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[PMID]:28461133
[Au] Autor:Chen DJ; Yao JD
[Ad] Endereço:Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. Electronic address: dchen@uwhealth.org.
[Ti] Título:Comparison of turnaround time and total cost of HIV testing before and after implementation of the 2014 CDC/APHL Laboratory Testing Algorithm for diagnosis of HIV infection.
[So] Source:J Clin Virol;91:69-72, 2017 06.
[Is] ISSN:1873-5967
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Updated recommendations for HIV diagnostic laboratory testing published by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories incorporate 4th generation HIV immunoassays, which are capable of identifying HIV infection prior to seroconversion. OBJECTIVES: The purpose of this study was to compare turnaround time and cost between 3rd and 4th generation HIV immunoassay-based testing algorithms for initially reactive results. STUDY DESIGN: The clinical microbiology laboratory database at Mayo Clinic, Rochester, MN was queried for 3rd generation (from November 2012 to May 2014) and 4th generation (from May 2014 to November 2015) HIV immunoassay results. All results from downstream supplemental testing were recorded. Turnaround time (defined as the time of initial sample receipt in the laboratory to the time the final supplemental test in the algorithm was resulted) and cost (based on 2016 Medicare reimbursement rates) were assessed. RESULTS: A total of 76,454 and 78,998 initial tests were performed during the study period using the 3rd generation and 4th generation HIV immunoassays, respectively. There were 516 (0.7%) and 581 (0.7%) total initially reactive results, respectively. Of these, 304 (58.9%) and 457 (78.7%) were positive by supplemental testing. There were 10 (0.01%) cases of acute HIV infection identified with the 4th generation algorithm. The most frequent tests performed to confirm an HIV-positive case using the 3rd generation algorithm, which were reactive initial immunoassay and positive HIV-1 Western blot, took a median time of 1.1 days to complete at a cost of $45.00. In contrast, the most frequent tests performed to confirm an HIV-positive case using the 4th generation algorithm, which included a reactive initial immunoassay and positive HIV-1/-2 antibody differentiation immunoassay for HIV-1, took a median time of 0.4 days and cost $63.25. Overall median turnaround time was 2.2 and 1.5 days, and overall median cost was $63.90 and $72.50 for 3rd and 4th generation algorithms, respectively. CONCLUSIONS: Both 3rd and 4th generation HIV immunoassays had similar total numbers of tests performed and positivity rates during the study period. A greater proportion of reactive 4th generation immunoassays were confirmed to be positive, and the 4th generation algorithm identified several cases of acute HIV infection that would have been missed by the 3rd generation algorithm. The 4th generation algorithm had a more rapid turnaround time but higher cost for confirmed positive HIV infections and overall, compared to the 3rd generation algorithm.
[Mh] Termos MeSH primário: Sorodiagnóstico da AIDS
Algoritmos
Infecções por HIV/diagnóstico
Imunoensaio
[Mh] Termos MeSH secundário: Sorodiagnóstico da AIDS/economia
Centers for Disease Control and Prevention (U.S.)
Custos e Análise de Custo
Anticorpos Anti-HIV/sangue
Infecções por HIV/economia
Infecções por HIV/virologia
HIV-1/genética
HIV-1/imunologia
HIV-2/genética
HIV-2/imunologia
Seres Humanos
Imunoensaio/economia
Imunoensaio/métodos
Programas de Rastreamento/economia
Programas de Rastreamento/legislação & jurisprudência
Programas de Rastreamento/métodos
Técnicas de Amplificação de Ácido Nucleico/economia
Técnicas de Amplificação de Ácido Nucleico/métodos
Sensibilidade e Especificidade
Estados Unidos
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Antibodies)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 72404 MEDLINE  
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[PMID]:29381736
[Au] Autor:Jean Louis F; Buteau J; François K; Hulland E; Domerçant JW; Yang C; Boncy J; Burris R; Pelletier V; Wagar N; Deyde V; Lowrance DW; Charles M
[Ad] Endereço:Centers for Disease Control and Prevention, Port-au-Prince, Haiti.
[Ti] Título:Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti.
[So] Source:PLoS One;13(1):e0192077, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Viral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti. METHODS: Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures. RESULTS: Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]). CONCLUSIONS: This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Infecções por HIV/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Pré-Escolar
Feminino
Infecções por HIV/virologia
HIV-1/genética
HIV-1/isolamento & purificação
Haiti
Seres Humanos
Lactente
Recém-Nascido
Masculino
Meia-Idade
RNA Viral/sangue
Carga Viral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (RNA, Viral)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192077


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[PMID]:29346431
[Au] Autor:Pollack TM; Duong HT; Truong PT; Pham TT; Do CD; Colby D
[Ad] Endereço:The Partnership for Health Advancement in Vietnam, Beth Israel Deaconess Medical Center, Hanoi, Vietnam.
[Ti] Título:Sensitivity and specificity of two dried blood spot methods for HIV-1 viral load monitoring among patients in Hanoi, Vietnam.
[So] Source:PLoS One;13(1):e0191411, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is recommended to support the roll-out of routine VL monitoring in low and middle income countries (LMICs). To better understand the use of DBS for VL monitoring, we evaluated two DBS testing methods, Roche TaqMan® Free Virus Evolution protocol (DBS-FVE) and Roche TaqMan® SPEX protocol (DBS-SPEX)) in patients receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each DBS testing method at the thresholds of 1000 and 5000 copies/ml compared to plasma VL. At a threshold of 1000 copies/ml, sensitivity, specificity, PPV and NPV of the DBS-SPEX method were 98.8% (95% CI: 93.3%-100%), 74.3% (95% CI: 70.8%-77.5%), 31.5% (95% CI: 25.8%-37.6%), and 99.8% (95% CI: 98.9%-100%), respectively. Increasing the VL threshold value to 5000 copies/ml improved specificity (97.9% CI: 96.6%-98.9%) and PPV (83.9% CI: 74.5%-90.9%). Using the DBS-FVE method, at the threshold of 1000 copies/ml and with a correction factor of +0.3 log copies/ml, sensitivity was 95.1% (87.8%-98.6%) and specificity was 98.8% (97.7%-99.5%). Sensitivity decreased at the threshold of 5000 copies/ml (65.8%, 95% CI: 54.3%-76.1%). With a correction factor of +0.7 log copies/ml, the sensitivity was 96.3% (89.6%-99.2%) and specificity was 98.2% (96.9%-99.1%) at the threshold of 1000 copies/ml. We found that the Roche DBS-FVE method, with a +0.7 log copies/ml correction factor, performed well with sensitivity and specificity greater than 96% at a VL threshold of 1000 copies/m. These findings add to the growing body of evidence supporting the use of DBS VL testing for ART monitoring. Future research should evaluate the association between VL results by DBS and clinical outcome measures such as HIV drug resistance, morbidity, and mortality.
[Mh] Termos MeSH primário: Infecções por HIV/sangue
Monitorização Fisiológica/métodos
Carga Viral
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Feminino
Infecções por HIV/virologia
HIV-1/isolamento & purificação
Seres Humanos
Masculino
Meia-Idade
Sensibilidade e Especificidade
Vietnã
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191411


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[PMID]:28461065
[Au] Autor:Hu D; Bowder D; Wei W; Thompson J; Wilson MA; Xiang SH
[Ad] Endereço:Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
[Ti] Título:Tryptophan 375 stabilizes the outer-domain core of gp120 for HIV vaccine immunogen design.
[So] Source:Vaccine;35(23):3067-3075, 2017 05 25.
[Is] ISSN:1873-2518
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a striking increase in the immune response due to this stabilized core outer-domain. Therefore, we conclude that the addition of 375W to the outer-domain core of gp120 further stabilizes the structure of immunogen and increases the immunogenicity.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Anti-HIV/imunologia
Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/imunologia
Imunogenicidade da Vacina
Triptofano/química
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/administração & dosagem
Vacinas contra a AIDS/química
Substituição de Aminoácidos
Animais
Anticorpos Neutralizantes/imunologia
Antígenos CD4
Desenho de Drogas
Epitopos/química
Cobaias
Anticorpos Anti-HIV/sangue
HIV-1/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (Epitopes); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp120); 8DUH1N11BX (Tryptophan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  5 / 72404 MEDLINE  
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[PMID]:28453847
[Au] Autor:Khoury G; Fromentin R; Solomon A; Hartogensis W; Killian M; Hoh R; Somsouk M; Hunt PW; Girling V; Sinclair E; Bacchetti P; Anderson JL; Hecht FM; Deeks SG; Cameron PU; Chomont N; Lewin SR
[Ad] Endereço:The Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Australia.
[Ti] Título:Human Immunodeficiency Virus Persistence and T-Cell Activation in Blood, Rectal, and Lymph Node Tissue in Human Immunodeficiency Virus-Infected Individuals Receiving Suppressive Antiretroviral Therapy.
[So] Source:J Infect Dis;215(6):911-919, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence. Methods: Using flow cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48), lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated unspliced HIV RNA were quantified. Results: CD4+ T cells from rectal tissue had a higher frequency of integrated HIV DNA compared with blood (4.26 fold-change in DNA; 95% confidence interval [CI] = 2.61-7.00; P < .001) and LN (2.32 fold-change in DNA; 95% CI = 1.22-4.41; P = .01). In rectal tissue, there were positive associations between integrated HIV DNA with PD-1+ CD4+ T-cells (1.44 fold-change in integrated HIV DNA per 10-unit increase in PD-1+ CD4+ T cells; 95% CI = 1.01-2.05; P = .045) and CD38+HLA-DR+ CD8+ T cells (1.40 fold-change in integrated HIV DNA per 1-unit increase in CD38+HLA-DR+ CD8+ T cells; 95% CI = 1.05-1.86; P = .02). Both associations were independent of current and nadir CD4+ T-cell counts. Conclusions: During ART, rectal tissue is an important reservoir for HIV persistence with a high frequency of activated CD4+ and CD8+ T cells. PD-1 may represent a marker of HIV persistence in rectal tissue.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Infecções por HIV/tratamento farmacológico
Infecções por HIV/imunologia
Ativação Linfocitária
[Mh] Termos MeSH secundário: Terapia Antirretroviral de Alta Atividade
Austrália
Biomarcadores/metabolismo
Contagem de Linfócito CD4
Estudos Transversais
DNA Viral/sangue
Feminino
HIV-1/imunologia
Antígenos HLA-DR/análise
Seres Humanos
Linfonodos/imunologia
Masculino
Meia-Idade
Receptor de Morte Celular Programada 1/metabolismo
Reto/imunologia
Análise de Regressão
Fatores Sexuais
Estados Unidos
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (DNA, Viral); 0 (HLA-DR Antigens); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix039


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[PMID]:28453843
[Au] Autor:Uprety P; Lindsey JC; Levin MJ; Rainwater-Lovett K; Ziemniak C; Bwakura-Dangarembizix M; Kaplan SS; Nelson M; Zadzilka A; Weinberg A; Persaud D
[Ad] Endereço:W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
[Ti] Título:Inflammation and Immune Activation in Antiretroviral-Treated Human Immunodeficiency Virus Type 1-Infected African Infants and Rotavirus Vaccine Responses.
[So] Source:J Infect Dis;215(6):928-932, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Biomarkers of inflammation and immune activation were correlated with rotavirus vaccine responses in 68 human immunodeficiency virus type 1 (HIV-1)­infected (and 116 HIV-exposed but uninfected (HEU) African infants receiving pentavalent rotavirus vaccine (RV5) in a clinical trial. Prevaccination, HIV-1+ infants had significantly higher concentrations of interferon γ (IFNγ), interleukin1ß, interleukin 2, interleukin 6, interleukin 10 (IL-10), and soluble CD14 compared with HEU infants. Postvaccination concentrations of neutralizing antibodies to RV5 were negatively correlated with prevaccination concentrations of IL-10 (RV5 surface proteins G1 and P1) and IFNγ (G1) in the HIV-1+ infants, whereas antirotavirus immunoglobulin A (IgA) levels were not. Heightened inflammation and immune activation in HIV-1+ infants did not alter IgA responses associated with protection from rotavirus disease.
[Mh] Termos MeSH primário: Infecções por HIV/tratamento farmacológico
Infecções por Rotavirus/prevenção & controle
Vacinas contra Rotavirus/uso terapêutico
[Mh] Termos MeSH secundário: Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Terapia Antirretroviral de Alta Atividade
Biomarcadores/sangue
Botsuana
Contagem de Linfócito CD4
Citocinas/sangue
Método Duplo-Cego
Feminino
HIV-1/imunologia
Seres Humanos
Imunoglobulina A/sangue
Lactente
Inflamação
Masculino
Análise Multivariada
Tanzânia
Zâmbia
Zimbábue
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Biomarkers); 0 (Cytokines); 0 (Immunoglobulin A); 0 (Rotavirus Vaccines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix060


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[PMID]:28453835
[Au] Autor:Celum C; Hong T; Cent A; Donnell D; Morrow R; Baeten JM; Firnhaber C; Grinsztejn B; Hosseinipour MC; Lalloo U; Nyirenda M; Riviere C; Sanchez J; Santos B; Supparatpinyo K; Hakim J; Kumarasamy N; Campbell TB; ACTG PEARLS/A5175 Team
[Ad] Endereço:Department of Global Health, University of Washington , Seattle, Washington, USA.
[Ti] Título:Herpes Simplex Virus Type 2 Acquisition Among HIV-1-Infected Adults Treated With Tenofovir Disoproxyl Fumarate as Part of Combination Antiretroviral Therapy: Results From the ACTG A5175 PEARLS Study.
[So] Source:J Infect Dis;215(6):907-910, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Objective: Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2 acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design: Secondary analysis of AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART regimens among 1571 participants. Methods: HSV-2 serostatus was assessed at baseline, at study exit, and before a change in ART regimen. Results: Of 365 HSV-2-seronegative persons, 68 acquired HSV-2, with 24 receiving TDF-containing ART and 44 receiving ART without TDF (HSV-2 seroconversion incidence, 6.42 and 6.63 cases/100 person-years, respectively; hazard ratio, 0.89; 95% confidence interval, .55-1.44). Conclusions: HSV-2 acquisition was not reduced in HIV-infected, HSV-2-uninfected persons during TDF-containing ART.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Infecções por HIV/complicações
Herpes Simples/prevenção & controle
Herpesvirus Humano 2/efeitos dos fármacos
Profilaxia Pré-Exposição
Tenofovir/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Feminino
Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Seres Humanos
Cooperação Internacional
Masculino
Adesão à Medicação
Meia-Idade
Modelos de Riscos Proporcionais
Soroconversão
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antiviral Agents); 99YXE507IL (Tenofovir)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix029


  8 / 72404 MEDLINE  
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[PMID]:28453836
[Au] Autor:Margot NA; Wong P; Kulkarni R; White K; Porter D; Abram ME; Callebaut C; Miller MD
[Ad] Endereço:Gilead Sciences, Foster City, California, USA.
[Ti] Título:Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide.
[So] Source:J Infect Dis;215(6):920-927, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: The presence of transmitted drug resistance mutations (TDRMs) in antiretroviral treatment (ART)-naive patients can adversely affect the outcome of ART. Methods: Resistance testing was conducted in 6704 ART-naive subjects predominantly from the United States and Europe in 9 clinical studies conducted by Gilead Sciences from 2000 to 2013. Results: The presence of TDRMs increased during this period (from 5.2% to 11.4%), primarily driven by an increase in nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations (from 0.3% to 7.1%), particularly K103N/S (increase from 0.3% to 5.3%). Nucleoside/nucleotide RT inhibitor mutations were found in 3.1% of patients. Only 1 patient had K65R (0.01%) and 7 had M184V/I (0.1%), despite high use of tenofovir disoproxil fumarate (TDF), emtricitabine, and lamivudine and potential transmission of resistance to these drugs. At least 1 thymidine-analogue mutations was present in 2.7% of patients with 0.07% harboring T215Y/F and 2.7% harboring T215 revertant mutations (T215rev). Patients with the combination of M41L + L210W + T215rev showed full human immunodeficiency virus RNA suppression while receiving a TDF- or tenofovir alafenamide-containing regimen. Conclusions: There was an overall increase of TDRMs among patients enrolling in clinical trials from 2000 through 2013, driven primarily by an increase in NNRTI resistance. However, the presence of common TDRMs, including thymidine-analogue mutations/T215rev, showed no impact on response to TDF- or tenofovir alafenamide-containing regimens.
[Mh] Termos MeSH primário: Adenina/análogos & derivados
Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral/genética
Infecções por HIV/tratamento farmacológico
HIV-1/genética
Tenofovir/uso terapêutico
[Mh] Termos MeSH secundário: Adenina/uso terapêutico
Adulto
Emtricitabina/uso terapêutico
Europa (Continente)
Feminino
HIV-1/efeitos dos fármacos
Seres Humanos
Lamivudina/uso terapêutico
Masculino
Mutação de Sentido Incorreto
Inibidores da Transcriptase Reversa/uso terapêutico
Timidina/análogos & derivados
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (GS-7340); 0 (Reverse Transcriptase Inhibitors); 2T8Q726O95 (Lamivudine); 99YXE507IL (Tenofovir); G70B4ETF4S (Emtricitabine); JAC85A2161 (Adenine); VC2W18DGKR (Thymidine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix015


  9 / 72404 MEDLINE  
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[PMID]:29246084
[Au] Autor:Capetti AF; Cossu MV; Paladini L; Rizzardini G
[Ad] Endereço:a First Division of Infectious Diseases , ASST Fatebenefratelli-Sacco , Milano , Italy.
[Ti] Título:Dolutegravir plus rilpivirine dual therapy in treating HIV-1 infection.
[So] Source:Expert Opin Pharmacother;19(1):65-77, 2018 Jan.
[Is] ISSN:1744-7666
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The HIV-infected population is aging and comorbidities and polypharmacological regimens are increasing. To reduce toxicity and drug burden researchers are evaluating the efficacy, safety and durability of dual therapies as a switch option in subjects who have achieved stable virologic suppression. Initially effective dual combinations relied on protease inhibitors but when dolutegravir, the first integrase inhibitor to display a high genetic barrier, became commercially available, many physicians began to use it in a variety of dual regimens, generating several observational cohorts. Areas covered: This review covers the most recent data from observational cohorts and randomized clinical trials concerning the switch to the dual combination of dolutegravir plus rilpivirine and the reasons that lead to consider this option. Also, viral failures, due to poor adherence or to other factors, and drug resistance are investigated. Articles which are searchable on MEDLINE/PubMed and from the main national/international congresses in the field of HIV therapy are reviewed. Expert opinion: The observation period for this regimen is getting longer and data showing its efficacy in maintaining HIV-1 RNA < 50 copies/mL are now consolidated. Metabolic data suggest some benefit in the lipid profile, improvement in bone mineral density and reduced bone reabsorption.
[Mh] Termos MeSH primário: Infecções por HIV/tratamento farmacológico
Compostos Heterocíclicos com 3 Anéis/administração & dosagem
Rilpivirina/administração & dosagem
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/uso terapêutico
Quimioterapia Combinada
HIV-1/efeitos dos fármacos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Heterocyclic Compounds, 3-Ring); DKO1W9H7M1 (dolutegravir); FI96A8X663 (Rilpivirine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1080/14656566.2017.1417984


  10 / 72404 MEDLINE  
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[PMID]:29180487
[Au] Autor:Pierog PL; Zhao Y; Singh S; Dai J; Yap GS; Fitzgerald-Bocarsly P
[Ad] Endereço:Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103.
[Ti] Título: Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10.
[So] Source:J Immunol;200(1):186-195, 2018 01 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection with on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that invaded but did not induce IFN-α or TNF-α in human pDC. However, inhibited IFN-α and TNF-α produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-α production was inhibited only in cells infected by , which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71 endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-α response was partially reversed by a deficiency in the -derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10's anti-inflammatory effects. Taken together, our results indicate that suppresses pDC activation by mimicking IL-10's regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by and IL-10 and suggest potential negative consequences of HIV/ coinfection.
[Mh] Termos MeSH primário: Células Dendríticas/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Interleucina-10/metabolismo
Infecções Oportunistas/imunologia
Proteínas Tirosina Quinases/metabolismo
Proteínas de Protozoários/metabolismo
Toxoplasma/imunologia
Toxoplasmose/imunologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Células Cultivadas
Coinfecção
Células Dendríticas/parasitologia
Seres Humanos
Imunidade Inata
Imunomodulação
Fator Regulador 7 de Interferon/metabolismo
Interferon-alfa/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
Receptor Toll-Like 9/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (IRF7 protein, human); 0 (Interferon Regulatory Factor-7); 0 (Interferon-alpha); 0 (Protozoan Proteins); 0 (STAT3 Transcription Factor); 0 (Toll-Like Receptor 9); 0 (Tumor Necrosis Factor-alpha); 130068-27-8 (Interleukin-10); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Rop16 protein, Toxoplasma gondii)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1701045



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