESUMO

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.


Assuntos
Anfotericina B/uso terapêutico , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Fatores Etários , Anticorpos Antifúngicos/líquido cefalorraquidiano , Antígenos de Fungos/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Infecções Fúngicas do Sistema Nervoso Central/complicações , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Feminino , Histoplasmose/complicações , Histoplasmose/mortalidade , Humanos , Hospedeiro Imunocomprometido , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Espinal/efeitos dos fármacos
17.
Head Neck ; 39(12): 2433-2443, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28945296

RESUMO

BACKGROUND: We examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIV-positive head and neck cancer) and HIV negative (HIV-negative head and neck cancer). METHODS: Tissue microarrays (TMAs) were constructed using tumors from 41 disease site-matched and age-matched HIV-positive head and neck cancer cases and 44 HIV-negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables. RESULTS: Expression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIV-positive head and neck cancer, laryngeal disease site (P = .003) and Clavien-Dindo classification IV (CD4) counts <200 cells/µL (P = .01) were associated with poor prognosis. Multivariate analysis showed that p16 positivity was associated with improved overall survival (OS; P < .001) whereas increased expression of transforming growth factor-beta (TGF-ß) was associated with poor clinical outcome (P = .001). CONCLUSION: Disease site has significant effect on the expression of biomarkers. Expression of tumor TGF-ß could be a valuable addition to the conventional risk stratification equation for improving head and neck cancer disease management strategies.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/virologia , Soropositividade para HIV/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Casos e Controles , Causas de Morte , Terapia Combinada , Intervalo Livre de Doença , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Soropositividade para HIV/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Resultado do Tratamento
18.
PLoS Pathog ; 13(7): e1006509, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28732051

RESUMO

Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.


Assuntos
Antígenos CD4/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/fisiologia , Células-Tronco Hematopoéticas/virologia , Provírus/fisiologia , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Receptores de HIV/metabolismo , Adulto , Antígenos CD4/genética , Células Cultivadas , Feminino , Genoma Viral , Infecções por HIV/genética , HIV-1/genética , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Provírus/genética , Receptores CCR5/genética , Receptores CXCR4/genética , Receptores de HIV/genética , Adulto Jovem
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