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[PMID]:29390377
[Au] Autor:Trifan A; Stanciu C; Gheorghe L; Iacob S; Curescu M; Cijevschi Prelipcean C; Stefanescu G; Girleanu I; Chiriac S; Mihai C; Brisc C; Goldis A; Sporea I; Miftode E; Bataga S; Rogoveanu I; Preda C; Caruntu FA; Singeap AM
[Ad] Endereço:"Grigore T. Popa" University of Medicine and Pharmacy Iasi.
[Ti] Título:Efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with ribavirin for the treatment of HCV genotype 1b compensated cirrhosis in patients aged 70 years or older.
[So] Source:Medicine (Baltimore);96(50):e9271, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis.A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years.There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ±â€Š2.8 years (range 70-82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns).Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Hepatite C Crônica/tratamento farmacológico
Cirrose Hepática/tratamento farmacológico
Cirrose Hepática/virologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anilidas/uso terapêutico
Carbamatos/uso terapêutico
Farmacorresistência Viral
Quimioterapia Combinada
Feminino
Genótipo
Seres Humanos
Compostos Macrocíclicos/uso terapêutico
Masculino
Estudos Prospectivos
Ribavirina/uso terapêutico
Ritonavir/uso terapêutico
Sulfonamidas/uso terapêutico
Resposta Viral Sustentada
Uracila/análogos & derivados
Uracila/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Antiviral Agents); 0 (Carbamates); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 49717AWG6K (Ribavirin); 56HH86ZVCT (Uracil); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009271


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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]:29325476
[Au] Autor:Chamorro-de-Vega E; Gimenez-Manzorro A; Rodriguez-Gonzalez CG; Escudero-Vilaplana V; De Lorenzo-Pinto A; Iglesias-Peinado I; Herranz-Alonso A; Sanjurjo Saez M; GRUviC Study Group
[Ad] Endereço:a Pharmacy Department , Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria del Hospital Gregorio Marañón , Madrid , Spain.
[Ti] Título:Twelve weeks of ombitasvir/paritaprevir/r and dasabuvir without ribavirin is effective and safe in the treatment of patients with HCV genotype 1b infection and compensated cirrhosis: results from a real-world cohort study.
[So] Source:Expert Opin Drug Saf;17(3):235-241, 2018 Mar.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To explore the effectiveness and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV) for 12 weeks without ribavirin in adults with chronic HCV genotype 1b infection and compensated cirrhosis. METHODS: Observational study of a prospective cohort of adult patients with HCV genotype 1b infection and compensated cirrhosis who received 12 weeks of OBV/PTV/r and DSV without ribavirin. Effectiveness was assessed by recording the percentage of patients achieving sustained virological response at week 12 post-treatment (SVR12). Safety outcomes were based on the incidence of adverse events. RESULTS: Seventy-eight patients were included. The SVR12 rate was 96.1% (95%CI 89.2-99.2). Adverse events were recorded in 78.0% of patients. Of these, 97.7% were grade 1/2. One patient discontinued treatment prematurely owing to adverse events. Eighty-six interactions were detected in 43 patients (55.1%). Overall, 81.4% of interactions required close monitoring, alteration of drug dosage, or timing of administration. In 7.0% of cases, the interactions arose from contraindications that required the suspension of the concomitant drug. In 11.6% of cases, medicinal plants or foods were withdrawn. CONCLUSIONS: The simplified regimen of OBV/PTV/r+DSV administered for 12 weeks is effective and safe in patients with chronic HCV genotype 1b infection and compensated cirrhosis. No adverse reactions related to drug-drug interactions were recorded.
[Mh] Termos MeSH primário: Antivirais/administração & dosagem
Hepacivirus/genética
Hepatite C Crônica/tratamento farmacológico
Cirrose Hepática/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Anilidas/administração & dosagem
Anilidas/efeitos adversos
Antivirais/efeitos adversos
Carbamatos/administração & dosagem
Carbamatos/efeitos adversos
Estudos de Coortes
Interações Medicamentosas
Quimioterapia Combinada
Feminino
Genótipo
Hepatite C Crônica/virologia
Seres Humanos
Cirrose Hepática/virologia
Compostos Macrocíclicos/administração & dosagem
Compostos Macrocíclicos/efeitos adversos
Masculino
Meia-Idade
Estudos Prospectivos
Ritonavir/administração & dosagem
Ritonavir/efeitos adversos
Sulfonamidas/administração & dosagem
Sulfonamidas/efeitos adversos
Resultado do Tratamento
Uracila/administração & dosagem
Uracila/efeitos adversos
Uracila/análogos & derivados
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Antiviral Agents); 0 (Carbamates); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 56HH86ZVCT (Uracil); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2018.1424829


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[PMID]:29088262
[Au] Autor:Laurence J; Elhadad S; Robison T; Terry H; Varshney R; Woolington S; Ghafoory S; Choi ME; Ahamed J
[Ad] Endereço:Division of Hematology and Medical Oncology, Weill Cornell Medical College (WCMC), New York, New York, United States of America.
[Ti] Título:HIV protease inhibitor-induced cardiac dysfunction and fibrosis is mediated by platelet-derived TGF-ß1 and can be suppressed by exogenous carbon monoxide.
[So] Source:PLoS One;12(10):e0187185, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human immunodeficiency virus (HIV) infection is an independent risk factor for cardiovascular disease. This risk is magnified by certain antiretrovirals, particularly the protease inhibitor ritonavir, but the pathophysiology of this connection is unknown. We postulated that a major mechanism for antiretroviral-associated cardiac disease is pathologic fibrosis linked to platelet activation with release and activation of transforming growth factor (TGF)-ß1, and that these changes could be modeled in a murine system. We also sought to intervene utilizing inhaled carbon monoxide (CO) as proof-of-concept for therapeutics capable of regulating TGF-ß1 signaling and collagen autophagy. We demonstrate decreased cardiac function indices, including cardiac output, ejection fraction and stroke volume, and prominent cardiac fibrosis, in mice exposed to pharmacological doses of ritonavir. Cardiac output and fibrosis correlated with plasma TGF-ß1 levels. Mice with targeted deletion of TGF-ß1 in megakaryocytes/platelets (PF4CreTgfb1flox/flox) were partially protected from ritonavir-induced cardiac dysfunction and fibrosis. Inhalation of low dose CO (250ppm), used as a surrogate for upregulation of inducible heme oxygenase/endogenous CO pathways, suppressed ritonavir-induced cardiac fibrosis. This occurred in association with modulation of canonical (Smad2) and non-canonical (p38) TGF-ß1 signaling pathways. In addition, CO treatment suppressed the M1 pro-inflammatory subset of macrophages and increased M2c regulatory cells in the hearts of RTV-exposed animals. The effects of CO were dependent upon autophagy as CO did not mitigate ritonavir-induced fibrosis in autophagy-deficient LC3-/- mice. These results suggest that platelet-derived TGF-ß1 contributes to ritonavir-associated cardiac dysfunction and fibrosis, extending the relevance of our findings to other antiretrovirals that also activate platelets. The anti-fibrotic effects of CO are linked to alterations in TGF-ß1 signaling and autophagy, suggesting a proof-of-concept for novel interventions in HIV/antiretroviral therapy-mediated cardiovascular disease.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Monóxido de Carbono/farmacologia
Inibidores da Protease de HIV/efeitos adversos
Cardiopatias/induzido quimicamente
Miocárdio/patologia
Ritonavir/efeitos adversos
Fator de Crescimento Transformador beta1/metabolismo
[Mh] Termos MeSH secundário: Animais
Plaquetas/efeitos dos fármacos
Débito Cardíaco/efeitos dos fármacos
Ecocardiografia
Fibrose
Cardiopatias/prevenção & controle
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Volume Sistólico/efeitos dos fármacos
Fator de Crescimento Transformador beta1/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Protease Inhibitors); 0 (Transforming Growth Factor beta1); 7U1EE4V452 (Carbon Monoxide); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171101
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0187185


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[PMID]:28923796
[Au] Autor:Veilleux O; Lee TC; McDonald EG
[Ad] Endereço:Department of Medicine (Veilleux, Lee, McDonald), McGill University; Clinical Practice Assessment Unit (Lee, McDonald), McGill University Health Centre, Montréal, Que.
[Ti] Título:Rebound adrenal insufficiency after withdrawal of ritonavir in a 65-year-old man using inhaled budesonide.
[So] Source:CMAJ;189(37):E1188-E1191, 2017 09 18.
[Is] ISSN:1488-2329
[Cp] País de publicação:Canada
[La] Idioma:eng
[Mh] Termos MeSH primário: Insuficiência Adrenal/etiologia
Asma/tratamento farmacológico
Budesonida/administração & dosagem
Infecções por HIV/tratamento farmacológico
Ritonavir/uso terapêutico
Suspensão de Tratamento
[Mh] Termos MeSH secundário: Administração por Inalação
Idoso
Asma/complicações
Broncodilatadores/administração & dosagem
Infecções por HIV/complicações
Inibidores da Protease de HIV
Seres Humanos
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bronchodilator Agents); 0 (HIV Protease Inhibitors); 51333-22-3 (Budesonide); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1503/cmaj.170415


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[PMID]:28902678
[Au] Autor:Smolders EJ; Smit C; T M M de Kanter C; Dofferiiof ASM; Arends JE; Brinkman K; Rijnders B; van der Valk M; Reiss P; Burger DM
[Ad] Endereço:*Department of Pharmacy, Radboud Institute of Health Sciences (RIHS) and Radboud university medical center, Nijmegen, the Netherlands; †HIV Monitoring Foundation, Amsterdam, the Netherlands; ‡Department of Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands; §Department of Internal Disease and Infectious Diseases, Radboud university medical center, Nijmegen, the Netherlands; ‖Department of Internal Medicine and Infectious Diseases, University Medical Center, Utrecht, the Netherlands; ¶Department of Internal Medicine and Infectious Diseases, OLVG, Amsterdam, the Netherlands; #Department of Internal Medicine and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands; **Academic Medical Center, Division of Infectious Diseases, and Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, the Netherlands; and ††Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands.
[Ti] Título:Brief Report: High Need to Switch cART or Comedication With the Initiation of DAAs in Elderly HIV/HCV-Coinfected Patients.
[So] Source:J Acquir Immune Defic Syndr;76(2):193-199, 2017 Oct 01.
[Is] ISSN:1944-7884
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To describe the use of nonantiretroviral comedication and combination antiretroviral therapy (cART) in patients coinfected with HIV/hepatitis C virus (HCV) and to predict the potential for drug-drug interactions (DDIs) with direct-acting antivirals (DAAs) against HCV. METHODS: This is a retrospective, cross-sectional study, using the Dutch, nationwide ATHENA observational HIV cohort database. All patients with a known HIV/HCV coinfection on January 1, 2015, were included. Comedication and cART registered in the database were listed. The potential for DDIs between DAAs and comedication/cART were predicted using http://hep-druginteractions.org. DDIs were categorized as: (1) no clinically relevant DDI; (2) possible DDI; (3) contraindication; or (4) no information available. RESULTS: We included 777 patients of whom 488 (63%) used nonantiretroviral comedication. At risk for a category 2/3 DDI with nonantiretroviral comedications were 299 patients (38%). Most DDIs were predicted with paritaprevir/ritonavir, ombitasvir ± dasabuvir (47% of the drugs) and least with grazoprevir/elbasvir (11% of the drugs). Concerning cART, daclatasvir/sofosbuvir is the most favorable combination as no cART is contraindicated with this combination. In genotype 1/4 patients, grazoprevir/elbasvir is least favorable as 75% of the patients must alter their cART. CONCLUSIONS: This study showed that comedication use in the aging HIV/HCV population is frequent and diverse. There is a high potential for DDIs between DAAs and comedication/cART.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Antivirais/uso terapêutico
Coinfecção/tratamento farmacológico
Infecções por HIV/tratamento farmacológico
Hepatite C/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Benzofuranos/uso terapêutico
Terapia Combinada
Estudos Transversais
Interações Medicamentosas
Quimioterapia Combinada
HIV/efeitos dos fármacos
Hepacivirus/efeitos dos fármacos
Seres Humanos
Imidazóis/uso terapêutico
Meia-Idade
Quinoxalinas/uso terapêutico
Estudos Retrospectivos
Ritonavir/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(pyrrolidin-2-yl)-5-(2-(4-(5-(pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole); 0 (Anti-Retroviral Agents); 0 (Antiviral Agents); 0 (Benzofurans); 0 (Imidazoles); 0 (Quinoxalines); 8YE81R1X1J (MK-5172); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1097/QAI.0000000000001488


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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


  8 / 3702 MEDLINE  
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[PMID]:28686654
[Au] Autor:Cassim H; Otwombe K; Lazarus E; Liberty A; Gray GE; Greeff OBW; Violari A
[Ad] Endereço:Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
[Ti] Título:A retrospective case-cohort study comparing treatment outcomes in abacavir versus stavudine containing first line antiretroviral treatment regimens in children <3yrs old, at a paediatric programme based in Soweto, South Africa.
[So] Source:PLoS One;12(7):e0180645, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated. METHODS: This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013. Children on abacavir/stavudine who had initiated ART at age <3 years with a regimen including lamivudine and lopinavir/ritonavir and had at least one 6 or 12 month viral load result were eligible. All ABC cases identified were matched for age at ART initiation and gender to eligible d4T controls (1:2). Outcomes analysed at 6 and 12 months post ART initiation included virological failure, mortality, immunological failure and anthropometry. Chi-square tests compared categorical measures while Kruskal-Wallis compared continuous measures. RESULTS: We identified 57 eligible ABC cases and selected 114 matched d4T controls. Overall, 57% were females and 89% started treatment at age <1year. The median age at ART initiation was 3.11 (IQR: 1.98-6.05) months. There was no difference in the proportion of children virologically suppressed between the groups at 6 (ABC 54.5% vs. d4T 67.0%, p = 0.125) and 12 (ABC 66.7% vs. d4T 71.6%, p = 0.53) months post ART-initiation. The proportion of children with adherence levels >90% for ABC and d4T were similar too (95% in ABC vs. 86% in d4T, p = 0.10). The proportion of children who died over 12 months was 3.5% in the ABC and 7.9% in the d4T group (p = 0.27). Similarly, the anthropometric measures were comparable. CONCLUSIONS: It is reassuring that in the short term, in this group of patients, the treatment outcomes were similar.
[Mh] Termos MeSH primário: Didesoxinucleosídeos/administração & dosagem
Infecções por HIV/tratamento farmacológico
HIV/efeitos dos fármacos
Estavudina/administração & dosagem
[Mh] Termos MeSH secundário: Pré-Escolar
Combinação de Medicamentos
Feminino
HIV/patogenicidade
Infecções por HIV/epidemiologia
Infecções por HIV/patologia
Infecções por HIV/virologia
Seres Humanos
Lactente
Lamivudina/administração & dosagem
Lopinavir/administração & dosagem
Masculino
Estudos Retrospectivos
Ritonavir/administração & dosagem
África do Sul/epidemiologia
Resultado do Tratamento
Carga Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dideoxynucleosides); 0 (Drug Combinations); 0 (lopinavir-ritonavir drug combination); 2494G1JF75 (Lopinavir); 2T8Q726O95 (Lamivudine); BO9LE4QFZF (Stavudine); O3J8G9O825 (Ritonavir); WR2TIP26VS (abacavir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180645


  9 / 3702 MEDLINE  
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[PMID]:28686590
[Au] Autor:Leventer-Roberts M; Hammerman A; Brufman I; Hoshen M; Braun M; Ashur Y; Lieberman N; Balicer R
[Ad] Endereço:Clalit Research Institute, Tel Aviv, Israel.
[Ti] Título:Effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir for hepatitis C virus in clinical practice: A population-based observational study.
[So] Source:PLoS One;12(7):e0176858, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Direct acting antivirals for hepatitis C virus have shown dramatic results in clinical trials. However, their effectiveness has yet to be demonstrated within observational cohorts which lack exclusion criteria found in randomized control trials. AIM: To determine the effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir in achieving sustained virological response. METHODS: Retrospective observational cohort study of all Clalit Health Services members with hepatitis C virus genotype 1 who were dispensed dasabuvir/ombitasvir/paritaprevir/ritonavir from January 1, 2015 to-November 31, 2015. RESULTS: There were 564 participants during the study period. The average age was 61.9 years, 52.0% were male, and 61.5% were born Eastern/Central Europe or Central Asia. The prevalence of diabetes was 31.7% and 70.3% were overweight/obese. Cirrhosis was present in 41.0% of participants, of whom 52.8% had stage 4 fibrosis. Of the cohort, 416 (74.8%) had follow-up viral load testing at 10 or more weeks after the end of treatment. We report a sustained virological response of 98.8% among those tested. CONCLUSIONS: Treatment with dasabuvir/ombitasvir/paritaprevir/ritonavir demonstrated a near universal effectiveness in achieving a sustained virological response among HCV patients in a large cohort.
[Mh] Termos MeSH primário: Combinação de Medicamentos
Hepacivirus/efeitos dos fármacos
Hepatite C Crônica/tratamento farmacológico
Cirrose Hepática/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Anilidas/administração & dosagem
Carbamatos/administração & dosagem
Feminino
Genótipo
Hepacivirus/patogenicidade
Hepatite C Crônica/patologia
Hepatite C Crônica/virologia
Seres Humanos
Cirrose Hepática/patologia
Cirrose Hepática/virologia
Compostos Macrocíclicos/administração & dosagem
Masculino
Meia-Idade
Ritonavir/administração & dosagem
Sulfonamidas/administração & dosagem
Uracila/administração & dosagem
Uracila/análogos & derivados
Carga Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Carbamates); 0 (Drug Combinations); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 56HH86ZVCT (Uracil); O3J8G9O825 (Ritonavir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176858


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[PMID]:28673254
[Au] Autor:Ongubo DM; Lim R; Tweya H; Stanley CC; Tembo P; Broadhurst R; Gugsa S; Ngongondo M; Speight C; Heller T; Phiri S; Hosseinipour MC
[Ad] Endereço:Tulane University School of Public Health and Tropical Medicine, New Orleans, USA.
[Ti] Título:A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.
[So] Source:BMC Infect Dis;17(1):461, 2017 Jul 03.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. METHODS: We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. RESULTS: Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p < 0.001), although adherence by pill count was similar (62.9% vs. 60.7%, p = 0.804). The odds of virological failure were higher for adults aged 25-40 years (adjusted odds ratio (aOR) 2.5, p = 0.048), those with CD4 cell count <100 (aOR 17.5, p < 0.001), and those with normal bilirubin levels (aOR 5.4, p < 0.001); but were lower for the overweight/obese patients (aOR 0.3, p = 0.026). Poor pill count adherence (aOR 0.7, p = 0.4) and male gender (aOR 1.2, p = 0.698) were not associated with second line virological failure. CONCLUSIONS: Among patients receiving atazanavir/ritonavir-based second line antiretroviral therapy, bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Bilirrubina/análise
Biomarcadores Farmacológicos/análise
Infecções por HIV/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Sulfato de Atazanavir/uso terapêutico
Contagem de Linfócito CD4
Estudos Transversais
Feminino
Seres Humanos
Malaui
Masculino
Adesão à Medicação
Meia-Idade
Ritonavir/uso terapêutico
Falha de Tratamento
Saúde da População Urbana
Carga Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Biomarkers, Pharmacological); 4MT4VIE29P (Atazanavir Sulfate); O3J8G9O825 (Ritonavir); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2528-0



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