Дисертації з теми "Latent HIV"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "Latent HIV".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Andrews, Sophie Marie. "Adaptive immune evasion in clinically latent HIV infection." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:b7416aab-d345-48df-9194-797c62d7db47.
Повний текст джерелаEsmail, Hanif. "How latent is 'latent' tuberculosis? : the radiographic, transcriptional and immunological characterisation of subclinical tuberculosis in HIV infected adults." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/30658.
Повний текст джерелаSILVA, NETO Francisco Bernardino da. "Teste tuberculínio no diagnóstico da infecção latente pelo Mycobacterium tuberculosis em pessoas vivendo com HIV/AIDS em um hospital de referência no Estado da Paraíba." Universidade Federal de Pernambuco, 2015. https://repositorio.ufpe.br/handle/123456789/17702.
Повний текст джерелаMade available in DSpace on 2016-08-18T14:35:26Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Bernardino_Versão_Final_13_04_2016VF_ATUAL (1).pdf: 1504145 bytes, checksum: 378eee47758feaa1664c834f3a789e0c (MD5) Previous issue date: 2015-08-20
O diagnóstico e o tratamento da infecção latente pelo Mycobacterium tuberculosis (ILTB) são indicados para grupos nos quais a prevalência da infecção latente é alta, em contactantes de casos novos de tuberculose (TB) e quando o risco de reativação é alto como em pessoas vivendo com HIV/AIDS (PVHA). Tanto o vírus da imunodeficiência humana (HIV) facilita a reativação da ILTB quanto o Mycobacterium tuberculosis contribui para a progressão da doença pelo HIV. O conhecimento acerca do diagnóstico e do tratamento da ILTB em PVHA torna-se fundamental visto que o Relatório Global de Controle da Tuberculose da Organização Mundial da Saúde (OMS) indica que as PVHA estão 26 a 31 vezes mais propensas a desenvolver TB ativa quando comparadas à população geral. Além disso, a taxa de letalidade da TB em PVHA é 3 vezes maior do que a observada na população geral. Apesar de suas limitações, o teste tuberculínico (TT) continua sendo a principal ferramenta de diagnóstico da ILTB, entretanto, isso não parece refletir no número de TT solicitados e realizados e, consequentemente, no número de tratamentos prescritos para ILTB. No Brasil, e em particular na Paraíba, os dados sobre a solicitação e realização do TT e acerca da prescrição do tratamento para ILTB são pouco conhecidos. Esse estudo objetivou verificar a frequência de solicitação e de realização (inoculação do derivado protéico purificado (PPD) e leitura) do TT, a frequência de TT reator e a frequência da prescrição do tratamento para ILTB e caracterizar as PVHA atendidas em serviço de referência em HIV/AIDS e TB no estado da Paraíba quanto a aspectos sociodemográficos e laboratoriais, no período de janeiro de 2009 a dezembro de 2013. Para obtenção dos dados, utilizou-se formulário padronizado, preenchido, retrospectivamente, a partir das informações contidas na primeira consulta registrada nos prontuários dos pacientes atendidos no período do estudo. Dos 3.191 pacientes incluídos na pesquisa, 2.303 (72,2%) tiveram o TT solicitado. Destes, 2.047 (89,0%) foram submetidos a realização do TT que compreendeu a inoculação do PPD e a leitura da induração. Dos 2.047 pacientes que tiveram o PPD inoculado e submetidos a leitura da induração, 90 (4,4%) pacientes tiveram o TT reator sendo o tratamento para ILTB prescrito para todos. Os resultados da pesquisa sugerem que há uma excelente adesão à solicitação do TT e à prescrição do tratamento para ILTB entre os profissionais médicos e baixa prevalência de ILTB no local do estudo. Outrossim, acessibilidade adequada para realização e boa compreensão por parte dos pacientes quanto a sua importância no contexto da atenção à saúde das PVHA garantiram a frequência elevada de realização do TT.
The diagnosis and treatment of latent infection with Mycobacterium tuberculosis (LIMTb) are given to groups in which the prevalence of latent infection is high, in contacts of new cases of tuberculosis (TB) and when the risk of reactivation is high as in people living with HIV/AIDS (PLHA). Both the human immunodeficiency virus (HIV) facilitates the reactivation of LIMTb as Mycobacterium tuberculosis contributes to the progression of HIV disease. The knowledge about the diagnosis and treatment for PLHA in LIMTb becomes critical as the Global Tuberculosis Control Report of the World Health Organization (WHO) indicates that PLHA are 26-31 times more likely to develop active TB compared the general population. In addition, the TB mortality rate PLHA is 3 times higher than that observed in the general population. Despite its limitations, the tuberculin skin test (TST) remains the primary diagnostic tool LIMTb, however, this does not reflect the number of TST ordered and carried out and, consequently, the number of prescription treatments for LIMTb. In Brazil, particularly in Paraiba, data on the application and realization of TST and for prescribing treatment for LIMTb are little known. Thus faces, this study aimed to verify the request frequency and achievement (inoculation of purified protein derivative (PPD) and reading of induration) of TST, the TST frequency of reactor and the frequency of prescription treatment for LIMTb and characterize the PLHA met in reference service on HIV/AIDS and TB in the state of Paraiba as the sociodemographic and laboratory aspects, from January 2009 to December 2013. To obtain the data, we used standardized form filled out retrospectively from information contained on the first visit recorded in the medical records of patients seen during the study period. Of the 3,191 patients included in the study, 2,303 (72.2%) had the TST requested. Of these, 2,047 (89.0%) underwent TST understood that inoculation of the PPD and the reading of induration. Of the 2,047 patients who had the PPD inoculated and subjected to reading of induration, 90 (4.4%) patients had TST reactor being treating LIMTb prescribed for everyone. The survey results suggest there is excellent adhesion to the request of the TST and prescription treatment for LIMTb among medical professionals and low prevalence of LIMTb in the study site. Likewise sufficient access for achievement and good understanding by patients and their importance in the context of attention to health of PLHA ensured the high frequency of TST realization.
Hiener, Bonnie. "Genetic Characterisation of Persistent HIV-1 in Naïve and Memory CD4+ T-cells from Effectively Treated Individuals." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29533.
Повний текст джерелаAntunes, Aline Araújo. "Vigilância da Tuberculose Latente nas pessoas que vivem com HIV/aids em Ribeirão Preto - SP, 2012 e 2013." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/22/22133/tde-15022016-161844/.
Повний текст джерелаTB is the main opportunistic infection to affect people living with HIV/AIDS (PLWHA), and TB/HIV coinfection is a major challenge for health systems. The study aimed to describe the monitoring of latent TB in PLWHA followed by HIV/AIDS Specialized Health Services Specialized (SHS) of Ribeirão Preto-SP, in the years 2012 and 2013. It was an epidemiological descriptive study. Were included 33 individuals who developed diagnosis of latent tuberculosis in 2012 and 2013, reported in the System Information \"TB chemoprophylaxis,\" and living with HIV/AIDS, followed by the five SHS municipal public health network of Ribeirão Preto-SP. For data collection, it was initially conducted a survey of PLWHA diagnosed with latent tuberculosis, from the number of individuals registered in the information system (IS) \"TB chemoprophylaxis.\" After, it was used a structured questionnaire containing 30 questions which were considered the following sections: I - Socio-demographic data; II - Data on the clinical profile of PLWHA - at diagnosis of latent TB; III - Data on the control of TB in PLWHA; IV Data on the situation, monitoring strategies and the outcome of latent TB in PLWHA. The study was developed from secondary sources of information: Information System \"TB chemoprophylaxis\"; Health Record; Computerized Hygia-Web system and Notifiable Diseases Information System (SINAN). As a complement, with the support of a particular script we interviewed the key actor - Municipal Program Coordinator for Tuberculosis Control and STD/AIDS - in order to characterize the scenario focusing on the description of the actions about prevention and control of TB in PLWHA. Data analysis was performed using descriptive statistics technique. Of the 355 cases identified in the IS chemoprophylaxis TB, 135 were reported in 2012 and 220 in 2013, with 44 occurrences involving PLWHA in the follow-up in the municipal public health system, of which 21 (47.7%) belonged to the SHS \"C\". Eleven cases were excluded due to non-location clinical records and errors in the classification of individuals who did not have the diagnosis of HIV/AIDS. Of the 33 PLWHA considered in the final study sample, there was a predominance of males (54.5%), aged 31-60 years (72.7%), economically active and married/common-law marriage (36.4%). Regarding the clinical profile, 75.8% had AIDS as a diagnostic situation, made use of ART, but only 30.3% had monthly removal of records of such drugs. The protective cell count (CD4 +) and viral load indicated stabilization of HIV/AIDS in most subjects. As for the control and outcome of QT, the majority (93.9%) of patients held in the self-administered treatment modality, with 22 (66.7%) completed the treatment but there was a dropout rate of 18.1 %. TB being the main opportunistic disease to affect and be responsible for more deaths associated with PLWHA, it is essential to implement strategies that enhance the surveillance of latent TB in PLWHA contributing as a key measure to control active disease. Surveillance data contribute to the planning and improvement of actions and interventions provided. So challenges are launched with regard to the integration of both programs forward the importance of surveillance and management of diseases in the context of public policy
Ranganath, Nischal. "Oncolytic Viruses as a Potential Approach to Eliminate Cells That Constitute the Latent HIV Reservoir." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37355.
Повний текст джерелаFong, Linda Ellen. "Data-Driven Analysis of Phospho-Signaling Network Responses Enables Latent HIV Infected T Cell Targeting." Thesis, Yale University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10957324.
Повний текст джерелаViral latency remains the most significant obstacle to HIV eradication. Current clinical strategies aim to purge the latent CD4+ T cell reservoir by activating viral expression, but are undercut by the inability to clear the latent reservoir. We first evaluated co-drugging criteria in a quantitative manner to optimize viral expression. However, this approach faces many challenges; and thus, we proposed to identify and target dysregulated signaling pathways in latent HIV-infected cells to promote cell death as a novel approach for eradication. To identify how HIV latency and reactivation alter signal transduction pathways regulating cell death, we explored the acute signaling response of latent HIV-infected CD4+ T cells across in vitro human latency models using systems-level analyses. We measured phosphorylation of five signaling proteins (AKT, IKBa, ERK, p38, and JNK) after stimulation with T-cell activating agents or latency reversing agents in infected cells and uninfected cells. Using these phosphorylation signatures, we built data-driven statistical models that successfully classified infected and uninfected cells, demonstrating that latent infection alters signaling at a systems level. We further identified that the stress kinase pathways p38 and JNK exhibited elevated signaling in latently infected cells and could be targeted to specifically increase cell death, independent of HIV reactivation.
To work out the mechanisms by which latent and reactivating HIV alters cell death regulation, we further examined signaling of 31 proteins in single cells over 48 hours using mass cytometry. Mass cytometry provides measurements at single-cell resolution, enabling us to separate responses in cells with latent versus reactivating HIV based on viral expression. We used conditional density-based analysis of the single-cell data to quantify the strength of signaling activity along different pathways. We discovered that latent and HIV-expressing cells are sensitized to apoptotic cell death via activation of p38-p53 signaling and inhibition of AKT/mTOR signaling. We identified a novel interaction in infected cells, in which increased p38 signaling activates the pro-death activity of the protein BAD, leading to increased apoptosis. Finally, we show in vitro that p38 and AKT/mTOR pathways can be simultaneously targeted to deplete the latent reservoir by preferentially killing latently infected cells without viral activation. Overall, we demonstrate that targeting altered phosphorylation signatures of latent HIV-infected cells provides a novel and effective strategy for latent HIV eradication.
Kunze, Christine [Verfasser], and Ruth [Akademischer Betreuer] Brack-Werner. "Strategien zur Inhibierung der HIV-Reaktiverung in latent infizierten Astrozyten / Christine Kunze ; Betreuer: Ruth Brack-Werner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1150159189/34.
Повний текст джерелаValencia, Celina I., and Celina I. Valencia. "Modeling social factors of HIV risk in Mexico." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/625554.
Повний текст джерелаO'Loughlin, Christina. "Evaluation of measurement quality in the assessment of health related issues using structural equation modelling techniques." Thesis, University of Ulster, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342424.
Повний текст джерелаMatsui, Hiroyuki. "CAGE-seq reveals that HIV-1 latent infection does not trigger unique cellular responses in a Jurkat T cell model." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/265190.
Повний текст джерелаPicone, Camila de Melo. "Avaliação da taxa de acesso à prescrição médica do tratamento preventivo de tuberculose com isoniazida em serviço especializado de HIV/aids." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-02062014-153526/.
Повний текст джерелаBackground: Isoniazid Preventive Treatment (IPT) is recommended for patients with HIV/AIDS and Latent Infection by Mycobacterium tuberculosis (ILMTb) and no contraindication to isoniazid. However, access barriers may prevent patients to undergo to this treatment. Objectives: This study evaluated the rate of access to the prescription of IPT in subjects with HIV/aids and ILMTb followed up in a specialized HIV/aids from February 2005 to December 2009. For subjects who did not have access to the prescription of IPT, we sought, on records, justification for this conduct. Also, the epidemiological, clinical and demographic profile of individuals with HIV/AIDS and ILMTb and the characteristic of the doctor who requested the tuberculin skin test (TST) and prescribed IPT were identified. Methods: from 02 February 2005 to 31 December 2009 subjects followed up at SEAP HIV/aids with HIV/aids and ILMTB, diagnosed by Tuberculin Test (TST) were included. Information was collected from the medical records and from the Hospital Information and Management System (SIGH) - Pharmacy Module. Results: 238 subjects were included, among the 310 who had TST > 5 mm during the study period. Of these, 70.6 % (168) were male and the average age was 42.6 years, 88.2 % (210) had access to the prescription of IPT. Access to IPT prescription was associated with age , size of response to TST, nadir of lymphocytes CD4 + in subjects on ART and presence of BCG scar: younger subjects with response to TST equal to or greater than 10 mm and BCG scar had higher access rate to IPT prescription. An issue to be explored in the future refers to variables that influence the professional\'s decision to prescribe this treatment when it is technically recommended. Conclusion: younger subjects with better immune status at baseline, greater response to TST and presence of BCG scar, had more access to IPT. This study highlighted the need of educational programs for health professionals, in order to improve the coverage of activities devoted to reduce morbidity and mortality in HIV/aids patients, as is the treatment of ILMTB, recommended in national tuberculosis and HIV/AIDS programs. Furthermore, it is crucial, for interdisciplinary health teams, to operate in an integrated and harmonious way, to ensure, for HIV/aids patients, a healthy and longer life
Devlin, Kathryn Noel. "EMPIRICALLY IDENTIFIED NEUROPSYCHOLOGICAL SUBTYPES IN HIV INFECTION: IMPLICATIONS FOR ETIOLOGY AND PROGNOSIS." Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/521261.
Повний текст джерелаPh.D.
Heterogeneity in the profile of HIV-associated neuropsychological disorder (HAND) may obscure understanding of its etiology and prognosis. Despite longstanding acknowledgement of this heterogeneity, HAND diagnostic approaches such as the Frascati criteria characterize neuropsychological function based on the level of impairment, without regard to the pattern of strengths and weaknesses. Attention to these patterns may enhance etiologic and prognostic specificity. We used latent class analysis (LCA) to identify relatively homogeneous subtypes of neurocognitive function in adults with well-treated HIV infection. We compared the diagnostic agreement of latent classes and Frascati categories, as well as their associations with demographics, HIV markers and antiretroviral factors, comorbid medical and psychiatric conditions, and everyday functioning. LCA identified four classes, whose cognitive profiles are depicted in Figure 1: cognitively intact, mild-to-moderate motor/speed impairment, mild-to-moderate memory/visuoconstruction impairment, and moderate mixed impairment. Latent classes and Frascati categories demonstrated good agreement in the overall classification of impaired cognition but more disagreement regarding subtypes of impairment. Both latent classes and Frascati categories demonstrated unique associations with etiologic factors and significant associations with functional outcomes. However, only latent classes, not Frascati categories, were associated with HIV variables. Additionally, functional difficulties were significantly elevated in the motor impairment class but not the memory impairment class despite similar levels of cognitive impairment in the two groups. Findings support the utility of a diagnostic approach that accounts for both the level and pattern of neurocognitive impairment. Future research should examine the neuropathological mechanisms, longitudinal trajectories, and treatments of empirically identified HAND subtypes.
Temple University--Theses
Bouchat, Sophie. "Etude de la levée de la latence du virus HIV-1 et du potentiel thérapeutique associé." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209220.
Повний текст джерелаReuse, Sophie. "Etude de la réactivation de l'expression des provirus HIV-1 latents par la prostratine en synergie avec des inhibiteurs de désacétylases: mécanismes moléculaires impliqués et potentiel thérapeutique." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210213.
Повний текст джерела\
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Finestone, Michelle. "An Evaluation of a theory-based support group intervention for children affected by maternal HIV / Aids." Thesis, University of Pretoria, 2013. http://hdl.handle.net/2263/40207.
Повний текст джерелаThesis (PhD)--University of Pretoria, 2013.
gm2014
Educational Psychology
unrestricted
Herzer, ThaÃs LÃbo. "InfecÃÃo latente por mycobacterium tuberculosis em portadores de infecÃÃo por HIV/AIDS: anÃlise atravÃs do uso de teste tuberculÃnico e teste de liberaÃÃo de interferon-gama." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=7821.
Повний текст джерелаPeople living with HIV have an enhanced chance to develop and to die of tuberculosis (TB). Many studies demonstrate that chemoprophylaxis for latent tuberculosis infection (LTBI) reduces the progression to active TB. Indeed, the diagnosis of LTBI is controversial. In Brazil, the only test approved for use is the tuberculin skin test (TST), however, this test is complicated by several problems due to application and interpretation of the exam. Recently developed interferon-gamma release assays (IGRA) using Mycobacterium tuberculosis-specific antigens have the advantage of decreased cross-reactivity and, therefore, increased specificity. The purpose of this study is to evaluate the adherence of LTBI diagnosis and to compare the results of the QuantiFERON-TBÂ Gold In-Tube test (QTF-GIT) and TST in a population of HIV-positive individuals from a country with high prevalence of TB. A cross-sectional study was carried out with 351 HIV patients without active tuberculosis, attending outpatient in two reference centers, from November 2007- 2010. At admission, 41.8% had realized TST, 36.3% had been interrogated about TB exposure and 28.4% had performed a chest X-ray. Chemoprophylaxis was offered to 73.3% of TST positive patients. The TST and QTF-GIT results were positive in 25.3% and 6.7% (p<0.001) of the individuals, respectively. The agreement between the two tests was poor (k= -0.037). Drug use (OR 7, 95% CI 1.5-32.1; p=0.01), TB exposure (OR 13, 95% CI 2.7-62.83; p=0.001), previous LTBI prophylaxis (OR 17.5, 95% CI 3.4-90.4; p<0.001), and living outside the state capÃtal (OR 2.7, 95% CI 1-7.2; p= 0.04) were associated with a positive TST result. There is no association between QTF-GIT positive result and risk factors for TB. TST positive individuals had a higher mean CD4+ cell count than those with TST negative result (535.8 cell/mm3 vs. 373.4 cell/mm3; p=0.006), in contrast to QTF-GIT positive result (277 cell/mm3 vs. 438.3 cell/mm3; p= 0.055). Higher viral load was associated with QTF-GIT positive result (4.8 log10 cop/ml vs. 2.1 log10 cop/ml; p= 0.005). Despite of Brazil being a country with a high burden of TB, more than half the patients have not realized TST, which appears to be more sensitive than QTF-GIT for diagnosis of LTBI. Otherwise, QTF-GIT shows better results in patients with advanced immunosuppression and high viral load. We suggest the use of both tests to increase LTBI diagnosis and decrease the risk of disease progression.
Wyndham-Thomas, Chloe. "Screening for latent M. tuberculosis infection in HIV-positive patients residing in low tuberculosis incidence settings: Investigation of the current practices and identification of clinical- and immune-based strategies for improvement." Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/241270.
Повний текст джерелаDoctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
Roberts, Jocelyn. "Behavioural beliefs concerning gender and high-risk sexual behaviours in the context of HIV/AIDS in PNG : views from within teacher education." Thesis, Queensland University of Technology, 2012. https://eprints.qut.edu.au/54675/1/Jocelyn_Roberts_Thesis.pdf.
Повний текст джерелаBrookmeyer, Kathryn Amanda. "Disentangling Pathways of Adolescent Sexual Risk from Problem Behavior Syndrome." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/psych_diss/32.
Повний текст джерелаJaafoura, Salma. "Mémoire lymphocytaire T et persistance virale." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114847.
Повний текст джерелаDuring the primary immune response, CD8 memory emerges from an environment of strong immune activation. The FoxP3 regulatory CD4 T-cell subset (Treg) is known as a key suppressive component of the immune system. We report that Tregs are required for the generation of functional CD8 memory. In the absence of Tregs during priming, the resulting memory cells proliferate poorly and fail to differentiate into functional cytotoxic secondary effectors following antigen reactivation. We find that the Tregs act early, during the expansion phase of primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory precursors. This crucial new role of Tregs has implications for optimal vaccine development. In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4 T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. We provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory).This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the TSCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies
Vasconcelos, Ludmila Moreira. "Tratamento de tuberculose latente: um desafio para o controle da doença." Faculdade de Medicina de São José do Rio Preto, 2017. http://hdl.handle.net/tede/441.
Повний текст джерелаMade available in DSpace on 2018-10-31T18:37:25Z (GMT). No. of bitstreams: 1 LudmilaMoreiraVasconcelos_dissert.pdf: 1613747 bytes, checksum: af77415c21324e1dbbeddf59d74195ea (MD5) Previous issue date: 2017-04-17
early detection of latent tuberculosis infection is one of the TB control strategy recommended by the World Health Organization. Objective: to analyze the association of latent tuberculosis infection with sociodemographic, clinical and risk factors for active TB cases chemoprophylaxis. Material and Methods: A retrospective cross-sectional epidemiological study, based on secondary data chemoprophylaxis notification form of tuberculosis of the state information system (TBWEB) of Epidemiological Surveillance Group XXIX (GVE 29) of São José do Rio Preto. They considered all reported cases from 2009 to 2013. The selected variables were sociodemographic and clinical. For the analysis, all statistical tests were applied with a 0.05 significance level. The software used for analysis were Minitab® 17 (Minitab Inc.) and Statistica 10 (StatSoft Inc.). Results: predominance of females, mean age 37.51 years and median of 40.00 years. Smear the day with negative sputum was associated significantly with cough (P = 0.001) and occupation (P <0.001). Few HIV / AIDS and health care professionals made the smear and sputum culture. Conclusion: The study found it hard both in screening latent tuberculosis, as in diagnosis and treatment, which may contribute to the spread of TB and multidrug resistance, increasing the morbidity and mortality rates from the disease, particularly among co-infected with HIV.
a detecção precoce da tuberculose infecção latente é uma das estratégias de controle da tuberculose recomendada pela Organização Mundial de Saúde. Objetivo: analisar a associação da tuberculose de infecção latente com variáveis sociodemográficas, clínicas e fatores de risco para tuberculose ativa de casos de quimioprofilaxia. Material e Método: estudo epidemiológico transversal retrospectivo, a partir de dados secundários da ficha de notificação de quimioprofilaxia da tuberculose do sistema de informação estadual (TBWEB) do Grupo de Vigilância Epidemiológica XXIX (GVE 29) de São José do Rio Preto. Foram considerados todos os casos notificados de 2009 a 2013. As variáveis selecionadas foram as sociodemográficas e clínicas. Para a análise, todos os testes estatísticos foram aplicados com nível de significância de 0,05. Os softwares utilizados para análise foram o Minitab® 17 (Minitab Inc.) e Statistica 10 (StatSoft Inc.). Resultados: predomínio do sexo feminino, idade média 37,51 anos e mediana de 40,00 anos. Realização da baciloscopia com resultado negativo do escarro se associou de forma significativa com a tosse (P=0,001) e ocupação (P<0,001). Poucos portadores de HIV/Aids e profissionais de saúde realizaram a baciloscopia e cultura do escarro. Conclusão: O estudo mostrou dificuldades tanto no rastreio de tuberculose infecção latente, como no diagnóstico e tratamento, o que pode contribuir para a multirresistência e disseminação da TB, aumentando as taxas de morbimortalidade pela doença, principalmente entre os coinfectados pelo HIV.
Dahabieh, Matthew Solomon. "Regulation of HIV-1 latency by basal transcription." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44153.
Повний текст джерелаSantos, Danielle Talita dos. "Prova tuberculínica e infecção latente das tuberculose entre indivíduos com HIV/AIDS." Universidade Estadual de Londrina. Centro de Ciências da Saúde. Programa de Pós-Graduação em Enfermagem, 2013. http://www.bibliotecadigital.uel.br/document/?code=vtls000188990.
Повний текст джерелаTuberculosis is an important cause of mortality among individuals with HIV/AIDS. Tuberculin skin test (TST) is a test used as a diagnostic tool that identifies the Latent Tuberculosis Infection (LTBI) and thus allows prophylactic treatment. People with HIV/AIDS are part of groups that are under the recommendation of periodical PT and treatment of LTBI in order to prevent their illness. The aim of this study was to analyze the frequency of application of the tuberculin test in individuals with HIV / AIDS , as well as the prevalence and outcome of cases of latent TB infection . Retrospective cohort study with a quantitative approach, performed in the Reference Center paw tuberculosis and AIDS (RC) in the city of Londrina-PR. The study population consisted of 880 patients who underwent TST between 2003 and 2010 with registration in the Book of the PT Clinic of Pulmonology. The data were completed using patient charts and records of the Information System for Notifiable Diseases, reported through December 2012. Data were tabulated using SPSS 20.0 program for statistical analysis and t test in normally distributed variables and Mann-Whitney test those without normal distribution. To assess the association between variables we used the chi-square and Fisher's exact test and a significance level of 5%. A loss of 113 records and sample comprised 767 patients, of whom 69 (9.0 %) never had read the TBST. Among the 698 cases who completed the TBST, the positivity was 9.5 %. 1172 examinations were performed in the study population, resulting in an average of 1.52 TBST requested and 1.32 TBST held (with reading) per patient, compared with an average follow-up time of 7.7 years in RC. We observed statistically significant association between a positive TBST and male, the same occurring with housing / prison , considering that 41.7 % of prisoners had TST results reactor. Among the 66 cases with positive TBST, 53 (80.3 %) were characterized as LTBI, thus indicating treatment, of whom 39 (73.6 %) started treatment and 10 (25.6 %) left the treatment. We observed statistically significant association between higher CD4 + counts (> 201 cells/mm3) and reactivity to TBST. We identified 58 (7.5 %) cases of tuberculosis, among these, 22.4 % abandoned treatment. Regarding the 21 cases of deaths 9.5% were associated with TB. Adherence to the realization of TBST and treatment of LTBI has been difficult job. Should strengthen health policies aimed at strengthening access to and monitoring of patients with concomitant sensitization and training of professionals, to increase the use of TBST in individuals with HIV / AIDS. Noncompliance with treatment of LTBI and TB as indicated was handsome; situation reinforces the need for further supervision and control of patients requiring this therapy aimed at improving the health of these individuals.
Friedman, Julia H. "HIV-1 Latency as a Consequence of Chromatin Regulation." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301495389.
Повний текст джерелаTong, Phuoc Bao Viet. "Développement d’une nouvelle classe d'agents de sortie de latence du VIH-1." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT009.
Повний текст джерелаDespite its efficiency to prevent viral multiplication, antiretroviral therapy (ART) is unable to cure patients with HIV-1. Indeed, if ART is stopped, a viral rebound is observed. This increase in blood viral load is due to the activation of HIV-1 reservoirs, among which latently-infected memory CD4+ T cells. These cells are rare (1-10 per million of quiescent T cells), appear very quickly following infection and have a long half-life (almost 4 years). To purge this long-lived reservoir the "Shock and Kill" (or kick and kill) approach was developed. This strategy relies on the use of latency reversing agents (LRAs) to induce reservoir activation. All LRAs developed until now target cellular proteins such as histone deacetylases or protein kinase C. These LRAs did not affect the reservoir size of HIV+ patients.Here we present a new LRA family that binds to and activates an HIV-1 protein. These compounds were identified by in silico screening, are not cytotoxic and affect the biological activity of their target. They were less efficient than available LRAs on HIV-1 latent cell lines. Nevertheless, when tested on latent T-cells from HIV-1 patients in ex vivo assays, the lead compound D10 at 50 nM was ~ 80% more efficient than bryostatin-1, one of the best LRA available to date.Using a chemoinformatic approach, we selected 11 analogs of D10, termed N1 to N11. Some of these analogs (N5, N8) showed a stronger effect than D10 on latent cell lines. The study of this family enabled us to elaborate a structure/ function relationship.We thus identified a new family of HIV latency reversing agents targeting a viral protein and that should therefore be more specific than LRAs that target cellular proteins
Lam, Cindy. "Effects of APOBEC3-Induced Mutations on HIV-1 Expression and Latency." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39811.
Повний текст джерелаSouza, Josiane Maria Oliveira de. "Prova tuberculínica e QuantiFERON-TB Gold in-Tube na identificação da infecção latente pelo Mycobacterium tuberculosis em pessoas vivendo com AIDS." reponame:Repositório Institucional da UnB, 2014. http://repositorio.unb.br/handle/10482/17390.
Повний текст джерелаSubmitted by Larissa Stefane Vieira Rodrigues (larissarodrigues@bce.unb.br) on 2014-12-10T12:32:26Z No. of bitstreams: 1 2014_JosianeMariaOliveiraDeSouza.pdf: 2060736 bytes, checksum: 74e9755ce2457d801f6c6bd192611376 (MD5)
Approved for entry into archive by Raquel Viana(raquelviana@bce.unb.br) on 2014-12-16T19:32:07Z (GMT) No. of bitstreams: 1 2014_JosianeMariaOliveiraDeSouza.pdf: 2060736 bytes, checksum: 74e9755ce2457d801f6c6bd192611376 (MD5)
Made available in DSpace on 2014-12-16T19:32:07Z (GMT). No. of bitstreams: 1 2014_JosianeMariaOliveiraDeSouza.pdf: 2060736 bytes, checksum: 74e9755ce2457d801f6c6bd192611376 (MD5)
A tuberculose (TB) é a mais freqüente e fatal doença oportunista em pessoas vivendo com HIV/aids (PVHA), em função do maior risco de seu desenvolvimento após a infecção pelo Mycobacterium tuberculosis. O diagnóstico e tratamento da infecção latente pelo Mycobacterium tuberculosis (ILTB) na PVHA é fundamental para evitar a progressão para doença e morte por TB. O presente estudo tem por objetivo analisar o uso dos testes Prova Tuberculínica (PT) e QuantiFERON-TB Gold in-Tube (QTF-GIT) na identificação da ILTB em pessoas vivendo com aids. A pesquisa utilizou os modelos epidemiológicos do tipo transversal, série de casos e estudo de caso. A amostra consistiu de 300 pacientes com HIV/aids, selecionados em oito serviços de assistência especializados em DST/HIV/aids do Distrito Federal, entre 2011 e 2013, com seguimento até maio de 2014. A análise dos dados transversais revelou uma média de CD4 de 477,5células/mm³, sendo que 18 pacientes (6%, IC95%:3,6-9,3) apresentaram ILTB a partir do resultado positivo da PT e/ou QTF-GIT. Destaca-se que quatro pacientes (1,3%, IC95%:0,04-2,63) apresentaram uma PT positiva e oito pacientes (2,7%, IC95%:0,8-4,5) apontaram para o teste QFT-GIT positivo, sendo que seis pacientes (2%, IC95%:0,4-3,6) obtiveram resultados positivos para ambos os testes – aumento de 81,8% na detecção de ILTB pelo QFT-GIT em relação à PT. A concordância entre os dois testes foi de 96% (kappa=0,48). Do total de casos, 295 pacientes (98,3%) utilizavam terapia antirretroviral. No seguimento, dezessete pacientes foram identificados com ILTB (5,1%), sendo que doze casos (70,6%) realizaram a terapia preventiva com isoniazida (TPI) – nenhum destes adoeceu por TB. A média de proteção após a TPI foi de 495,4 dias para QTF-GIT+ e de 540 dias, a PT≥5mm. Os resultados revelaram baixa prevalência de ILTB a partir dos resultados da PT e QTF-GIT na referida população em cenário de baixa carga da TB e média renda, o que limitou a capacidade de avaliar os fatores preditores associados aos resultados positivos dos testes. Na população com imunossupressão moderada houve melhor resposta ao QTF-GIT do que a PT, para detecção da ILTB. No seguimento dos casos identificaram-se dois casos de TB pulmonar entre os pacientes com resultado negativo do QTF-GIT e PT, com atipia na apresentação clínica e laboratorial, além de boas condições socioeconômicas e moderada contagem de CD4, o que demonstrou que mesmo com uso adicional de um teste, não foi possível identificar e tratar todos os pacientes com risco de desenvolvimento da TB entre as PVHA. O único óbito ocorrido no estudo não foi relacionado à TB. Concluiu-se que é preciso a execução de demais estudos que avaliem outros fatores de risco e biomarcadores para ILTB entre as PVHA, mesmo diante dos resultados negativos, além da necessidade de maior tempo de seguimento para avaliar a durabilidade da proteção pela isoniazida e de estudos que explorem a relação custoefetividade do uso do QTF-GIT entre as PVHA. _________________________________________________________________________________ ABSTRACT
Tuberculosis (TB) is the most frequent and fatal opportunistic infection in people living with HIV/AIDS (PLWHA), due to the higher risk of developing TB after infection with Mycobacterium Tuberculosis. Hence, the diagnosis and treatment of latent Mycobacterium Tuberculosis infection (LTBI) in PLWHA is essential to prevent disease progression and death from TB. The study aims to analyze the use of two tests Tuberculin skin testing (TST) and QuantiFERON-TB Gold In-Tube (QTF-GIT) in the identification of LTBI in people living with AIDS. Used the cross-sectional epidemiological models, case series and case study. The sample consisted of 300 patients with HIV/AIDS of the Federal District, between 2011 and 2013, with follow-up through May 2014 the analysis of cross-sectional data revealed in the average CD4 count of 477.5 cells/mm ³ and 18 patients (6%, 95% CI: 3.6-9.3) had LTBI positive result from the TST and/or QTF-GIT. Four patients (1.3%, 95% CI: 0.042.63) had a positive TST-eight (2.7%, 95% CI: 0.8-4.5) tested positive QFT-GIT, and six (2%, 95% CI 0.4-3.6) had positive results for both tests. That is, a relative increase of 81.8% in detecting LTBI by QTF-GIT compared to the TST. The agreement between the two tests was 96% (kappa =0.48). Of the total cases, 295 patients (98.3%) were using antiretroviral therapy. Following seventeen patients were identified with LTBI (5.1%), while 12 cases (70.6%) underwent isoniazid preventive therapy (IPT), and among them, none became ill with TB. The average protection after IPT was 495.4 days for QTF-GIT + and 540 days, TST≥5mm. The results showed a low tuberculosis burden and middle income, which limited the ability to assess the predictive factors associated with positive test results scenario. Individuals with moderate immunosuppressant responded better to QTF-GIT than the TST, to detect LTBI. Following the cases, there were limitations in identifying all patients susceptible to developing TB. During follow-up there were two cases of Pulmonary tuberculosis among patients with negative results of QTF-GIT and TST, with atypical in clinical and laboratory presentation, but good socioeconomic conditions and moderate CD4 count. What has shown that even with the additional use of a diagnostic test was not possible to identify and promptly treat all patients with HIV/AIDS at risk of developing TB. The only death in the study was not related to tuberculosis. Finally, we suggest further studies that assess other risk factors and biomarkers for LTBI among PLWHA, despite the negative results. Besides being required longer follow-up to evaluate the durability of protection by isoniazid and studies exploring the cost-effectiveness of using QTF-GIT among PLWHA relationship. _________________________________________________________________________________ RESUMEN
La tuberculosis (TB) es la enfermedad oportunista más frecuente y fatal en personas que viven con VIH/sida (PVVS), en función del mayor riesgo de desarrollar TB después de infección por Mycobacterium tuberculosis. Por consiguiente, el diagnóstico y tratamiento de la infección latente por Mycobacterium tuberculosis (ILTB) en las PVVS es fundamental para evitar la progresión a enfermedad y muerte por TB. El objetivo de este estudio es analizar el uso de dos pruebas, la Prueba Tuberculínica (PT) y QuantiFERON-TB Gold in-Tube (QTFGIT) en la identificación de la ILTB en personas que viven con el sida. Se utilizaran los modelos epidemiológicos de tipo transversal, serie de casos y estudio de caso. La muestra consistió en 300 pacientes con VIH/sida, seleccionados en ocho servicios especializados en ETS/VIH/sida del DF, entre 2011 y 2013, con seguimiento hasta mayo de 2014. El análisis de los datos transversales reveló un promedio de CD4 de 477,5 células/mm³ y 18 pacientes (6%, IC95%:3,6-9,3) tuvieran ILTB a partir del resultado positivo de la PT y/o QTF-GIT. Cuatro pacientes (1,3%, IC95%:0,04-2,63) presentaron una PT positiva y ocho (2,7%, IC95%:0,8- 4,5) la prueba QFT-GIT positiva y seis (2%, IC95%:0,4-3,6) tuvieron resultados positivos en las dos pruebas. Es decir, un incremento relativo de 81,8% en la detección de ILTB por el QFT-GIT en relación con la PT. La concordancia entre las dos pruebas fue de 96% (kappa=0,48). Del total de casos, 295 pacientes (98,3%) utilizaban terapia antirretroviral. Siguiente diecisiete pacientes fueran identificados con ILTB (5.1%) y 12 de estos casos (70.6%) se sometieron a la terapia preventiva con isoniazida (TPI), y, entre ellos, ninguno se enfermó de TB. La media de protección después de la TPI fue de 495,4 días para QTF-GIT+ y de 540 días, la PT≥5mm. Los resultados mostraron una baja prevalencia de ILTB a partir de los resultados de la PT y QTF-GIT en esa población en escenario de baja carga de tuberculosis y media renta, lo que limitó la capacidad de evaluar los factores predictores asociados a los resultados positivos de las dos pruebas. Los casos con inmunosupresión moderada respondieron mejor al QTF-GIT que a la PT, para detectar la ILTB. En el seguimiento de los casos, hubo limitación en la identificación de todos los pacientes susceptibles a desarrollar TB. Durante el seguimiento hubo dos casos de tuberculosis pulmonar entre los pacientes con resultado negativo del QTF-GIT y PT, con atipia en la presentación clínica y de laboratorio, además de buenas condiciones socioeconómicas y 13 moderado recuento de CD4. Lo que demostró que a pesar del uso adicional de una prueba diagnóstica no fue posible identificar y tratar tempranamente a todos los pacientes con VIH/sida en riesgo de desarrollar TB. La única muerte ocurrida en el estudio no estaba relacionada con la tuberculosis. Por último, se sugiere más estudios que evalúen otros factores de riesgo y biomarcadores para ILTB entre las PVVS, a pesar de los resultados negativos. Además de la necesidad de un mayor tiempo de seguimiento para evaluar la durabilidad de la protección por la isoniazida y de estudios que exploren la relación costo-efectividad del uso del QTF-GIT entre las PVVS.
Smutná, Katarína 1991. "Schlafen 12, a novel HIV restriction factor involved in latency." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/666297.
Повний текст джерелаEl proceso por el cual el virus de la Inmunodeficiencia Humana (VIH) establece y mantiene un estado de latencia no se conoce en su totalidad. La proliferación homeostática (HSP, de sus siglas en ingés “Homeostatic proliferation”) es uno de los mecanismos por el cual las células T CD4 “naive” y de memoria se mantienen in vivo. Además, HSP también contribuye al mantenimiento del reservorio de virus en forma latente. Además, las células T CD4 “naive” infectadas y cultivadas en condiciones de HSP no son capaces de reactivarse a diferencia de las células T CD4 de memoria activadas vía TCR. Estudios previos sugieren que esta observación se debe a un bloqueo post-transcripcional en células T “naive” cultivadas en condiciones de HSP. En esta tesis comparamos la perfil del transcriptoma de células T CD4 “naive” y de memoria. Entre los genes diferencialmente expresados que podrían participar en el proceso de latencia del VIH, identificamos Schlafen 12 (SLFN12) como un candidato interesante que podría ser un factor de restricción del virus. Los resultados de este trabajo muestran que SLFN12 establece un bloqueo post-transcripcional en células infectadas por VIH, y de esta forma inhibe tanto la producción del virus como su reactivación en células infectadas de forma latente. Estas observaciones pueden ser de gran ayuda para entender mejor los mecanismos subyacentes a la latencia del VIH así como su reactivación en células CD4 T “naive” mantenidas bajo condiciones de HSP. En su conjunto, estos resultados podrían contribuir al diseño de nuevas estrategias para erradicar el VIH.
Al, Ali Sally. "NOVEL APPROACHES FOR THE ERADICATION OF HIV LATENTLY INFECTED CELLS." Wright State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=wright1377374244.
Повний текст джерелаRodriguez, Ailin. "Cross-sectional Predictors of HIV Risk among Latino Migrant Workers." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3711.
Повний текст джерелаGreig, Matthew. "Characterization of HIV-1 Proviral Latency Induced Through APOBEC3 Mutagenesis and Reverse Transcriptase Error." Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/41078.
Повний текст джерелаNonodi, Thato Pearl. "NMR Metabonomics in an in vitro Model of HIV-1 latency." Diss., University of Pretoria, 2017. http://hdl.handle.net/2263/63280.
Повний текст джерелаDissertation (MSc)--University of Pretoria, 2017.
Technology Innovation Agency (TIA)
National Research Foundation (NRF)
Biochemistry
MSc
Unrestricted
Costiniuk, Cecilia T. "Oncolytic Viruses as a Potential Approach to Eliminate the HIV Reservoir." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23933.
Повний текст джерелаNorton, Nicholas James. "Cellular and viral factors affecting HIV-1 silencing and reactivation." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/290018.
Повний текст джерелаCristina, Rocha Vilela Moura Líbia. "Teste tuberculínico e tratamento da tuberculose latente em uma coorte de pacientes com HIV/AIDS." Universidade Federal de Pernambuco, 2011. https://repositorio.ufpe.br/handle/123456789/6988.
Повний текст джерелаA identificação de pessoas soropositivas com tuberculose latente (TBL), através do teste tuberculínico e o tratamento preventivo para tuberculose (TB), estão incluídas nas recomendações para a assistência aos pacientes com HIV/Aids em todo mundo. No Recife, entre julho de 2007 e fevereiro 2010, acompanhou-se uma coorte de pacientes HIV/Aids atendidos em dois serviços de referência - o Hospital Correia Picanço e o Hospital Universitário Oswaldo Cruz, com os seguintes objetivos: descrever a freqüência de realização do TT e analisar os fatores associados a sua não realização, assim como os fatores associados à sua positividade em pacientes infectados pelo HIV; estimar a probabilidade dos pacientes não reatores ao primeiro teste não repetirem o TT, analisar os fatores associados ao tempo até sua repetição e analisar a efetividade do tratamento para TBL com isoniazida (INH) 300mg/dia, por seis meses, controlando os co-fatores potenciais de confusão. No primeiro estudo realizou-se um caso controle onde a variável dependente foi a realização do TT. No segundo estudo utilizou-se o método de Kaplan-Meier para estimar a probabilidade da não repetição do TT e o teste de Log Rank para verificar se houve diferenças entre as estimativas do Kaplan Meier para as categorias de cada variável do estudo. No terceiro estudo acompanhou-se uma coorte de pacientes com indicação de realizar o tratamento para TBL. Calculou-se densidade incidência para quem foi exposto a INH e para quem teve indicação e não foi exposto à INH e a razão entre as taxas (Hazard Ratio). Estimou-se a probabilidade de não ter TB pelo método de Kaplan Méier. Os principais resultados encontrados foram: 2.290 pacientes entraram na coorte, 1.087 (47,5%) realizaram o TT e 1203 (52,5%) não realizaram. Estiveram associados a não realização do TT: sexo masculino, idade menor de 39 anos, menos de nove anos de escolaridade, ganhar mais que um salário mínimo, ser usuário de crack e ser atendido no Hospital Universitário Oswaldo Cruz. Entre os 1.087 pacientes que realizaram o TT, a prevalência de positividade foi de 21,6% entre os pacientes com CD4 ≥ 200 e de 9,49% entre os pacientes com CD4 < 200 (p=0,002). Permaneceram associados ao TT ≥ 5 mm, no extrato de contagem de CD4 ≥ 200: uso de HAART, uso de Crack e ter menos de 10 anos de escolaridade. Dos 811 pacientes que tinham indicação de repetir o teste, 314 (38,7%) repetiram o TT. A probabilidade de não repetir o TT foi de 42%. Permaneceram associadas a não repetição do teste: idade, IMC, sexo e escola. 201 pacientes foram acompanhados para o estudo da efetividade do tratamento da TBL. Desses, 126 (62,7%) iniciaram o tratamento para TBL, e 75 pacientes (37,3%) não iniciaram. A taxa de incidência de tuberculose na coorte de indicação para TBL foi de 11,25/1.000 pessoa-ano. Considerando apenas os 75 pacientes que não iniciaram ou abandonaram o tratamento para TBL, a taxa de incidência de tuberculose foi de 29,67/1.000 pessoa-ano. A estimativa da probabilidade de desenvolver a tuberculose entre os pacientes com indicação de tratamento da TBL no final do estudo foi de 1,9%. Entre os que não o realizaram ou a fizeram de maneira irregular, a estimativa da probabilidade de desenvolver a tuberculose foi de 5,2%. Os resultados encontrados demonstraram que não houve uma adequada adesão nem para a realização do primeiro teste tuberculínico nem para a repetição do mesmo. É imprescindível que sejam revistas as recomendações com relação ao início do tratamento da TBL estar baseado na realização do teste tuberculínico
Vidal, Júlia Souza. "Rifapentina no tratamento da infecção latente de tuberculose na população geral e em pessoas vivendo com HIV/AIDS : síntese das evidências." reponame:Repositório Institucional da UnB, 2014. http://repositorio.unb.br/handle/10482/16495.
Повний текст джерелаSubmitted by Ana Cristina Barbosa da Silva (annabds@hotmail.com) on 2014-10-14T18:50:40Z No. of bitstreams: 1 2014_JuliaSouzaVidal.pdf: 914586 bytes, checksum: cdd529fce2b521a476fb170770dbcc2e (MD5)
Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2014-10-15T15:02:02Z (GMT) No. of bitstreams: 1 2014_JuliaSouzaVidal.pdf: 914586 bytes, checksum: cdd529fce2b521a476fb170770dbcc2e (MD5)
Made available in DSpace on 2014-10-15T15:02:02Z (GMT). No. of bitstreams: 1 2014_JuliaSouzaVidal.pdf: 914586 bytes, checksum: cdd529fce2b521a476fb170770dbcc2e (MD5)
A infecção latente da tuberculose (ILTB) e a coinfecção com HIV são desafios para o controle da tuberculose. O objetivo do presente estudo foi avaliar e sintetizar as informações disponíveis na literatura sobre o tratamento da ILTB na população geral e em pessoas que vivem com HIV/AIDS para subsidiar a decisão do Programa Nacional de Controle da Tuberculose quanto à quimioprofilaxia secundária da ILTB. Foram pesquisadas as bases MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, EMBASE, LILACS, SCIELO, Tripdatabase, National Guideline Clearinghouse e Portal de Teses e Dissertações para identificar revisões sistemáticas, ensaios clínicos randomizados e diretrizes clínicas que avaliassem o tratamento da ILTB. A qualidade das evidências de ensaios clínicos randomizados foi avaliada por meio da escala de Jadad, e a qualidade das recomendações de outras fontes de evidências por meio da abordagem do GRADE – Grading of Recommendations Assessment, Development and Evaluation. As evidências disponíveis sugerem que não há diferença entre o tratamento de curta duração com rifapentina e a terapia preconizada, de 6 meses de isoniazida, na redução da incidência de tuberculose ativa ou mortalidade. A adesão foi melhor com a administração de rifapentina diretamente observada em comparação à isoniazida autoadministrada. A qualidade da evidência é moderada ou baixa. Rifapentina é recomendada por uma diretriz com base nessa qualidade da evidência. Os dados disponíveis são escassos e de qualidade moderada ou baixa, e os estudos em andamento também são abertos. As evidências disponíveis podem parecer insuficientes para apoiar a incorporação de rifapentina para ILTB na população geral e em pessoas que vivem com HIV/AIDS, mas aspectos como taxa de adesão, viabilidade da implementação, custos e peculiaridades locais devem ser considerados no momento da decisão. __________________________________________________________________________ ABSTRACT
Latent tuberculosis infection (LTBI) and HIV-coinfection are challenges to tuberculosis transmission control. We aimed to assess and synthesize the information available in the literature regarding the treatment LTBI in both general and HIV-positive population to support the Brazilian Tuberculosis Control Program decision-making for LTBI secondary chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, EMBASE, LILACS, SCIELO, Tripdatabase, National Guideline Clearinghouse and Brazilian Thesis Repository to identify systematic reviews, randomized clinical trials and clinical guidelines that assessed the LTBI pharmacological treatment. Quality of evidence from randomized clinical trials was assessed by using Jadad Scale and recommendations from other evidence sources by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The available evidences suggest that there are no differences between rifapentine short course treatment and the standard 6-month therapy with isoniazid in reducing active tuberculosis incidence or death. Adherence was better with directly observed therapy rifapentine compared to self-administered isoniazid. The quality of evidence is moderate or low. Rifapentine is recommended by one guideline based on this quality of evidence. Evidence available is scarce and of moderate or low quality, and ongoing trials are design as open label. Available evidences may seem insufficient to support rifapentine incorporation for LTBI in general and HIV-positive populations, but aspects such as adherence rates, implementation feasibility, costs and local particularities should be considered in the decision-making process.
Sears, Jacqueline L. "Machismo as a Determinant for HIV/STD Risk Behavior Among Latino MSM." Available to VCU users at:, 2006. http://hdl.handle.net/10156/1896.
Повний текст джерелаDoolabh, Deelan Sudhir. "The Influence of HIV-1 Subtype C LTR Genotype on Latency Potential." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29620.
Повний текст джерелаSheehan, Diana M. "Neighborhood-level Determinants of Delayed HIV Diagnosis and Survival among HIV-positive Latinos, Florida 2000-2011." FIU Digital Commons, 2016. http://digitalcommons.fiu.edu/etd/2502.
Повний текст джерелаNguyen, Kien. "EPIGENETIC REGULATION OF HIV-1 LATENCY BY HISTONE H3 METHYLTRANSFERASES AND H3K27 DEMETHYLASE." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1491495889537421.
Повний текст джерелаCarvalho, Carlos Gilvan Nunes de. "Fatores clínicos e epidemiológicos associados à sífilis, à toxoplasmose e à tuberculose latente em pacientes com HIV em um ambulatório especializado no Piauí." reponame:Repositório Institucional da FIOCRUZ, 2015. http://beta.arca.fiocruz.br/handle/icict/14502.
Повний текст джерелаMade available in DSpace on 2016-07-05T23:52:40Z (GMT). No. of bitstreams: 3 carlos_carvalho_ioc_mest_2015.pdf.txt: 201266 bytes, checksum: 6706ab9b44190a017bac229d11c39edd (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) carlos_carvalho_ioc_mest_2015.pdf: 1152131 bytes, checksum: 3accdbdc8e07500a4a30d624f15c68c4 (MD5) Previous issue date: 2015
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Teresina, PI, Brasil
INTRODUÇÃO: Apesar da redução da morbidade e mortalidade por doenças relacionadas à AIDS, alguns aspectos epidemiológicos das coinfecções com o vírus da imunodeficiência humana (HIV) ainda precisam sem melhor compreendidos. O HIV compartilha mecanismos de transmissão semelhantes aos da sífilis, doença bacteriana provocada pelo Treponema pallidum. O HIV pode contribuir com manifestações clínicas atípicas e apresentar dificuldades de respostas no tratamento da sífilis. As coinfecções com as formas latentes do bacilo Mycobacterium tuberculosis (ILTB) ou do parasito Toxoplasma gondii podem acarretar risco de desenvolvimento das doenças ativas sintomáticas, como a tuberculose e a neurotoxoplasmose, resultantes da imunossupressão pelo HIV. OBJETIVO: Este trabalho teve como objetivo avaliar as características clínico-epidemiológicas de um grupo de pacientes com HIV atendidos em um Serviço de Atenção Especializada (SAE) em Teresina, Piauí, e estimar a reatividade aos testes diagnósticos para agentes infecciosos da toxoplasmose, da sífilis e da ILTB, além de avaliar a associação desses fatores com essas coinfecções. MÉTODO: Foi realizado um estudo de série de casos, onde foram revisados os prontuários através de coleta de dados secundários, no período de junho a agosto de 2015. Foram incluídos no estudo 134 pacientes acompanhados entre os anos de 2009 e 2015. As variáveis independentes foram analisadas e tiveram suas médias, frequências e respectivas medidas de dispersão calculadas, considerando-se as reatividades aos testes diagnósticos como variáveis dependentes. A análise dos fatores associados foi realizada para cada coinfecção por modelos bivariados e de regressão multivariada RESULTADOS: Houve uma predominância de pacientes no sexo masculino (67,91%), com idades preferenciais no adulto jovem (65.67% de 30 a 59 anos), boa escolaridade e elevada média de contagem de LT-CD4 (565,58 células/mm3). A toxoplasmose manteve associação com significação estatística para indivíduos com 40 ou mais anos e com a ausência de dependência química, dislipidemia e tuberculose ativa. A sífilis manteve associação com presença de esteatose hepática, renda mensal de até 1 salário mínimo (SM) e entre homens que fazem sexo com homens (HSH). A ILTB, manteve-se associada a ausência de fossa séptica. CONCLUSÕES: A toxoplasmose, a sífilis e a ILTB são condições frequentes em pacientes com HIV em tratamento ambulatorial. Estas infecções estão associadas a fatores relacionados às suas vias de transmissão, o que aponta para a necessidade de adoção de medidas para sua prevenção neste grupo de pacientes
Despite the reduction in morbidity and mortality from AIDS-related illnesses, some epidemiological aspects of co-infections with the human immunodeficiency virus (HIV) still need without better understood. HIV share transmission mechanisms similar to those of syphilis, bacterial disease caused by Treponema pallidum. HIV can contribute to atypical clinical manifestations and present difficulties for answers in the treatment of syphilis. The co-infections with latent forms of the bacillus Mycobacterium tuberculosis (LTBI) or Toxoplasma gondii parasite can cause risk of developing symptomatic active disease, such as tuberculosis and toxoplasmosis immunosuppression resulting from HIV. OBJECTIVE: This study aimed to evaluate the clinical and epidemiological characteristics of a group of patients with HIV treated at a Specialized Care Service (SCE) in Teresina, Piauí, and estimate the reactivity to diagnostic tests for infectious agents of toxoplasmosis, syphilis and of LTBI, and to evaluate the association of these factors with these co-infections. METHOD: A study was conducted series of cases where records were reviewed by collecting secondary data, in the period from June to August 2015. The study included 134 patients followed between 2009 and 2015. The independent variables were analyzed and had their averages, frequencies and their calculated measures of dispersion, considering the reactivity to diagnostic tests as dependent variables. The analysis of associated factors was performed for each coinfection by bivariate and multivariate regression models RESULTS: There was a predominance of patients in males (67.91%), with preferential ages in young adults (65.67% 30-59 years), good education and high average LT-CD4 count (565.58 cells / mm3). Toxoplasmosis continued association with statistical significance for individuals with 40 or more years and the lack of addiction, dyslipidemia and active tuberculosis. Syphilis continued association with the presence of hepatic steatosis, monthly income of up 1 minimum wage (MW) and among men who have sex with men (MSM). The LTBI, remained associated with the absence of septic tank. CONCLUSIONS: toxoplasmosis, syphilis and LTBI are common conditions in HIV patients in outpatient treatment. These infections are associated with factors related to their transmission routes, which highlights the need to adopt measures for its prevention in this group of patients
Pearson, Richard. "Epigenetic Silencing of HIV Transcription Through Formation of Restrictive Chromatin Structures at the Viral LTR Drives the Progressive Entry of HIV into Latency." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1223040734.
Повний текст джерелаMates, Jessica Marie. "TRANSCRIPTIONAL REGULATION OF HIV-1." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1395845500.
Повний текст джерелаHuot, Nicolas. "Relation entre l’expression des LAT et du gène RL2 pendant la latence du virus HSV-1." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA114860/document.
Повний текст джерелаThe herpes simplex virus type 1 (HSV-1) establishes a latent infection in the nervous system of humans, in which latency associated transcripts (LATs) accumulate in infected neurons. The key role of LATs in the control of viral latency is well established. However, since their discovery in the 80s, their mechanism of action remains unclear.The LAT gene is transcribed into a 8.3 kb primary LAT that is rapidly spliced, leading to the formation of two stable LATs; LAT2kb and LAT1.5kb. Remarkably, the LAT2kb and LAT1.5kb are introns. Their stability is the result of a non-canonical sequence of the branching point, which results in maintaining the lariat structure.Moreover, the region of the genome encoding the LATs also contains the RL2 gene, encoding ICP0 that acts upstream in the cascade of viral reactivation. Previous studies have shown that RL2 unspliced transcripts may accumulate in the main site of HSV-1 latency (trigeminal ganglia). We have characterized these unspliced transcripts RL2 gene in latently infected tissues. They reproducibly contain intron 1 and are particularly abundant in latently infected tissues where LATs also accumulate. We distinguished several types of latently infected tissues, the two most representative examples being the trigeminal ganglion (strong expression of LATs and accumulation of non-spliced transcripts RL2) and, in the opposite, the superior cervical ganglion (no accumulation of LAT compared with the amounts expressed during the acute phase of infection, and little expression in non-spliced RL2 transcripts). In all cases, the reality of the latent nature of the infection was confirmed by the presence of viral genome with no expression of mature transcripts from early viral gene (represented by the thymidine kinase gene) or late (UL18 gene).These results suggest a relationship between the presence of LAT and the accumulation of non-spliced RL2 transcripts, which could be related to the maintenance of latent infection in these tissues
Elbezanti, Weam Othman. "The Effect of Mutating RUNX1 Binding Site on HIV-1 Replication and Novel HIV-1 Latency Reversal through Using Clinically Prescribed Benzodiazepines." Thesis, University of the Sciences in Philadelphia, 2019. http://pqdtopen.proquest.com/#viewpdf?dispub=13862426.
Повний текст джерелаThe major barrier to curing HIV-1 infection is latency. HIV-1 latent cells are those in which the viral genome has been integrated into the host cell genome but the virus does not produce the primary infectious agents, viral RNA and proteins. Latency can occur when the virus directly infects long-lived memory CD4+ T cells or infects active CD4+ T cells that have the potential to become memory T cells. The virus persists inside those cells as long as they are alive. This dormancy provides a reservoir of HIV-1 virus in memory T cells, which can cause infection relapse whenever antiretroviral therapy (ART) is discontinued. The situation is further complicated by the fact that multiple reservoirs of HIV-1 virus can be established at early stages of infection.
The major reservoir lies in the CD4+ T cells present in blood, lymph nodes and the spleen. Unfortunately, ART fails to target hidden HIV-1 virus that persists in resting T-cells. Furthermore, life-long ART use increases the chances that mutant virus will develop which will be resistant to continued therapy. Therefore, various studies have explored mechanisms to eradicate the latent HIV-1 reservoir. One proposed strategy to target this reservoir is known as “shock and kill”. The proposed shock and kill strategy initially “shocks” the HIV-1 virus out of latency with latency reversing agents (LRAs). The reactivated virus can then be controlled by ART and cytotoxic CD8+ T cells (CTLs), which kill the infected cells. Despite the great findings regarding reactivating HIV-1 latency in vitro and ex vivo, tested LRAs proved unsuccessful in reactivating HIV-1 virus in clinical trials.
Different factors can contribute to establishment of HIV-1 latency and different reservoirs in different immune cells and tissues are established early after HIV-1 infection. Therefore, synergy between multiple LRAs should be sought and studied for successful reactivation of the latent viral pool.
Runt Related Transcription Factor 1 (RUNX1) is a key transcription factor that is important during T cell development and has been shown to recruit different transcription factors in a context dependent manner. It has been shown to be involved in repressing various genes and it also interacts with chromatin modifiers that can alter the landscape of the chromatin and modify its compaction. Our lab has shown that there is a putative RUNX1 binding site on HIV-1 long terminal repeats (LTR) and the transfection of RUNX1 can suppress HIV-1 transcription. In addition, our lab has shown that the benzodiazepine, RO5-3335, which pharmacologically inhibits RUNX1, synergizes with vorinostat (SAHA), an HDAC inhibitor to reactivate latent HIV-1.
Using DNA cloning, an HIV-1 virus with a mutated RUNX1 binding site was constructed. Then, replication, infectivity and fitness of the mutated virus were examined and compared to a control virus using ELISA, RT, PCR, and TA cloning techniques. We have found that this mutated virus replicates faster and has more fitness and infectivity than the control virus with an intact RUNX1 binding site. Our results show that inhibition of RUNX1 binding to HIV-1 3’ long terminal repeat (LTR) positively affects viral replication and infectivity. This suggests that RUNX1 host transcription factor suppresses HIV-1 replication through its transcriptional repressor function and it possibly contributes to establishment of latency.
We screened clinically prescribed benzodiazepines (BDZs) to identify reactivators for latent HIV-1 virus. Using flow cytometry, we have found most of these BDZs synergized with SAHA in reactivation of latent HIV-1. Unlike the other BDZs tested, alprazolam was able to reactivate HIV-1 even when not in combination with SAHA. The effect of alprazolam on RUNX1 responsive genes was further investigated using qPCR. Alprazolam was found to affect RUNX1 responsive genes similarly to RO5-3335, a known RUNX1 inhibitor. The effect of alprazolam on IFNγ and TNFα that are produced from cytotoxic T cells (CTLs) was also examined. Alprazolam enhanced CTL function that was shown in the literature to be attenuated by SAHA. Thus, alprazolam successfully reverses HIV-1 latency and decreases the side effects of SAHA on CTL function when used in combination.
Paganella, Machline Paim. "Associação da incidência de dislipidemia e anormalidades de glicose com o tratamento antirretroviral em uma coorte de crianças infectadas pelo HIV na américa latina (NISDI/PLACES)." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/104126.
Повний текст джерелаKussen, Gislene Maria Botão. "Análise do ensaio imunológico igra versus prova tuberculínica para detecção de infecçção latente por Mycobacterium tuberculosis em pacientes HIV positivos." reponame:Repositório Institucional da UFPR, 2014. http://hdl.handle.net/1884/36972.
Повний текст джерелаCo-orientadora: Profª. Drª. Libera Maria Dalla Costa
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa : Curitiba, 31/10/2014
Inclui referências
Resumo: Indivíduos infectados com M. tuberculosis (MTB) sem doença ativa têm infecção latente por tuberculose (ILTB). Pacientes portadores de HIV, por serem imunodeprimidos, são mais propensos a desenvolver TB ativa. A identificação da ILTB permite a intervenção precoce com o uso de quimioprofilaxia e, consequentemente, contribui para uma menor morbidade e mortalidade neste grupo de pacientes. A prova tuberculínica (PT) mantém-se como o método padrão-ouro para diagnóstico de ILTB, apesar de apresentar limitações técnicas. O objetivo deste estudo foi avaliar o desempenho do teste imunológico QuantiFERON TB Gold In Tube®, que se baseia na avaliação da resposta do gama interferon para antígenos específicos de MTB, para diagnóstico de ILTB em pacientes com HIV residentes em um país com alta incidência de tuberculose, comparando estes achados com os resultados da PT. Realizou-se um estudo de Coorte, que incluiu 140 pacientes, que foram acompanhados por um período médio de 12 meses (6 a 21 meses). Um total de 115 (82%) e nove (6,4%) pacientes apresentou ambos os testes negativos e positivos, respectivamente. Entre os resultados discordantes observou-se em 12 (8,6%) pacientes IGRA positivo com PT negativa e em quatro (3%) pacientes resultados de IGRA negativo com PT positiva. O coeficiente de Cohen Kappa foi de 0,214, mostrando uma concordância pobre entre as duas técnicas. Comparando os resultados obtidos em ambos os testes, pode-se verificar que não houve evidência estatística de que um ou outro método seja superior (p = 0,08). Não foi observada nenhuma correlação entre os resultados de IGRA e PT e os valores de LT CD4+, embora em pacientes com maior imunossupressão (LT CD4+ <300 células/mm3) observamos testes IGRA positivos e PT não reatoras. No período de acompanhamento, um paciente que apresentava PT e IGRA negativos evoluiu para morte por septicemia, e outro com resultados discordantes (IGRA+/PT-) apresentou conversão da PT. Avaliando as características de desempenho do IGRA, considerando PT como o teste padrão-ouro, a sensibilidade observada foi em torno de 70%, com especificidade de 90%. Considerando os resultados de ambos os testes como verdadeiro positivo, um aumento de 8% na positividade pode ser observado. O tratamento da ILTB neste grupo de pacientes poderá ter impacto sobre a taxa de tuberculose ativa e sobrevivência de portadores do HIV, porém isso ainda precisa ser avaliado ao longo dos anos. Palavras-chave: HIV, Mycobacterium tuberculosis, teste tuberculínico
Abstract: Individual infected with M. tuberculosis (MTB) without active disease can present latent tuberculosis infection (LTBI). These patients in the context of impaired immune systems, such as HIV+, are more likely to progress to active TB. Identification of LTBI allows early intervention with the use of chemoprophylaxis, consequently contributing to a lower morbidity and mortality in this group of patients. Tuberculin skin test (TST) has remained as gold standard method to diagnosis LTBI, despite it presents technical limitations. The aim of this study was to assess the performance of the new immunological test Quantiferon TB Gold in tube, which is based on evaluating the IFN-gamma response to specific MTB antigens, to LTBI diagnosis on HIV patients from a country with high-tuberculosis burden, comparing the findings with TST results. It was a cohort study that included 140 patients, who are followed up for 21 months. A total of 115 (82%) and 9 (6.4%) patients had both tests negative and positive, respectively. Disagreement results occurred in 12 (8.6%) patients, whom had IGRA positive with negative TST and 4 (3%) patients that showed positive TST with negative IGRA. The Cohen Kappa coefficient found was 0.214, showing a poor concordance between both techniques. Comparing the results obtained by both tests, there was no statistical evidence that either method is different, because of the discrepancies occurred in a statistically identical manner (p = 0,08). None correlation between the results and CD4+ LT values was observed, though in patients with lowers CD4+ LT values (<300 cell/mm3) only IGRA tests were positive. In the period of follow up one patient, that presented both negative tests, evolved to death from sepsis, and another with discordant results (IGRA+/TST-) presented TST conversion. Evaluating the operational characteristics of IGRA, considering TST as the gold standard test, the sensitivity observed was around 70% and the specificity 90%. Considering the results of both tests as true positive an incremental of 8% in the positivity could be observed. If the LTBI treatment in this group of patients will have some impact on the rate of active tuberculosis and survival of HIV carriers still need to be evaluated over the years. Keywords: HIV, Mycobacterium tuberculosis, tuberculin skin test.
García, Vidal Edurne. "Identification and characterization of novel latency-reversing agents to clear HIV-1 viral reservoir." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669732.
Повний текст джерелаCurrent antiretroviral therapy has changed the perspective of HIV-1 infection from a lethal illness to a chronic disease. However, the HIV-1 latent reservoir is a major hurdle to achieve a cure for HIV-1. The “shock and kill” strategy is based on inducing viral transcription of latent HIV-1 provirus followed by the selective killing of reactivated cells. Although several latency-reversing agents (LRAs) have been identified and tested, none of them has been able to efficiently eradicate the HIV-1 latent reservoir. Based on the need of novel agents and strategies to efficiently clear the latent reservoir, we evaluated compounds developed as modulators of the innate immune response or designed to modulate the cell cycle progression as novel agents able to purge the viral reservoir. The study of innate immune modulators as agents able to clear the HIV-1 reservoir might represent an alternative due to its intrinsic functions, i. e., protection and clearance of infections. The innate immune regulator acitretin, an FDA-approved compound for psoriasis, has been proposed to induce HIV-1 reactivation and selective killing of the infected cells. However, the effect of acitretin on HIV-1 reactivation was negligible in the vast majority of models tested, albeit activation of RIG-I pathway was detected and a mild induction of viral reactivation was observed in a non-clonal T cell model. Moreover, acitretin treatment did not induce the selective killing of the infected cells. Anti-cancer compounds have also been proposed as candidate therapies targeting the latent reservoir, mainly due to the ability of certain agents to modify gene transcription or to promote cell apoptosis. The assessment of the HIV-1 reactivation potential of an anti-cancer compound library reported several molecular targets whose inhibition promoted HIV-1 latency reversal, including the histone deacetylases (HDAC), Janus kinases (JAK), IκB kinases (IKKs) and heat shock proteins (HSPs). Among the new identified LRAs, Aurora kinases inhibitors (AURKi) represented the largest family of compounds not previously described as LRA that significantly and consistently showed HIV-1 reactivation capacity. AURKi were able to enhance the HDACi-mediated reactivation, suggesting that AURKi are able to target a distinct set of integrated provirus than that reactivated by the well-described HDAC inhibitors. Interestingly, AURKi restricted acute HIV-1 infection, suggesting a dual role for these compounds on HIV-1 infection. Midostaurin, a multi-kinase inhibitor approved for leukemia treatment, was also identified as an LRA. Midostaurin induced HIV-1 latency reactivation, either alone or in combination with other LRAs, consistent with previous reports that associated this activity with the activation of the innate immune NF-κB pathway. Moreover, we also observed a non-yet-reported and SAMHD1-dependent inhibitory effect of HIV-1 replication in primary cells. The enhanced capacity to promote HIV-1 reactivation of AURKi and midostaurin in combination with other LRAs supports the idea that different agents are needed to reactivate all latent provirus, presenting different specificities towards HIV-1 provirus reactivation depending on its integration site in the host genome. Furthermore, these observations also raise concerns on the models used to study HIV-1 latency, as clonal models might not be suitable due to the lack of heterogeneity in proviral insertion site, characteristic of non-clonal models. Altogether, our results suggest that modulation of innate immunity and cell cycle may be taken into account for the design of future LRAs for the “shock and kill” strategy; however, further research is still necessary before it can lead to an HIV-1 cure.
Wang, Ling, Guang Y. Li, Jonathan P. Moorman, and Shunbin Ning. "MicroRNA Regulation Of Viral Immunity, Latency, And Carcinogenesis of Selected Tumor Viruses and HIV." Digital Commons @ East Tennessee State University, 2015. https://doi.org/10.1002/rmv.1850.
Повний текст джерела