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[PMID]:29211347
[Au] Autor:Tanuma J; Matsumoto S; Haneuse S; Cuong DD; Vu TV; Thuy PTT; Dung NT; Dung NTH; Trung NV; Kinh NV; Oka S
[Ad] Endereço:AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
[Ti] Título:Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.
[So] Source:J Int AIDS Soc;20(4), 2017 Dec.
[Is] ISSN:1758-2652
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Achieving viral suppression is key in the global strategy to end the HIV epidemic. However, the levels of viral suppression have yet to be described in many resource-limited settings. METHODS: We investigated the time to virologic failure (VF; defined as a viral load of ≥1000 copies/ml) and changes in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired early immune recovery (defined as not attaining an increase in 100 cells/mm in CD4 counts at 24 months) were further analysed. RESULTS: From 1806 participants, 225 were identified as having VF at a median of 50 months of first-line ART. The viral suppression rate at 12 months was 95.5% and survival without VF was maintained above 90% until 42 months. An increase in CD4 counts from the baseline was greater in groups with lower baseline CD4 counts. A younger age (multivariate hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR 1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT)) were associated with earlier VF. Factors associated with impaired early immune recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. CONCLUSION: Durable high-rate viral suppression was observed in the cohort of patients on first-line ART in Vietnam. Our results highlight the need to increase adherence support among injection drug users and HCV co-infected patients.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Infecções por HIV/tratamento farmacológico
Carga Viral
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Benzoxazinas/uso terapêutico
Contagem de Linfócito CD4
Estudos de Coortes
Feminino
Seres Humanos
Estudos Longitudinais
Masculino
Meia-Idade
Nevirapina/uso terapêutico
Estavudina/uso terapêutico
Fatores de Tempo
Vietnã
Adulto Jovem
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); 4B9XT59T7S (Zidovudine); 99DK7FVK1H (Nevirapine); BO9LE4QFZF (Stavudine); JE6H2O27P8 (efavirenz)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1002/jia2.25030


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[PMID]:29157621
[Au] Autor:Lurain K; Yarchoan R; Uldrick TS
[Ad] Endereço:HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892-1868, USA.
[Ti] Título:Treatment of Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease.
[So] Source:Hematol Oncol Clin North Am;32(1):75-88, 2018 02.
[Is] ISSN:1558-1977
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a rare, polyclonal lymphoproliferative disorder characterized by flares of inflammatory symptoms, edema, cytopenias, lymphadenopathy, and splenomegaly. Diagnosis requires a lymph node biopsy. Pathogenesis is related to dysregulated inflammatory cytokines, including human and viral interleukin-6. Rituximab alone or in combination with chemotherapy, such as liposomal doxorubicin, has led to an overall survival of over 90% at 5 years. Experimental approaches to treatment include virus activated cytotoxic therapy with high-dose zidovudine and valganciclovir and targeting human interleukin-6 activity. Despite successful treatment of KSHV-MCD, patients remain at high risk for developing non-Hodgkin lymphomas.
[Mh] Termos MeSH primário: Doença de Castleman/tratamento farmacológico
Doxorrubicina/uso terapêutico
Ganciclovir/análogos & derivados
Herpesvirus Humano 8
Rituximab/uso terapêutico
Zidovudina/uso terapêutico
[Mh] Termos MeSH secundário: Biópsia
Doença de Castleman/diagnóstico
Doença de Castleman/metabolismo
Doença de Castleman/patologia
Ganciclovir/uso terapêutico
Seres Humanos
Interleucina-6/antagonistas & inibidores
Interleucina-6/metabolismo
Linfonodos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (IL6 protein, human); 0 (Interleukin-6); 4B9XT59T7S (Zidovudine); 4F4X42SYQ6 (Rituximab); 80168379AG (Doxorubicin); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171122
[St] Status:MEDLINE


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[PMID]:29351333
[Au] Autor:Ramírez-Ramírez A; Sánchez-Serrano E; Loaiza-Flores G; Plazola-Camacho N; Rodríguez-Delgado RG; Figueroa-Damián R; Domínguez-Castro M; López-Martínez M; Flores-García Z; Hernández-Pineda J
[Ad] Endereço:Departement of Infectology and Immunology, National Institute of Perinatology, Mexico City, Mexico.
[Ti] Título:Simultaneous quantification of four antiretroviral drugs in breast milk samples from HIV-positive women by an ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method.
[So] Source:PLoS One;13(1):e0191236, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We validated this method following Mexican and international guidelines. ARV drugs. We extracted the ARV drugs from 200 µL samples of breast milk and detected these drugs in a triple quadrupole mass spectrometer with positive electrospray ionization. The validated concentration ranges (ng/mL) for zidovudine, lamivudine, lopinavir, and ritonavir were 12.5-750, 50-2500, 100-5000 and 5 to 250, respectively. Additionally, the absolute recovery percentages (and matrix effects) were 91.4 (8.39), 88.78 (28.75), 91.38 (11.77) and 89.78 (12.37), respectively. We determined that ARV drugs are stable for 24 h at 8°C and 24°C for 15 days at -80°C. This methodology had the capacity for simultaneous detection; separation; and accurate, precise quantification of ARV drugs in human breast milk samples according to Mexican standard laws and United States Food and Drug Administration guidelines.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/análise
Terapia Antirretroviral de Alta Atividade
Infecções por HIV/complicações
Infecções por HIV/tratamento farmacológico
Leite Humano/química
Complicações Infecciosas na Gravidez/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Fármacos Anti-HIV/normas
Aleitamento Materno
Calibragem
Cromatografia Líquida de Alta Pressão/métodos
Cromatografia Líquida de Alta Pressão/normas
Colostro/química
Feminino
Infecções por HIV/prevenção & controle
Seres Humanos
Recém-Nascido
Transmissão Vertical de Doença Infecciosa/prevenção & controle
Lamivudina/análise
Lopinavir/análise
Gravidez
Complicações Infecciosas na Gravidez/metabolismo
Padrões de Referência
Reprodutibilidade dos Testes
Ritonavir/análise
Espectrometria de Massas em Tandem/métodos
Espectrometria de Massas em Tandem/normas
Adulto Jovem
Zidovudina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Anti-HIV Agents); 2494G1JF75 (Lopinavir); 2T8Q726O95 (Lamivudine); 4B9XT59T7S (Zidovudine); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191236


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[PMID]:29323840
[Au] Autor:Galegov GA
[Ti] Título:Phosphazide (nikavir) is a highly effective drug for the treatment of HIV/AIDS infection.
[So] Source:Vopr Virusol;62(1):5-11, 2017.
[Is] ISSN:0507-4088
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:Federation Convincing evidence for high therapeutic activity and tolerability of Phosphazide in the treatment of HIV/AIDS-infection is given. Phosphazide is currently used in various regimens of highly active antiretroviral therapy, as well as in the HIV therapy in patients with simultaneously acquired chronic hepatitis C or tuberculosis. Therapeutic possibilities of Phosphazide were clearly manifested in the prevention of HIV transmission from mother to child. There is every reason to use Phosphazide in first-line antiretroviral therapy.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Infecções por HIV/tratamento farmacológico
HIV/efeitos dos fármacos
Transmissão Vertical de Doença Infecciosa/prevenção & controle
Organofosfonatos/uso terapêutico
Complicações Infecciosas na Gravidez/tratamento farmacológico
Zidovudina/análogos & derivados
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/farmacocinética
Terapia Antirretroviral de Alta Atividade/métodos
Feminino
Feto
HIV/genética
HIV/metabolismo
Infecções por HIV/transmissão
Infecções por HIV/virologia
Seres Humanos
Organofosfonatos/farmacocinética
Gravidez
Complicações Infecciosas na Gravidez/virologia
Resultado do Tratamento
Zidovudina/farmacocinética
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (3'-azido-2',3'-dideoxythymidine 5'-H-phoshonate); 0 (Anti-HIV Agents); 0 (Organophosphonates); 4B9XT59T7S (Zidovudine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


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[PMID]:27776039
[Au] Autor:Brennan AT; Davies MA; Bor J; Wandeler G; Stinson K; Wood R; Prozesky H; Tanser F; Fatti G; Boulle A; Sikazwe I; Wool-Kaloustian K; Yuannoutsos C; Leroy V; de Rekeneire N; Fox MP
[Ad] Endereço:aDepartment of Global Health, Boston University, Boston, Massachusetts, USA bHealth Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa cDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA dCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa eDepartment of Infectious Diseases, Bern University Hospital, University of Bern fInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland gThe Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town hDivision of Infectious Diseases, Department of Medicine, University of Stellenbosch & Tygerberg Academic Hospital, Cape Town iAfrica Center for Health and Population Studies, University of Kwazulu-Natal jKheth'Impilo AIDS Free Living, Cape Town kDepartment of Health, Provincial Government of the Western Cape, Cape Town, South Africa lCenter for Infectious Disease Research in Zambia, Lusaka, Zambia mIndiana University School of Medicine, Indianapolis nRichard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA oINSERM U1027, Université Paul Sabatier Toulouse 3, Toulouse pUniversité Bordeaux, ISPED, Centre INSERM U1219 Epidémiologie-Biostatistique, Bordeaux, France.
[Ti] Título:Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?
[So] Source:AIDS;31(1):147-157, 2017 Jan 02.
[Is] ISSN:1473-5571
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa. DESIGN: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART. METHODS: We evaluated the frequency of stavudine use and SDS by calendar year 2004-2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART. RESULTS: In all, 33 441 (8.9%; 95% confience interval 8.7-8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20-95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75-85% decrease in the hazards of SDS when compared to stavudine. CONCLUSION: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Terapia Antirretroviral de Alta Atividade/métodos
Substituição de Medicamentos
Infecções por HIV/tratamento farmacológico
Estavudina/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
África ao Sul do Saara
Uso de Medicamentos
Feminino
Política de Saúde
Seres Humanos
Masculino
Estudos Prospectivos
Tenofovir/uso terapêutico
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 4B9XT59T7S (Zidovudine); 99YXE507IL (Tenofovir); BO9LE4QFZF (Stavudine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28763473
[Au] Autor:Gianotti N; Poli A; Galli L; Franzin M; Tadini P; Galizzi N; Carbone A; Merli M; Muccini C; Oltolini C; Andolina A; Spagnuolo V; Lazzarin A; Castagna A
[Ad] Endereço:Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.
[Ti] Título:Efficacy and safety of switching from branded to generic antiretrovirals in virologically suppressed HIV-infected patients.
[So] Source:PLoS One;12(8):e0182007, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Aim of this study was to evaluate the efficacy and the safety of switching from branded to generic antiretrovirals in patients with HIV-RNA <50 copies/mL. METHODS: Matched-cohort study of patients followed at a single clinical center. Since September 2014, all patients with HIV-RNA <50 copies/mL who were receiving branded lamivudine or zidovudine/lamivudine or efavirenz were switched to the generic compound (switchers) and matched, in a ratio 1:1, for age (±5 years), gender, anti-HCV antibodies, nadir and (±50 cells/µL) baseline CD4+ count (±100 cells/µL), duration of antiretroviral therapy (±1 year), with patients with HIV-RNA <50 copies/mL, on treatment with unavailable generic compounds (non-switchers). Incidence rates (IR) of different outcomes were calculated and compared by Poisson regression model. A confirmed HIV-RNA ≥50 copies/mL defined virological failure; any change in the antiretroviral regimen was defined as treatment discontinuation. RESULTS: Four hundred forty patients were switched to generic compounds (268 [61%] on lamivudine, 65 [15%] on zidovudine/lamivudine, 87 [20%] on efavirenz and 20 [4%] on efavirenz and either lamivudine or zidovudine/lamivudine). Over a median follow-up of 15.0 (12.1-15.7) months, virological failure occurred in four switchers (IR: 0.07 [0.02-0.18]/100-person months of follow-up [PMFU]) and in ten non-switchers (IR: 0.20 [0.10-0.35]/100-PMFU) (p = 0.0003), while treatment discontinuation occurred in 118 switchers (IR: 2.05 [1.70-2.44]/100-PMFU) and in 128 non-switchers (IR: 2.37 [1.99-2.81]/100-PMFU) (p = 0.699). CONCLUSIONS: After more than one year of follow-up, we found no evidence of increased risk of reduced efficacy or increased toxicity after switching from branded to generic lamivudine or zidovudine/lamivudine or efavirenz.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Medicamentos Genéricos/uso terapêutico
Infecções por HIV/tratamento farmacológico
[Mh] Termos MeSH secundário: Benzoxazinas/uso terapêutico
Estudos de Coortes
Didesoxinucleosídeos/uso terapêutico
Combinação de Medicamentos
Quimioterapia Combinada
Feminino
Seguimentos
HIV-1
Seres Humanos
Lamivudina/uso terapêutico
Masculino
Meia-Idade
Segurança do Paciente
Distribuição de Poisson
RNA Viral
Resultado do Tratamento
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); 0 (Dideoxynucleosides); 0 (Drug Combinations); 0 (Drugs, Generic); 0 (RNA, Viral); 0 (lamivudine, zidovudine drug combination); 2T8Q726O95 (Lamivudine); 4B9XT59T7S (Zidovudine); JE6H2O27P8 (efavirenz)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182007


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[PMID]:28753637
[Au] Autor:Paredes R; Tzou PL; van Zyl G; Barrow G; Camacho R; Carmona S; Grant PM; Gupta RK; Hamers RL; Harrigan PR; Jordan MR; Kantor R; Katzenstein DA; Kuritzkes DR; Maldarelli F; Otelea D; Wallis CL; Schapiro JM; Shafer RW
[Ad] Endereço:IrsiCaixa AIDS Research Institute, Badalona, Spain.
[Ti] Título:Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation.
[So] Source:PLoS One;12(7):e0181357, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve. METHODS: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations. The DRM pattern-ARV combinations included 52 nucleoside RT inhibitor (NRTI) DRM pattern-ARV combinations (13 patterns x 4 NRTIs), 27 nonnucleoside RT inhibitor (NNRTI) DRM pattern-ARV combinations (9 patterns x 3 NNRTIs), 39 protease inhibitor (PI) DRM pattern-ARV combinations (13 patterns x 3 PIs) and 42 integrase strand transfer inhibitor (INSTI) DRM pattern-ARV combinations (14 patterns x 3 INSTIs). RESULTS: There was universal agreement that a GRT report should include the NRTIs lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir disoproxil fumarate; the NNRTIs efavirenz, etravirine, nevirapine, and rilpivirine; the PIs atazanavir/r, darunavir/r, and lopinavir/r (with "/r" indicating pharmacological boosting with ritonavir or cobicistat); and the INSTIs dolutegravir, elvitegravir, and raltegravir. There was a range of opinion as to whether the NRTIs stavudine and didanosine and the PIs nelfinavir, indinavir/r, saquinavir/r, fosamprenavir/r, and tipranavir/r should be included. The expert panel members provided highly concordant DRM pattern-ARV interpretations with only 6% of NRTI, 6% of NNRTI, 5% of PI, and 3% of INSTI individual expert interpretations differing from the expert panel median by more than one resistance level. The expert panel median differed from the HIVDB 7.0 GRT-IS for 20 (12.5%) of the 160 DRM pattern-ARV combinations including 12 NRTI, two NNRTI, and six INSTI pattern-ARV combinations. Eighteen of these differences were updated in HIVDB 8.1 GRT-IS to reflect the expert panel median. Additionally, HIVDB users are now provided with the option to exclude those ARVs not considered to be universally required. CONCLUSIONS: The HIVDB GRT-IS was updated through a collaborative process to reflect changes in HIV drug resistance knowledge, treatment guidelines, and expert opinion. Such a process broadens consensus among experts and identifies areas requiring further study.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacologia
HIV-1/efeitos dos fármacos
HIV-1/genética
Inibidores da Transcriptase Reversa/farmacologia
[Mh] Termos MeSH secundário: Benzoxazinas/farmacologia
Didesoxinucleosídeos/farmacologia
Farmacorresistência Viral/genética
Genótipo
Compostos Heterocíclicos com 3 Anéis/farmacologia
Lamivudina/farmacologia
Lopinavir/farmacologia
Nelfinavir/farmacologia
Ritonavir/farmacologia
Zidovudina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); 0 (Dideoxynucleosides); 0 (Heterocyclic Compounds, 3-Ring); 0 (Reverse Transcriptase Inhibitors); 2494G1JF75 (Lopinavir); 2T8Q726O95 (Lamivudine); 4B9XT59T7S (Zidovudine); DKO1W9H7M1 (dolutegravir); HO3OGH5D7I (Nelfinavir); JE6H2O27P8 (efavirenz); O3J8G9O825 (Ritonavir); WR2TIP26VS (abacavir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171007
[Lr] Data última revisão:
171007
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181357


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[PMID]:28712845
[Au] Autor:Namanja-Magliano HA; Bohn K; Agrawal N; Willoughby ME; Hrycyna CA; Chmielewski J
[Ad] Endereço:Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
[Ti] Título:Dual inhibitors of the human blood-brain barrier drug efflux transporters P-glycoprotein and ABCG2 based on the antiviral azidothymidine.
[So] Source:Bioorg Med Chem;25(19):5128-5132, 2017 Oct 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The brain provides a sanctuary site for HIV due, in part, to poor penetration of antiretroviral agents at the blood-brain barrier. This lack of penetration is partially attributed to drug efflux transporters such as P-glycoprotein (P-gp) and ABCG2. Inhibition of both ABCG2 and P-gp is critical for enhancing drug accumulation into the brain. In this work, we have developed a class of homodimers based on the HIV reverse transcriptase inhibitor azidothymidine (AZT) that effectively inhibits P-gp and ABCG2. These agents block transporter mediated efflux of the P-gp substrate calcein-AM and the ABCG2 substrate mitoxantrone. The homodimers function by interacting with the transporter drug binding sites as demonstrated by competition studies with the photo-affinity agent and P-gp/ABCG2 substrate [ I]iodoarylazidoprazosin. As such, these dual inhibitors of both efflux transporters provide a model for the future development of delivery vehicles for antiretroviral agents to the brain.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores
Transporte Biológico/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Proteínas de Neoplasias/antagonistas & inibidores
Zidovudina/análogos & derivados
Zidovudina/farmacologia
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Antivirais/química
Antivirais/farmacologia
Barreira Hematoencefálica/metabolismo
Linhagem Celular
Dimerização
Seres Humanos
Proteínas de Neoplasias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Antiviral Agents); 0 (Neoplasm Proteins); 4B9XT59T7S (Zidovudine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE


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[PMID]:28707345
[Au] Autor:Hofer CB; Egger M; Davies MA; Frota ACC; de Oliveira RH; Abreu TF; Araújo LE; Witthlin BB; Carvalho AW; Cordeiro JR; Lima GP; Keiser O
[Ad] Endereço:Institute of Social and Preventive Medicine, Berne University, Berne, Switzerland.
[Ti] Título:The cascade of care to prevent mother-to-child transmission in Rio de Janeiro, Brazil, 1996-2013: improving but still some way to go.
[So] Source:Trop Med Int Health;22(10):1266-1274, 2017 Oct.
[Is] ISSN:1365-3156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To describe the cascade of care to HIV mother-to-child transmission (PMTCT) in a Rio de Janeiro reference paediatric clinic and evaluate the main factors possibly associated with HIV transmission. METHODS: Data on antenatal care (ANC), perinatal and neonatal assistance to HIV-infected and HIV-exposed but uninfected children assisted in the clinic from 1996 to 2013 were collected. The cascade of care was graphically demonstrated, and possible factors associated with HIV infection were described using regression models for bivariate and multivariate analysis. We imputed missing values of explanatory variables for the final model. RESULTS: A total of 989 children were included in the analysis: 211 were HIV and 778 HEU. Graphically, the HIV PMTCT cascade of care improved from 1996/2000 to the later periods, but not from 2001/2006 to 2007/2013. The main factor independently associated with the HIV infection over time was breastfeeding. In the period 1996/2000, the lack of antiretroviral use during labour was associated HIV transmission. While in 2001/2007, other modes of delivery but elective Caesarean section, and lack of maternal antiretroviral use during ANC were associated with HIV transmission. In the last period, the main factor associated with transmission was the lack of maternal ANC. CONCLUSIONS: The HIV PMTCT cascade improved over time, but HIV vertical transmission remains a problem, and better access to ANC is needed.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Aleitamento Materno
Infecções por HIV/psicologia
Transmissão Vertical de Doença Infecciosa/prevenção & controle
Complicações Infecciosas na Gravidez/tratamento farmacológico
Cuidado Pré-Natal/métodos
Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
Zidovudina/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Fármacos Anti-HIV/provisão & distribuição
Brasil
Aleitamento Materno/efeitos adversos
Contraindicações
Feminino
Infecções por HIV/tratamento farmacológico
Infecções por HIV/transmissão
Seres Humanos
Lactente
Fórmulas Infantis/provisão & distribuição
Recém-Nascido
Idade Materna
Gravidez
Cuidado Pré-Natal/normas
Carga Viral
Adulto Jovem
Zidovudina/provisão & distribuição
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 4B9XT59T7S (Zidovudine); 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1111/tmi.12925


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[PMID]:28705594
[Au] Autor:Filia MF; Marchini T; Minoia JM; Roma MI; De Fino FT; Rubio MC; Copello GJ; Evelson PA; Peroni RN
[Ad] Endereço:Instituto de Investigaciones Farmacológicas (ININFA UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 5°, 1113 Ciudad Autónoma de Buenos Aires, Argentina.
[Ti] Título:Induction of ABCG2/BCRP restricts the distribution of zidovudine to the fetal brain in rats.
[So] Source:Toxicol Appl Pharmacol;330:74-83, 2017 Sep 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Safety concerns for fetus development of zidovudine (AZT) administration as prophylaxis of vertical transmission of HIV persist. We evaluated the participation of the ATP-binding cassette efflux transporter ABCG2 in the penetration of AZT into the fetal brain and the relevance for drug safety. Oral daily doses of AZT (60mg/kg body weight) or its vehicle were administered between post gestational days 11 (E11) and 20 (E20) to Sprague-Dawley pregnant rats. At E21, animals received an intravenous bolus of 60mg AZT/kg body weight in the presence or absence of the ABCG2 inhibitor gefitinib (20mg/kg body weight, ip) and AZT in maternal plasma and fetal brain were measured by HPLC-UV. ABCG2 protein expression in placenta and fetal brain, as well as mitochondrial function and ultrastructure in fetal brain were also analyzed. In utero chronic exposure to AZT markedly induced ABCG2 expression in placenta and fetal brain whereas did not significantly alter mitochondrial functionality in the fetal brain. The area-under-the-concentration-time-curve of AZT significantly decreased in fetal brains isolated from AZT-exposed fetuses compared to control group, but this effect was abolished by ABCG2 inhibition. Our results suggest that the absence of mitochondrial toxicity in the fetal brain after chronic in utero administration of AZT could be attributed to its low accumulation in the tissue caused, at least in part, by ABCG2 overexpression. We propose that any interference with ABCG2 activity due to genetic, pathological or iatrogenic factors would increase the amount of AZT reaching the fetal brain, which could increase the risk of toxicity of this drug on the tissue.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese
Fármacos Anti-HIV/farmacocinética
Encéfalo/metabolismo
Inibidores da Transcriptase Reversa/farmacocinética
Zidovudina/farmacocinética
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
Animais
Fármacos Anti-HIV/farmacologia
Disponibilidade Biológica
Encéfalo/efeitos dos fármacos
Feminino
Feto/efeitos dos fármacos
Feto/metabolismo
Peroxidação de Lipídeos/efeitos dos fármacos
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Mitocôndrias/ultraestrutura
Gravidez
Quinazolinas/farmacologia
Ratos
Ratos Sprague-Dawley
Inibidores da Transcriptase Reversa/farmacologia
Zidovudina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Abcg2 protein, rat); 0 (Anti-HIV Agents); 0 (Quinazolines); 0 (Reverse Transcriptase Inhibitors); 4B9XT59T7S (Zidovudine); S65743JHBS (gefitinib)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE



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