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  1 / 105 MEDLINE  
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[PMID]:28525596
[Au] Autor:Hirakawa H; Gatanaga H; Ochi H; Fukuda T; Sunamura S; Oka S; Takeda S; Sato S
[Ad] Endereço:Departments of 1Physiology and Cell Biology.
[Ti] Título:Antiretroviral Therapy Containing HIV Protease Inhibitors Enhances Fracture Risk by Impairing Osteoblast Differentiation and Bone Quality.
[So] Source:J Infect Dis;215(12):1893-1897, 2017 Jun 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long-term antiretroviral therapy is associated with increased fracture risk, but the mechanism remains elusive. We measured serum undercarboxylated osteocalcin and pentosidine (markers of poor bone quality) in human immunodeficiency virus-infected patients treated with protease inhibitors (PIs) or an integrase strand transfer inhibitor-containing regimen. The results demonstrated significantly higher undercarboxylated osteocalcin and pentosidine in PI-treated patients. Switching to integrase strand transfer inhibitor significant decreased these markers. We also showed impaired bone mechanical properties with higher undercarboxylated osteocalcin level in PI-treated mice and inhibited osteoblast differentiation in PI-treated osteogenic cells. The results confirmed the adverse effects of PIs on bone quality and osteoblast differentiation.
[Mh] Termos MeSH primário: Terapia Antirretroviral de Alta Atividade/efeitos adversos
Densidade Óssea/efeitos dos fármacos
Inibidores de Proteases/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Arginina/análogos & derivados
Arginina/sangue
Biomarcadores/sangue
Feminino
HIV-1/efeitos dos fármacos
Seres Humanos
Inibidores de Integrase
Lisina/análogos & derivados
Lisina/sangue
Masculino
Camundongos
Osteocalcina/sangue
Estudos Retrospectivos
Inibidores da Transcriptase Reversa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Integrase Inhibitors); 0 (Protease Inhibitors); 0 (Reverse Transcriptase Inhibitors); 104982-03-8 (Osteocalcin); 94ZLA3W45F (Arginine); BJ4I2X2CQJ (pentosidine); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix246


  2 / 105 MEDLINE  
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[PMID]:28005710
[Au] Autor:De Socio GV; Ricci E; Maggi P; Parruti G; Celesia BM; Orofino G; Madeddu G; Martinelli C; Menzaghi B; Taramasso L; Bonfanti P; Pucci G; Schillaci G; CISAI study group
[Ad] Endereço:aUnit of Infectious Diseases, Department of Medicine, Azienda Ospedaliero-Universitaria di Perugia, Santa Maria Hospital, PerugiabDepartment of Infectious Diseases, Luigi Sacco Hospital, MilancUnit of Infectious Diseases, University of Bari, BaridDepartment of Infectious Diseases, Pescara Hospital, PescaraeUnit of Infectious Diseases, Garibaldi Hospital, University of Catania, CataniafDepartment of Infectious Diseases, Amedeo di Savoia Hospital, TuringDepartment of Clinical and Experimental Medicine, University of Sassari, SassarihDepartment of Infectious Diseases, Careggi Hospital, FlorenceiUnit of Infectious Diseases, Busto Arsizio Hospital, Busto ArsiziojInfectious Diseases, San Marino University Hospital, GenoakUnit of Infectious Diseases, Manzoni Hospital, LeccolDepartment of Medicine, University of Perugia and Unit of Internal Medicine, 'Santa Maria' Hospital, Terni, University of Perugia, Perugia, Italy.
[Ti] Título:Time trend in hypertension prevalence, awareness, treatment, and control in a contemporary cohort of HIV-infected patients: the HIV and Hypertension Study.
[So] Source:J Hypertens;35(2):409-416, 2017 Feb.
[Is] ISSN:1473-5598
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hypertension control is often inadequate in HIV patients. In a contemporary, nationwide cohort of Italian HIV-infected adults, we assessed time trends in hypertension prevalence, awareness, treatment, and control. We also evaluated predictors of cardiovascular events and of new-onset hypertension. METHODS: Multicenter prospective cohort study, sampling 961 consecutive HIV patients (71% men, mean age 46 ±â€Š9 years, 30% hypertensive) examined in 2010-2014 and after a median follow-up of 3.4 years. RESULTS: Among hypertensive patients, hypertension awareness (63% at baseline and 92% at follow-up), treatment (54 vs. 79%), and control (35 vs. 59%) all improved during follow-up. The incidence of new-onset hypertension was 50.1/1000 person-years (95% confidence interval, 41.2-60.3). Multivariable-adjusted predictors of hypertension were age, BMI, estimated cardiovascular risk, blood pressure, and advanced HIV clinical stage.In total, 35 new cardiovascular events were reported during follow-up (11.1/1000 person-years). In a multivariate model, baseline cardiovascular risk and hypertensive status predicted incident cardiovascular events, whereas a higher CD4 cell count had a protective role. In treated hypertensive patients, the use of integrase strand transfer inhibitors at follow-up was associated with a lower SBP (average yearly change, -3.8 ±â€Š1.6 vs. -0.9 ±â€Š0.5 mmHg in integrase strand transfer inhibitor users vs. nonusers, respectively, P = 0.02). CONCLUSION: Hypertension awareness, treatment, and control rates all improved in adult Italian HIV patients over the last few years, although hypertension remains highly prevalent (41%) in middle-aged HIV patients, and significantly impacts cardiovascular morbidity. Traditional risk factors and advanced HIV disease predict new-onset hypertension, whereas CD4 cell count favorably affects future cardiovascular events.
[Mh] Termos MeSH primário: Infecções por HIV/complicações
Conhecimentos, Atitudes e Prática em Saúde
Hipertensão/tratamento farmacológico
Hipertensão/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Pressão Sanguínea
Índice de Massa Corporal
Contagem de Linfócito CD4
Doenças Cardiovasculares/epidemiologia
Feminino
Seguimentos
Infecções por HIV/imunologia
Seres Humanos
Hipertensão/complicações
Hipertensão/fisiopatologia
Incidência
Inibidores de Integrase/uso terapêutico
Itália/epidemiologia
Masculino
Meia-Idade
Prevalência
Estudos Prospectivos
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Integrase Inhibitors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE
[do] DOI:10.1097/HJH.0000000000001150


  3 / 105 MEDLINE  
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[PMID]:27530391
[Au] Autor:Zoufaly A; Kraft C; Schmidbauer C; Puchhammer-Stoeckl E
[Ad] Endereço:Department of Medicine IV, Kaiser Franz Josef Hospital, Kundratstrasse 3, 1100, Vienna, Austria. alexander.zoufaly@wienkav.at.
[Ti] Título:Prevalence of integrase inhibitor resistance mutations in Austrian patients recently diagnosed with HIV from 2008 to 2013.
[So] Source:Infection;45(2):165-170, 2017 Apr.
[Is] ISSN:1439-0973
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Treatment guidelines often do not advocate testing for integrase inhibitor resistance associated mutations (IRAM) before initiation of first line ART given the extremely low prevalence of mutations found in older surveillance studies. We aimed to describe the prevalence of IRAM in Austrian patients recently diagnosed with HIV in the 5 years following introduction of integrase inhibitors and to analyse trends and factors associated with their detection. METHODS: Samples of antiretroviral treatment (ART) naïve patients recently diagnosed with HIV in Austria between 2008 and 2013 were analysed for the existence of IRAM and drug penalty scores were calculated to estimate response to drugs. Demographic and virological data were extracted from a database. Descriptive and comparative statistics were used. RESULTS: A total of 303 samples were analysed. 78 % were male and mean age was 38 years. Overall prevalence of IRAM was 2.3 %. Six percent had at least potentially low-level resistance to raltegravir or elvitegravir, versus 1 % for dolutegravir. One primary mutation was observed (F121Y) in a patient sample from 2012 leading to 5-10-fold reduced susceptibility to raltegravir and elvitegravir. Two patients carried the accessory mutations E138K and G140A, respectively, where both lie on the Q148 pathway. No temporal trend of IRAM prevalence was observed (p = 0.16). DISCUSSION: Primary IRAM are still rarely found despite the increasing use of INSTI in Austria, but there is a potential for reduced susceptibility to these drugs in selected patients. Routine resistance testing seems prudent to avoid the consequences including accumulation of further mutations and therapeutic failure.
[Mh] Termos MeSH primário: Farmacorresistência Viral
Infecções por HIV/virologia
Integrase de HIV/genética
Inibidores de Integrase/farmacologia
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Adulto
Áustria
Estudos Transversais
Feminino
Seres Humanos
Masculino
Meia-Idade
Prevalência
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrase Inhibitors); EC 2.7.7.- (HIV Integrase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160818
[St] Status:MEDLINE
[do] DOI:10.1007/s15010-016-0936-5


  4 / 105 MEDLINE  
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[PMID]:27091070
[Au] Autor:Wynn JE; Zhang W; Tebit DM; Gray LR; Hammarskjold ML; Rekosh D; Santos WL
[Ad] Endereço:Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, United States.
[Ti] Título:Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA.
[So] Source:Bioorg Med Chem;24(17):3947-3952, 2016 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A branched peptide containing multiple boronic acids was found to bind RRE IIB selectively and inhibit HIV-1 p24 capsid production in a dose-dependent manner. Structure-activity relationship studies revealed that branching in the peptide is crucial for the low micromolar binding towards RRE IIB, and the peptide demonstrates selectivity towards RRE IIB in the presence of tRNA. Footprinting studies suggest a binding site on the upper stem and internal loop regions of the RNA, which induces enzymatic cleavage of the internal loops of RRE IIB upon binding.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/química
Ácidos Borônicos/química
Peptídeos/química
RNA Viral/química
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/farmacologia
Ácidos Borônicos/farmacologia
Proteína do Núcleo p24 do HIV/antagonistas & inibidores
HIV-1/efeitos dos fármacos
HIV-1/genética
Células HeLa
Seres Humanos
Inibidores de Integrase/farmacologia
Lamivudina/farmacologia
Conformação de Ácido Nucleico
Biblioteca de Peptídeos
Peptídeos/farmacologia
Quinolonas/farmacologia
RNA Viral/genética
RNA Viral/metabolismo
Raltegravir Potássico/farmacologia
Elementos de Resposta
Relação Estrutura-Atividade
Replicação Viral/efeitos dos fármacos
Zidovudina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (BPBA3 peptide); 0 (Boronic Acids); 0 (HIV Core Protein p24); 0 (Integrase Inhibitors); 0 (JTK 303); 0 (Peptide Library); 0 (Peptides); 0 (Quinolones); 0 (RNA, Viral); 2T8Q726O95 (Lamivudine); 43Y000U234 (Raltegravir Potassium); 4B9XT59T7S (Zidovudine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160420
[St] Status:MEDLINE


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[PMID]:27074792
[Au] Autor:Skalweit MJ
[Ad] Endereço:Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA marion.skalweit@va.gov.
[Ti] Título:An unusual case of underlying rilpivirine resistance in an antiretroviral-naïve man with AIDS.
[So] Source:Int J STD AIDS;27(14):1346-1349, 2016 Dec.
[Is] ISSN:1758-1052
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Primary resistance mutations to second generation HIV non-nucleoside reverse transcriptase inhibitors are rare in HIV-infected persons in the US (estimated at 1.8%). We report an antiretroviral treatment (ART)-naïve patient with acquired immunodeficiency syndrome (AIDS) (CD4 cell count 20 cells/mm , viral load 8439 copies/mL), who was infected with HIV-1 sub-type B virus containing a reverse transcriptase mutation, E138A, associated with rilpivirine resistance. Subsequently, he was initiated on a single tablet ART regimen containing an integrase inhibitor and developed immune reconstitution inflammatory syndrome (IRIS), presenting as Mycobacterium avium cervical adenitis. The patient went on to develop rifamycin-induced neutropenia during treatment of his opportunistic infection but later recovered his counts, and remains well on an integrase-based HIV regimen. His case illustrates the growing importance of archived resistance mutations including the less common E138A mutation, as well as the risk and rapid occurrence of IRIS in AIDS patients initiated on integrase inhibitors.
[Mh] Termos MeSH primário: Síndrome de Imunodeficiência Adquirida/tratamento farmacológico
Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral/genética
Transcriptase Reversa do HIV/genética
HIV-1/efeitos dos fármacos
Síndrome Inflamatória da Reconstituição Imune/complicações
Rilpivirina/uso terapêutico
Tuberculose/complicações
[Mh] Termos MeSH secundário: Contagem de Linfócito CD4
Infecções por HIV/tratamento farmacológico
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico
Inibidores de Integrase/uso terapêutico
Masculino
Meia-Idade
Mutação
Inibidores da Transcriptase Reversa/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Integrase Inhibitors); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1); EC 2.7.7.49 (HIV Reverse Transcriptase); FI96A8X663 (Rilpivirine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:160415
[St] Status:MEDLINE


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[PMID]:26872388
[Au] Autor:Midde NM; Rahman MA; Rathi C; Li J; Meibohm B; Li W; Kumar S
[Ad] Endereço:Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
[Ti] Título:Effect of Ethanol on the Metabolic Characteristics of HIV-1 Integrase Inhibitor Elvitegravir and Elvitegravir/Cobicistat with CYP3A: An Analysis Using a Newly Developed LC-MS/MS Method.
[So] Source:PLoS One;11(2):e0149225, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elvitegravir (EVG), an integrase inhibitor for the treatment HIV infection, is increasingly becoming the part of first-line antiretroviral therapy (ART) regimen. EVG is mainly metabolized through cytochrome P450 (CYP) 3A4. Previously, we have shown that ethanol alters ART-CYP3A4 interactions with protease inhibitors thereby altering their metabolisms. However, as EVG is a fairly new class of drug, its kinetic characteristics and the effect of ethanol on EVG-CYPP3A4 interaction is poorly understood. In this study, we characterized EVG and cobicistat (COBI)-boosted EVG metabolism in human microsomes followed by ethanol-EVG, ethanol-COBI-EVG interaction with CYP3A. First, we developed and validated a simple, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of EVG in the human liver microsomes. The lower limit of quantification for the drug was at 0.003 µM (1.34 ng/ml). Extraction yield, matrix effects, drug stability, and calibration curves for the proposed method were validated according to the FDA guidelines. Time dependent kinetics data showed that 20mM ethanol decreases the apparent half-life of EVG degradation by ~50% compared to EVG alone. Our substrate kinetic results revealed that ethanol mildly decreases the catalytic efficiency for EVG metabolism. Inhibition studies demonstrated that EVG inhibits CYP3A4, and 20 mM ethanol causes a decrease in the IC50 of EVG. However, in the presence of COBI we were unable to determine these parameters effectively because COBI, being a strong inhibitor of CYP3A4, blocked the EVG/ethanol-CYP3A4 interactions. Docking studies predicted a shift of EVG or COBI binding to the active site of CYP3A4 in the presence of ethanol. Taken together, these results suggest that ethanol interacts with microsomal CYP3A and alters EVG-CYP3A4 interaction thereby altering EVG metabolism and inhibition of CYP3A4 by EVG. This finding has clinical significance because alcohol use is highly prevalent in HIV population, and there are no separate guidelines for these patients while they are on ART medication.
[Mh] Termos MeSH primário: Cobicistat/metabolismo
Citocromo P-450 CYP3A/metabolismo
Etanol/farmacologia
Integrase de HIV/metabolismo
Inibidores de Integrase/metabolismo
Quinolonas/metabolismo
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Calibragem
Cromatografia Líquida
Congelamento
Seres Humanos
Cinética
Microssomos Hepáticos/efeitos dos fármacos
Microssomos Hepáticos/metabolismo
Simulação de Acoplamento Molecular
Proteínas Recombinantes/metabolismo
Padrões de Referência
Reprodutibilidade dos Testes
Espectrometria de Massas por Ionização por Electrospray
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Integrase Inhibitors); 0 (JTK 303); 0 (Quinolones); 0 (Recombinant Proteins); 0 (p31 integrase protein, Human immunodeficiency virus 1); 3K9958V90M (Ethanol); EC 1.14.14.1 (Cytochrome P-450 CYP3A); EC 2.7.7.- (HIV Integrase); LW2E03M5PG (Cobicistat)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160213
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0149225


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[PMID]:26682615
[Au] Autor:Simonetti FR; Ricaboni D; Cattaneo D; Micheli V; Rusconi S; Gervasoni C
[Ad] Endereço:Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.
[Ti] Título:Relapse of Kaposi's Sarcoma and HHV-8 viremia in an HIV-infected patient switching from protease inhibitor to integrase inhibitor-based antiretroviral therapy.
[So] Source:J Clin Virol;74:75-7, 2016 Jan.
[Is] ISSN:1873-5967
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Combination antiretroviral therapy (cART) reduced the incidence of Kaposi's Sarcoma (KS), mainly mediated by the suppression of HIV replication and the recovery of the immune system. The effect of specific classes of antiretrovirals on KS remains unclear. However, both in vitro and clinical studies provided evidences that protease inhibitors (PI) can inhibit Human Herpesvirus 8 (HHV-8) replication and reduce KS risk and progression. Moreover, relapses of KS in HIV-infected patients switching from a PI to a non-nucleoside reverse transcriptase inhibitor-based cART have been reported. We describe here the case of a patient who experienced a relapse of KS and a rebound of HHV-8 viremia two months after switching from a PI to an integrase inhibitor-based cART.
[Mh] Termos MeSH primário: Antirretrovirais/administração & dosagem
Infecções por HIV/complicações
Herpesvirus Humano 8/isolamento & purificação
Inibidores de Integrase/administração & dosagem
Inibidores de Proteases/administração & dosagem
Sarcoma de Kaposi/diagnóstico
Viremia/diagnóstico
[Mh] Termos MeSH secundário: Antirretrovirais/efeitos adversos
Terapia Antirretroviral de Alta Atividade/efeitos adversos
Terapia Antirretroviral de Alta Atividade/métodos
Infecções por HIV/tratamento farmacológico
Seres Humanos
Inibidores de Integrase/efeitos adversos
Masculino
Meia-Idade
Recidiva
Sarcoma de Kaposi/virologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (Integrase Inhibitors); 0 (Protease Inhibitors)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151220
[St] Status:MEDLINE


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[PMID]:26324045
[Au] Autor:Latham CF; La J; Tinetti RN; Chalmers DK; Tachedjian G
[Ad] Endereço:Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne, VIC, 3004, Australia. cathlatham@burnet.edu.au.
[Ti] Título:Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors.
[So] Source:Curr Top Med Chem;16(10):1135-53, 2016.
[Is] ISSN:1873-4294
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Human immunodeficiency virus (HIV) remains a global health problem. While combined antiretroviral therapy has been successful in controlling the virus in patients, HIV can develop resistance to drugs used for treatment, rendering available drugs less effective and limiting treatment options. Initiatives to find novel drugs for HIV treatment are ongoing, although traditional drug design approaches often focus on known binding sites for inhibition of established drug targets like reverse transcriptase and integrase. These approaches tend towards generating more inhibitors in the same drug classes already used in the clinic. Lack of diversity in antiretroviral drug classes can result in limited treatment options, as cross-resistance can emerge to a whole drug class in patients treated with only one drug from that class. A fresh approach in the search for new HIV-1 drugs is fragment-based drug discovery (FBDD), a validated strategy for drug discovery based on using smaller libraries of low molecular weight molecules (<300 Da) screened using primarily biophysical assays. FBDD is aimed at not only finding novel drug scaffolds, but also probing the target protein to find new, often allosteric, inhibitory binding sites. Several fragment-based strategies have been successful in identifying novel inhibitory sites or scaffolds for two proven drug targets for HIV-1, reverse transcriptase and integrase. While any FBDD-generated HIV-1 drugs have yet to enter the clinic, recent FBDD initiatives against these two well-characterised HIV-1 targets have reinvigorated antiretroviral drug discovery and the search for novel classes of HIV-1 drugs.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/química
Fármacos Anti-HIV/farmacologia
Descoberta de Drogas
Integrase de HIV/metabolismo
Transcriptase Reversa do HIV/antagonistas & inibidores
Inibidores de Integrase/química
Inibidores de Integrase/farmacologia
[Mh] Termos MeSH secundário: Transcriptase Reversa do HIV/metabolismo
HIV-1/efeitos dos fármacos
HIV-1/enzimologia
Seres Humanos
Bibliotecas de Moléculas Pequenas/química
Bibliotecas de Moléculas Pequenas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Integrase Inhibitors); 0 (Small Molecule Libraries); EC 2.7.7.- (HIV Integrase); EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1); EC 2.7.7.49 (HIV Reverse Transcriptase)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150902
[St] Status:MEDLINE


  9 / 105 MEDLINE  
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[PMID]:26571377
[Au] Autor:Andreoni M; Marcotullio S; Puro V; De Carli G; Tambussi G; Nozza S; Gori A; Rusconi S; Santoro MM; Clementi M; Perno CF; d'Arminio Monforte A; Maggiolo F; Castagna A; De Luca A; Galli M; Giacomelli A; Borderi M; Guaraldi G; Calcagno A; Di Perri G; Bonora S; Mussini C; Di Biagio A; Puoti M; Bruno R; Zuccaro V; Antinori A; Cinque P; Croce D; Restelli U; Rizzardini G; Lazzarin A
[Ad] Endereço:Department of Infectious Diseases, University of Rome Tor Vergata, Rome, Italy.
[Ti] Título:An update on integrase inhibitors: new opportunities for a personalized therapy? The NEXTaim Project.
[So] Source:New Microbiol;38(4):443-90, 2015 Oct.
[Is] ISSN:1121-7138
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has turned from a fatal disease into a treatable chronic infection. The present work collects the opinions of several experts on the efficacy and safety of recently approved second generation of integrase inhibitors and, in particular, on the role of this new class of drugs in antiretroviral therapy. The availability of new therapeutic options represents an opportunity to ameliorate the efficacy of cART in controlling HIV replication also within viral reservoirs. The personalization of the treatment driven mainly by the management of comorbidities, HIV-HCV co-infections and aging, will be easier with antiretroviral drugs without drug-drug interactions and with a better toxicity and tolerability profile. Future assessment of economic impact for the introduction of new innovative drugs in the field of antiretroviral therapy will likely need some degree of adjustment of the evaluation criteria of costs and benefit which are currently based almost exclusively on morbidity and mortality.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Infecções por HIV/tratamento farmacológico
Inibidores de Integrase/uso terapêutico
Medicina de Precisão
[Mh] Termos MeSH secundário: Animais
Antirretrovirais/economia
Infecções por HIV/economia
Seres Humanos
Inibidores de Integrase/economia
Medicina de Precisão/economia
Medicina de Precisão/tendências
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (Integrase Inhibitors)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:151117
[Lr] Data última revisão:
151117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151117
[St] Status:MEDLINE


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[PMID]:26450805
[Au] Autor:D'Abbraccio M; Busto A; De Marco M; Figoni M; Maddaloni A; Abrescia N
[Ad] Endereço:Department of Immigration Diseases and HIV/AIDS, Unit for Immunodeficiencies and Infectious Diseases in Women, A.O. Dei Colli - Hospital for Infectious Diseases D. Cotugno, Naples, Italy.
[Ti] Título:Efficacy and Tolerability of Integrase Inhibitors in Antiretroviral-Naive Patients.
[So] Source:AIDS Rev;17(3):171-85, 2015 Jul-Sep.
[Is] ISSN:1698-6997
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:Integrase strand transfer inhibitors are a new class of antiretroviral agents recently licensed for the treatment of both naive and experienced HIV-infected patients. They inhibit the catalytic activity of the HIV-encoded enzyme integrase and prevent the integration of the HIV genome into the host cell genome, so slowing the propagation of the infection. Integrase strand transfer inhibitors cause a rapid drop in viral load, exhibit very low drug interactions (except elvitegravir/cobicistat), and have low pill burden and convenient dosing frequency. Drugs in this class have been compared to others in antiretroviral-naive patients with efavirenz and with protease inhibitors. Final results of the STARTMRK trial highlighted the better virologic and immunologic performance of raltegravir over efavirenz/emtricitabine/tenofovir disoproxil co-formulation. Raltegravir was also superior to atazanavir/ritonavir and darunavir/ritonavir in the ACTG 5257 study for the combined virologic/tolerability endpoint. Elvitegravir/cobicistat/emtricitabine/tenofovir was non-inferior to efavirenz/emtricitabine/tenofovir and to atazanavir/ritonavir plus emtricitabine/tenofovir in terms of confirmed virologic response in the GS-US-236-0102 and GS-US-236-0103 studies, respectively. Finally, dolutegravir showed non-inferiority compared to raltegravir in the SPRING-2 study and was superior to efavirenz and darunavir/ritonavir in the SINGLE and FLAMINGO trials, respectively. The aim of this review is to analyze the data on efficacy and safety of integrase strand transfer inhibitors in antiretroviral-naive HIV patients and discuss the strengths and weaknesses of drugs within this class.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/administração & dosagem
Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Compostos Heterocíclicos com 3 Anéis/administração & dosagem
Inibidores de Integrase/administração & dosagem
Raltegravir Potássico/administração & dosagem
Carga Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/farmacologia
Esquema de Medicação
Combinação de Medicamentos
Infecções por HIV/imunologia
Infecções por HIV/fisiopatologia
Compostos Heterocíclicos com 3 Anéis/farmacologia
Seres Humanos
Inibidores de Integrase/farmacologia
Raltegravir Potássico/farmacologia
Ensaios Clínicos Controlados Aleatórios como Assunto
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Drug Combinations); 0 (Heterocyclic Compounds, 3-Ring); 0 (Integrase Inhibitors); 43Y000U234 (Raltegravir Potassium); DKO1W9H7M1 (dolutegravir)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151009
[Lr] Data última revisão:
151009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151010
[St] Status:MEDLINE



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