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1.
MMWR Morb Mortal Wkly Rep ; 69(2): 35-39, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31945033

RESUMO

Transgender women* in the United States are disproportionately affected by human immunodeficiency virus (HIV) infection because of multiple factors, including stigma related to gender identity, unstable housing, limited employment options, and high-risk behaviors, such as sex work, unprotected receptive anal intercourse, and injection drug use, that tend to increase their vulnerability to becoming infected with HIV (1,2). In a recent meta-analysis of 88 U.S. studies conducted during 2006-2017, the mean estimated laboratory-confirmed prevalence of HIV infection among transgender women was 14.2%, and the mean self-reported prevalence estimate was 21.0% (3). The Ending the HIV Epidemic initiative calls for accelerating the implementation of evidence-based strategies in the right geographic areas targeted to the right persons to end the HIV epidemic in the United States (4). HIV partner services are effective strategies offered by public health workers to persons with a diagnosis of HIV infection (index persons) and their sex or needle-sharing partners (partners), who are notified of potential HIV exposure and offered HIV testing and related services. CDC analyzed HIV partner services data submitted by 61 health departments† during 2013-2017. Among 208,304 index persons, 1,727 (0.8%) were transgender women. Overall, 71.5% of index transgender women were interviewed for partner services, which was lower than that for all index persons combined (81.1%). Among 1,089 transgender women named as partners by index persons, 71.2% were notified of potential HIV exposure, which was lower than that for all partners combined (77.1%). Fewer than half (46.5%) of notified transgender women partners were tested for HIV, and approximately one in five (18.6%) of those who were tested received a new diagnosis of HIV infection, slightly higher than for all partners combined (17.6%). Additional efforts are needed to effectively implement partner services among transgender women and identify those whose infection with HIV is undiagnosed, provide timely prevention and care services, reduce HIV transmission, and contribute to ending the HIV epidemic.


Assuntos
Assistência à Saúde , Infecções por HIV/terapia , Parceiros Sexuais , Pessoas Transgênero , Adolescente , Adulto , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estados Unidos/epidemiologia , Adulto Jovem
2.
MMWR Morb Mortal Wkly Rep ; 69(4): 97-102, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31999684

RESUMO

Identifying persons with human immunodeficiency virus (HIV) infection who are unaware of their status and linking them to care are critical steps in achieving viral suppression and reducing the risk for transmitting HIV (1). In 2017, 43% of new diagnoses of HIV infection were among persons who self-identify as blacks or African Americans (blacks) (2), who represent 13% of the U.S. population (3). Fewer blacks, compared with whites, were linked to HIV medical care within 90 days of diagnosis, retained in care, or virally suppressed (4). Ending the HIV Epidemic (EHE) is an initiative intended to reduce new HIV infections by 90% from 2020 to 2030 (5). EHE's Phase 1 is focused on 50 jurisdictions* that accounted for >50% of new diagnoses during 2016-2017 and seven states† with disproportionate HIV prevalence in rural areas (5). The purpose of this analysis was to examine HIV testing outcomes among blacks in high prevalence EHE jurisdictions, using CDC's 2017 National HIV Prevention Program Monitoring and Evaluation data. Blacks accounted for 43.2% of CDC-funded tests and 49.1% of new diagnoses of HIV infection. Seventy-nine percent of blacks with newly diagnosed HIV infection were linked to HIV medical care within 90 days (below the 2010 National HIV/AIDS Strategy goal of 85%), 71.4% interviewed for partner services, and 81.8% referred to prevention services. To achieve the goals of EHE, HIV prevention programs should focus on locally tailored evidence-based§ testing strategies to enhance and overcome barriers for linkage to and retention in care and reduce onward HIV transmission and HIV-related disparities.


Assuntos
Afro-Americanos/estatística & dados numéricos , Infecções por HIV/etnologia , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Saúde da População Rural/etnologia , Saúde da População Rural/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto Jovem
3.
Med Klin Intensivmed Notfmed ; 115(1): 67-78, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31950206

RESUMO

Injuries of healthcare workers with sharp instruments are considered among the most frequent occupational accidents in hospitals. In at least half of the cases, the instruments are contaminated with blood and therefore bear an infection risk with bloodborne pathogens, such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Needlestick injuries require besides immediate medical intervention, such as rinsing and disinfection of the wound or skin contamination, a prompt clarification of the immune status and if necessary a postexposure prophylaxis. Furthermore, follow-up examinations are required for up to 6 months after the accident. Information about the infectious state of the index person considerably facilitates the procedure. All healthcare workers should know the management of needlestick injuries. Preventive measures refer to the reduction of the number of needlestick injuries by improving work organization and usage of needle devices with safety features as well as to the reduction of infection risk by hepatitis B vaccination and wearing safety gloves.


Assuntos
Pessoal de Saúde , Ferimentos Penetrantes Produzidos por Agulha , Exposição Ocupacional , Acidentes de Trabalho , Infecções por HIV/prevenção & controle , Infecções por HIV/terapia , Hepatite B/prevenção & controle , Hepatite B/transmissão , Hepatite C/prevenção & controle , Hepatite C/transmissão , Humanos
4.
BMC Public Health ; 19(1): 1509, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718603

RESUMO

BACKGROUND: Health resources are limited, which means spending should be focused on the people, places and programs that matter most. Choosing the mix of programs to maximize a health outcome is termed allocative efficiency. Here, we extend the methodology of allocative efficiency to answer the question of how resources should be distributed among different geographic regions. METHODS: We describe a novel geographical optimization algorithm, which has been implemented as an extension to the Optima HIV model. This algorithm identifies an optimal funding of services and programs across regions, such as multiple countries or multiple districts within a country. The algorithm consists of three steps: (1) calibrating the model to each region, (2) determining the optimal allocation for each region across a range of different budget levels, and (3) finding the budget level in each region that minimizes the outcome (such as reducing new HIV infections and/or HIV-related deaths), subject to the constraint of fixed total budget across all regions. As a case study, we applied this method to determine an illustrative allocation of HIV program funding across three representative oblasts (regions) in Ukraine (Mykolayiv, Poltava, and Zhytomyr) to minimize the number of new HIV infections. RESULTS: Geographical optimization was found to identify solutions with better outcomes than would be possible by considering region-specific allocations alone. In the case of Ukraine, prior to optimization (i.e. with status quo spending), a total of 244,000 HIV-related disability-adjusted life years (DALYs) were estimated to occur from 2016 to 2030 across the three oblasts. With optimization within (but not between) oblasts, this was estimated to be reduced to 181,000. With geographical optimization (i.e., allowing reallocation of funds between oblasts), this was estimated to be further reduced to 173,000. CONCLUSIONS: With the increasing availability of region- and even facility-level data, geographical optimization is likely to play an increasingly important role in health economic decision making. Although the largest gains are typically due to reallocating resources to the most effective interventions, especially treatment, further gains can be achieved by optimally reallocating resources between regions. Finally, the methods described here are not restricted to geographical optimization, and can be applied to other problems where competing resources need to be allocated with constraints, such as between diseases.


Assuntos
Algoritmos , Assistência à Saúde/economia , Organização do Financiamento/métodos , Infecções por HIV/economia , Custos de Cuidados de Saúde , Recursos em Saúde , Alocação de Recursos , Tomada de Decisões , Infecções por HIV/terapia , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Análise Espacial , Ucrânia
5.
BMC Health Serv Res ; 19(1): 761, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660976

RESUMO

BACKGROUND: Accessing HIV-related care is challenging for formerly incarcerated people with HIV. Interventions informed by the perspectives of these individuals could facilitate engagement with care and address competing priorities that may act as barriers to this process. METHODS: We used concept mapping to identify and prioritize the main obstacles to engaging with HIV-related care following prison release. In brainstorming sessions, formerly incarcerated people with HIV generated responses to a focused prompt regarding the main barriers to reengaging with care. These were consolidated in 35 statements. Next, participants sorted the consolidated list of responses into groups and rated each from lowest to highest in terms of its importance and feasibility of being addressed. We used cluster analysis to generate concept maps that were interpreted with participants. RESULTS: Overall, 39 participants participated in brainstorming sessions, among whom 18 returned for rating and sorting. Following analysis, a seven-cluster map was generated, with participants rating the 'Practical Considerations' (e.g. lack of transportation from prison) and 'Survival Needs' (e.g. securing housing and food) clusters as most important. Although ratings were generally similar between women and men, women assigned greater importance to barriers related to reconnecting with children. CONCLUSIONS: Using concept mapping, we worked with formerly incarcerated people with HIV to identify and prioritize key challenges related to accessing health and social services following prison release. Transitional intervention programs should include programs and processes that address meeting basic subsistence needs and overcoming logistical barriers related to community re-entry.


Assuntos
Formação de Conceito , Infecções por HIV/terapia , Prisioneiros/estatística & dados numéricos , Cuidado Transicional/organização & administração , Adulto , Análise por Conglomerados , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ontário
6.
BMC Infect Dis ; 19(1): 906, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664925

RESUMO

BACKGROUND: Migrants often face barriers to accessing healthcare. We examined disparities in access to and use of HIV-related health services between migrant and non-migrant people recently diagnosed with HIV living in the Netherlands, taken into account sexual orientation. Also, we examined differences in experiences in living with HIV between these groups. METHODS: We used a questionnaire and clinical data collected between July 2013 and June 2015 among migrant and non-migrant participants of the European cross-sectional aMASE (Advancing Migrant Access to health Services in Europe) study in the Netherlands. Using univariable logistic regression analyses, we compared outcomes on between migrants and non-migrants, stratified by sexual orientation (with non-migrant men having sex with men [MSM] as the reference group). RESULTS: We included 77 migrant MSM, 115 non-migrant MSM, 21 migrant heterosexual men, 14 non-migrant heterosexual men and 20 migrant women. In univariable analyses, all heterosexual groups were less likely to ever have had an HIV-negative test before their diagnosis and were more likely to be diagnosed late than non-migrant MSM. All migrant groups were more likely to have experienced difficulties accessing general healthcare in the Netherlands and were less likely to have heard of post-exposure prophylaxis than non-migrant MSM. Migrants frequently reported uncertainty about their rights to healthcare and language barriers. Most (93%) participants visited a healthcare facility in the 2 years before HIV diagnosis but only in 41% an HIV test was discussed during that visit (no statistical difference between groups). Migrant heterosexuals were more likely to have missed appointments at their HIV clinic due to the travel costs than non-migrant MSM. Migrant MSM and women were more likely to have experienced HIV discrimination in the Netherlands than non-migrant MSM. CONCLUSION: Disparities in access to and use of HIV-related health services and experiences exist by migrant status but also by sexual orientation. Our data suggests heterosexual men and women may particularly benefit from improved access to HIV testing (e.g., through provider-initiated testing), while migrant MSM may benefit from improved access to HIV prevention interventions (e.g., pre-exposure prophylaxis).


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Acesso aos Serviços de Saúde , Disparidades em Assistência à Saúde , Comportamento Sexual , Migrantes , Adulto , Estudos Transversais , Feminino , Infecções por HIV/prevenção & controle , Heterossexualidade , Homossexualidade Masculina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Países Baixos , Minorias Sexuais e de Gênero , Inquéritos e Questionários , Viagem/economia
7.
BMC Public Health ; 19(1): 1409, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664967

RESUMO

BACKGROUND: People living with HIV (PLWH) have a high level of interest in quitting smoking, but only a small proportion have sustainable abstinence 6 months after cessation. Few investigations have focused on relapse to smoking among PLWH. In this investigation, we evaluated the prevalence of relapse after smoking cessation and the characteristics associated with smoking relapse using a retrospective, longitudinal cohort of PLWH during an eight-year observation. METHODS: All patients aged ≥19 years that reported current smoking during the study period and then reported not smoking on a subsequent tobacco use questionnaire (quitters) were eligible for the study. In addition, patients required at least one subsequent follow-up visit after quitting where smoking status was again reported to allow for assessment of relapse. A Cox proportional hazard model was fit to evaluate factors associated with smoking relapse in PLWH attending routine clinical care. RESULTS: Of the 473 patients who quit smoking in the study, 51% relapsed. In multivariable analysis, factors significantly associated with a higher likelihood of relapse were anxiety symptoms (HR = 1.55, 95% CI [1.11, 2.17]) and at-risk alcohol use (HR = 1.74, 95% CI [1.06, 2.85]), whereas antiretroviral therapy (ART) adherence (HR = 0.65, 95% CI [0.49, 0.99]) and longer time in care (HR = 0.94, 95% CI [0.91, 0.98]) were associated with a reduced likelihood of relapse after cessation. CONCLUSION: Our study underscores the high prevalence of smoking relapse that exists among PLWH after they quit smoking. Successful engagement in mental health care may enhance efforts to reduce relapse in the underserved populations of PLWH.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Infecções por HIV/epidemiologia , Transtornos Mentais/epidemiologia , Fumar/epidemiologia , Fumar/psicologia , Adulto , Alabama/epidemiologia , Feminino , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Estudos Retrospectivos , Fatores de Risco , Abandono do Hábito de Fumar/psicologia , Abandono do Hábito de Fumar/estatística & dados numéricos
8.
Rev Bras Epidemiol ; 22Suppl 1(Suppl 1): e190010, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576986

RESUMO

INTRODUCTION: Care continuum models have supported recent strategies against sexually transmitted diseases, such as HIV and Hepatitis C (HCV). METHODS: HIV, HCV, and congenital syphilis care continuum models were developed, including all stages of care, from promotion/prevention to clinical control/cure. The models supported the intervention QualiRede, developed by a University-Brazilian National Health System (SUS) partnership focused on managers and other professionals from six priority health regions in São Paulo and Santa Catarina. Indicators were selected for each stage of the care continuum from the SUS information systems and from the Qualiaids and QualiAB facility's process evaluation questionnaires. The indicators acted as the technical basis of two workshops with professionals and managers in each region: the first one to identify problems and to create a Regional Technical Group; and the second one to design action plans for improving regional performance. RESULTS: The indicators are available at www.qualirede.org. The workshops took place in the regions of Alto Tietê, Baixada Santista, Grande ABC, and Registro (São Paulo) and of Foz do Rio Itajaí (Santa Catarina), which resulted in regional action plans in São Paulo, but not in Santa Catarina. A lack of awareness was observed regarding the new HIV and HCV protocols, as well as an incipient use of indicators in routine practices. CONCLUSION: Improving the performance of the care continuum requires appropriation of performance indicators and coordination of care flows at local, regional, and state levels of management.


Assuntos
Continuidade da Assistência ao Paciente/estatística & dados numéricos , Infecções por HIV/terapia , Pesquisa sobre Serviços de Saúde/estatística & dados numéricos , Hepatite C/terapia , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Sífilis Congênita/terapia , Brasil , Infecções por HIV/epidemiologia , Promoção da Saúde/métodos , Promoção da Saúde/estatística & dados numéricos , Hepatite C/epidemiologia , Humanos , Programas Nacionais de Saúde , Inquéritos e Questionários , Sífilis Congênita/epidemiologia
9.
N Engl J Med ; 381(13): 1240-1247, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31509667

RESUMO

The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.).


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Infecções por HIV/terapia , HIV-1 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Receptores CCR5/genética , Adulto , Antirretrovirais/uso terapêutico , Contagem de Células Sanguíneas , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Carga Viral
10.
Science ; 365(6457): 1025-1029, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488688

RESUMO

Treatment of SIV-infected rhesus macaques with short-term antiretroviral therapy (ART) and partially overlapping infusions of antibody to integrin α4ß7 was reported to induce durable posttreatment viral suppression. In an attempt to replicate those observations, we treated macaques infected with the same virus and with the same ART and monoclonal antibody (mAb) regimens (anti-α4ß7 versus control mAb). Sequencing demonstrated that the virus used was actually SIVmac239-nef-stop, not wild-type SIVmac239. A positive correlation was found at 2 weeks after infection between the frequency of repair of attenuated Nef-STOP virus to pathogenic Nef-OPEN and plasma SIV RNA levels. Levels of plasma viremia before the first antibody infusion and preinfection levels of α4ß7 hi CD4+ T cells, but not treatment with antibody to α4ß7 , correlated with levels of viral replication upon discontinuation of all treatments. Follow-up plasma viremia, peripheral blood CD4+ T cell counts, and lymph node and rectal tissue viral load were not significantly different between anti-α4ß7 and control mAb groups.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Infecções por HIV/terapia , Integrina alfa4/imunologia , Cadeias beta de Integrinas/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Animais , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Códon de Terminação , Linfonodos/virologia , Macaca mulatta , RNA Viral/sangue , Reto/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/imunologia , Viremia/sangue , Viremia/imunologia , Viremia/terapia , Viremia/virologia , Replicação Viral
11.
Science ; 365(6457): 1029-1033, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488689

RESUMO

Sustained virologic control of human immunodeficiency virus type 1 (HIV-1) infection after discontinuation of antiretroviral therapy (ART) is a major goal of the HIV-1 cure field. A recent study reported that administration of an antibody against α4ß7 induced durable virologic control after ART discontinuation in 100% of rhesus macaques infected with an attenuated strain of simian immunodeficiency virus (SIV) containing a stop codon in nef We performed similar studies in 50 rhesus macaques infected with wild-type, pathogenic SIVmac251. In animals that initiated ART during either acute or chronic infection, anti-α4ß7 antibody infusion had no detectable effect on the viral reservoir or viral rebound after ART discontinuation. These data demonstrate that anti-α4ß7 antibody administration did not provide therapeutic efficacy in the model of pathogenic SIVmac251 infection of rhesus macaques.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Integrina alfa4/imunologia , Cadeias beta de Integrinas/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Animais , Antirretrovirais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Códon de Terminação , DNA Viral/sangue , Infecções por HIV/terapia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/imunologia
12.
Science ; 365(6457): 1033-1036, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488690

RESUMO

A study in nonhuman primates reported that infusions of an antibody against α4ß7 integrin, in combination with antiretroviral therapy, showed consistent, durable control of simian immunodeficiency virus (SIV) in rhesus macaques. The antibody used has pleiotropic effects, so we set out to gain insight into the underlying mechanism by comparing this treatment to treatment with non-neutralizing monoclonal antibodies against the SIV envelope glycoprotein that only block α4ß7 binding to SIV Env but have no other host-directed effects. Similar to the initial study, we used an attenuated strain of SIV containing a stop codon in nef. The study used 30 macaques that all began antiretroviral therapy and then were divided into five groups to receive different antibody treatments. Unlike the published report, we found no sustained virologic control by these treatments in vivo.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Integrina alfa4/imunologia , Cadeias beta de Integrinas/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , DNA Viral/sangue , Produtos do Gene env/imunologia , Infecções por HIV/terapia , Macaca mulatta , RNA Viral/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T/imunologia , Carga Viral , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/imunologia , Replicação Viral
13.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414741

RESUMO

BACKGROUND: Inhibition of viral genes through siRNA seems to be promising for treatment of complicated viral infections like human immunodeficiency virus (HIV-1). HIV-1 Tat (Trans Activator of Transcription) and Nef (Negative regulatory Factor) proteins are very interesting targets for designing siRNAs. METHODS: The effectiveness of suppressing Tat and Nef was investigated using three specific siTATs and three siNEFs. They were used to transfect the developed stable and infected Human Embryonic Kidney cells (HEK293) as an ex-vivo model. Both stable and virus infected HEK293 cells were transfected with each siTAT and siNEF. The inhibitory effect was evaluated using qRT-PCR, western blot analysis, and HIV P24 ELISA. RESULTS: siTAT-100, siTAT-162, and siNEF-136 and at a concentration of 100 nM/mL showed the most inhibitory effect on their target genes. CONCLUSIONS: Utilization of more developed molecular inhibition strategies such as RNAi or even a combination of different molecular approaches could be promising to overcome emerging HIV escape mutants.


Assuntos
Regulação Viral da Expressão Gênica , HIV-1/genética , Interferência de RNA , Replicação Viral/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Células HEK293 , Infecções por HIV/terapia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , RNA Interferente Pequeno/genética , Terapêutica com RNAi/métodos
15.
Psychiatriki ; 30(2): 120-128, 2019.
Artigo em Grego Moderno | MEDLINE | ID: mdl-31425140

RESUMO

Despite the large progress during the last decades in the medical treatment of HIV/AIDS infection, people living with HIV nevertheless face multiple adversities at various levels of their lives. Mental disorders, in particular, are the most common comorbidities in HIV infection with negative consequences in adherence to antiretroviral medication, disease progress and overall quality of life. HIVrelated stigma, still quite intense in Greece, is one of the most debilitating factors concerning people's living with HIV mental health. The present study looked at the clinical presentation at intake and treatment requests of 191 (83% males) people living with HIV who addressed the psychological support service of the non-governmental organization 'Centre for Life' during the years 2016- 18. Data were collected through a semi-structured clinical interview and administration of adapted questionnaires (PHQ-9, BAI, CAGE), which resulted in 7 dichotomous variables related to clinical presentation and 13 dichotomous variables related to treatment requests at intake. To analyze data, we constructed frequency tables and performed chi-square tests. In the whole sample, 42.2% presented anxiety disorders, 40.3% depression, 28.8% occasional substance use, 17.5% problematic use of alcohol and 13.6% intravenous drug use. Moreover, 14% reported at least one suicide attempt in the past and 9.2% current suicidal ideation. Apart from more frequent intravenous drug use among heterosexual males and more frequent occasional/recreational drug use among men who have sex with men, no other differences related to gender, age group, sexual orientation or ethnicity were observed in the initial clinical presentation. Similarly, the most frequent treatment requests were homogenously distributed in our sample, such as depressive symptoms (58.6%), difficulties in romantic relationships (48.7%), accepting being HIV positive (42.9%), anxiety symptoms (42.4%) and issues of negative self-esteem (40.8%). The presence of clinically significant depression was found to be related to a wider range of treatment requests compared to other mental health problems. A large group of requests focused on interpersonal relationships difficulties (e.g. disclosure anxiety, social isolation, disturbed relationships with familiar persons). This indicates an important area of psychological intervention. HIV infection may affect many levels of an individual's life, including their mental health. Respectively, HIV treatment needs to adopt a more holistic approach.


Assuntos
Síndrome de Imunodeficiência Adquirida/psicologia , Síndrome de Imunodeficiência Adquirida/terapia , Infecções por HIV/psicologia , Infecções por HIV/terapia , Psicoterapia/estatística & dados numéricos , Síndrome de Imunodeficiência Adquirida/epidemiologia , Adulto , Idoso , Aconselhamento/estatística & dados numéricos , Feminino , Grécia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Transtornos Mentais/reabilitação , Saúde Mental , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Autoimagem , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/reabilitação , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Inquéritos e Questionários
16.
Dtsch Med Wochenschr ; 144(16): 1158-1165, 2019 08.
Artigo em Alemão | MEDLINE | ID: mdl-31416108

RESUMO

According to the Robert Koch Institute, the estimated HIV prevalence in Germany is 86 100. On-third of the affected persons is over 50 years old. Overall, the prognosis of patients with HIV infection depends crucially on the time of diagnosis. The unfounded stigmatization of affected patients stands in the way of today's treatment options as it did 30 years ago. Every practice of primary care must also take into consideration the medical care of HIV-infected people. The purpose of this article is to make the general practitioner aware of this topic and to prepare for the necessary procedure in everyday practice in this rare but not unlikely situation.


Assuntos
Infecções por HIV , Adulto , Fármacos Anti-HIV/uso terapêutico , Alemanha/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Médicos de Atenção Primária , Prevalência , Prognóstico
17.
Cell Mol Life Sci ; 76(24): 4869-4886, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31377844

RESUMO

The chemokine system mediates acute inflammation by driving leukocyte migration to damaged or infected tissues. However, elevated expression of chemokines and their receptors can contribute to chronic inflammation and malignancy. Thus, great effort has been taken to target these molecules. The first hint of the druggability of the chemokine system was derived from the role of chemokine receptors in HIV infection. CCR5 and CXCR4 function as essential co-receptors for HIV entry, with the former accounting for most new HIV infections worldwide. Not by chance, an anti-CCR5 compound, maraviroc, was the first FDA-approved chemokine receptor-targeting drug. CCR5, by directing leukocytes to sites of inflammation and regulating their activation, also represents an important player in the inflammatory response. This function is shared with CCR2 and its selective ligand CCL2, which constitute the primary chemokine axis driving the recruitment of monocytes/macrophages to inflammatory sites. Both receptors are indeed involved in the pathogenesis of several immune-mediated diseases, and dual CCR5/CCR2 targeting is emerging as a more efficacious strategy than targeting either receptor alone in the treatment of complex human disorders. In this review, we focus on the distinctive and complementary contributions of CCR5 and CCR2/CCL2 in HIV infection, multiple sclerosis, liver fibrosis and associated hepatocellular carcinoma. The emerging therapeutic approaches based on the inhibition of these chemokine axes are highlighted.


Assuntos
Quimiocina CCL2/genética , Inflamação/genética , Receptores CCR2/genética , Receptores CCR5/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Marcação de Genes , HIV/genética , HIV/patogenicidade , Infecções por HIV/genética , Infecções por HIV/terapia , Infecções por HIV/virologia , Humanos , Inflamação/terapia , Cirrose Hepática/genética , Cirrose Hepática/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Esclerose Múltipla/genética , Esclerose Múltipla/terapia
18.
Rev Esc Enferm USP ; 53: e03478, 2019 Jul 29.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31365725

RESUMO

OBJECTIVE: To analyze the social representations of health professionals regarding the care of people living with HIV. METHOD: A descriptive and exploratory study with a qualitative approach in light of the Theory of Social Representations, carried out with health professionals. The semi-structured interview technique was used, which was analyzed using the lexical content analysis technique. RESULTS: Forty-six (46) professionals participated. The analyzed results reveal that the representations and care practices referred to by health professionals are technical, relational and organizational, ensuring the confidentiality of the diagnosis and taking care to develop embracement actions, provide guidance, clarification and emotional and psychological support, as well as being based on confidentiality, multi-professional care practice and addressing structural difficulties. CONCLUSION: It is important to encourage multiprofessional care for people living with HIV, so that professionals engage, develop critical thinking and are able to act in improving healthcare services.


Assuntos
Assistência à Saúde/organização & administração , Infecções por HIV/terapia , Pessoal de Saúde/organização & administração , Adulto , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Teoria Social
19.
Tex Med ; 115(8): e1, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31381809

RESUMO

Much of the southern United States is characterized by unique social, structural, and political systems that may relate to increased stress and poor health outcomes for those living with HIV. Notably, research indicates that Texas has higher survival rates for human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) than general southern trends, which might suggest that Texans living with HIV experience HIV-related stressors and coping strategies influential to health differently than those living elsewhere in the South. This study used grounded theory and semi-structured interviews to increase understanding of HIV-related stress in Texas. Participants (N=20) were 12 people living with HIV in Texas and 8 HIV-care providers in Texas. Results indicated 5 emergent stress-related themes: housing strain, substance use, limited financial abilities, relationship dynamics, and internal pressures and psychosocial resiliency. Results also highlighted some of the potentially unique ways in which this sample experienced these themes, which may relate to relatively better HIV-related outcomes in Texas. Overall, our findings deepen understanding of how people living with HIV in Texas may experience stress and inform potential approaches to HIV care elsewhere.


Assuntos
Assistência à Saúde/estatística & dados numéricos , Infecções por HIV/psicologia , Estresse Psicológico/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Pesquisa Qualitativa , Estigma Social , Fatores Socioeconômicos , Texas/epidemiologia
20.
Scand J Immunol ; 90(5): e12808, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31322752

RESUMO

CD4+ T cell immunotherapy has potential for treatment in HIV-infected patients. A large number of expanded CD4+ T cells and confirmation of functional-related phenotypes are required for ensuring the successful outcomes of treatment. Freshly isolated CD4+ T cells from healthy donors were activated with anti-CD3/28-coated magnetic beads at different bead-to-cell ratios and cultured in the absence and presence of IL-2 supplementation for 3 weeks. Fold expansion, cell viability, growth kinetic and lymphocyte subset identities were determined. Data demonstrated that a 1:1 bead-to-cell ratio rendered the highest expansion of 1044-fold with 88% viability and 99.5% purity followed by the 2:1 and 0.5:1 ratios. No significant difference in proliferation and phenotypes was found between non-IL-2 and IL-2 supplementation groups. Several specific surface molecule expressions of the expanded cells including chemokine receptors, adhesion molecules, co-stimulatory molecules, activation molecules, maturation markers, cytokine receptors and other molecules were altered when compared to the unexpanded cells. This optimized expansion protocol using the 1:1 bead-to-cell ratio of anti-CD3/28-coated magnetic beads and culture condition without IL-2 supplementation provided the satisfactory yield with good reproducibility. Specific surface molecule expressions of the expanded cells presented potential roles in proliferation, differentiation, homeostasis, apoptosis and organ homing.


Assuntos
Antígenos CD28/imunologia , Complexo CD3/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Infecções por HIV/terapia , Imunoterapia Adotiva/métodos , Nanopartículas de Magnetita/uso terapêutico , Adulto , Proliferação de Células , Células Cultivadas , Materiais Revestidos Biocompatíveis , Humanos , Interleucina-2/imunologia , Ativação Linfocitária/imunologia , Resultado do Tratamento
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