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


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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]:29329305
[Au] Autor:Lee HJ; Kim SJ; Kweon YO; Park SY; Heo J; Woo HY; Hwang JS; Chung WJ; Lee CH; Kim BS; Suh JI; Tak WY; Jang BK
[Ad] Endereço:Department of Internal Medicine, Yeungnam University College of Medicine Daegu, South Korea.
[Ti] Título:Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients.
[So] Source:PLoS One;13(1):e0190581, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METHODS: In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96. RESULTS: Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84-5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000). CONCLUSIONS: Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function. TRIAL REGISTRATION: ClinicalTrials.gov NCT01732367.
[Mh] Termos MeSH primário: Adenina/análogos & derivados
Antivirais/administração & dosagem
Hepatite B Crônica/tratamento farmacológico
Lamivudina/administração & dosagem
Organofosfonatos/administração & dosagem
Ácidos Fosforosos/administração & dosagem
[Mh] Termos MeSH secundário: Adenina/administração & dosagem
Adulto
DNA Viral/sangue
Farmacorresistência Viral
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine); 0 (Antiviral Agents); 0 (DNA, Viral); 0 (Organophosphonates); 0 (Phosphorous Acids); 2T8Q726O95 (Lamivudine); 6GQP90I798 (adefovir); JAC85A2161 (Adenine)
[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:180113
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190581


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[PMID]:28741965
[Au] Autor:Pialoux G; Marcelin AG; Cawston H; Guilmet C; Finkielsztejn L; Laurisse A; Aubin C
[Ad] Endereço:a Service des Maladies Infectieuses et Tropicales , AP-HP Hôpital Tenon , PARIS , France.
[Ti] Título:Cost-effectiveness of dolutegravir/abacavir/lamivudine in HIV-1 treatment-Naive (TN) patients in France.
[So] Source:Expert Rev Pharmacoecon Outcomes Res;18(1):83-91, 2018 Feb.
[Is] ISSN:1744-8379
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naive (TN) HIV adult patients. METHODS: The ARAMIS microsimulation Markov model, evaluates costs and effects of DTG vs. first-line ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse transcriptase inhibitors (efavirenz and rilpivirine). Efficacy and safety data were derived from phase III studies and network meta-analysis. Treatment algorithms were based on French guidelines and experts opinion. Costs included routine HIV and opportunistic infection care, and death. RESULTS: The model showed the fixed-dose combination DTG/ABC/3TC was more effective than all other recommended regimens: patients stayed longer on first-line, and lived longer and healthier. With the exception of EFV, DTG/ABC/3TC was more efficacious and less costly compared to all strategies. The cost per QALY gained (ICER) for DTG compared to EFV was €6,939. DTG/ABC/3TC was more efficacious and less costly compared to INIs and PIs in all deterministic sensitivity analyses. CONCLUSION: DTG/ABC/3TC was cost-effective in the management of HIV TN patients in France. These results are mainly explained by its lower price compared to other INIs and PIs, DTG's superior efficacy and high barrier to resistance.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/administração & dosagem
Didesoxinucleosídeos/administração & dosagem
Infecções por HIV/tratamento farmacológico
Compostos Heterocíclicos com 3 Anéis/administração & dosagem
Lamivudina/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Algoritmos
Fármacos Anti-HIV/efeitos adversos
Fármacos Anti-HIV/economia
Análise Custo-Benefício
Didesoxinucleosídeos/efeitos adversos
Didesoxinucleosídeos/economia
Combinação de Medicamentos
França
Infecções por HIV/economia
Inibidores de Integrase de HIV/administração & dosagem
Inibidores de Integrase de HIV/efeitos adversos
Inibidores de Integrase de HIV/economia
HIV-1
Compostos Heterocíclicos com 3 Anéis/efeitos adversos
Compostos Heterocíclicos com 3 Anéis/economia
Seres Humanos
Lamivudina/efeitos adversos
Lamivudina/economia
Cadeias de Markov
Guias de Prática Clínica como Assunto
Anos de Vida Ajustados por Qualidade de Vida
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Dideoxynucleosides); 0 (Drug Combinations); 0 (HIV Integrase Inhibitors); 0 (Heterocyclic Compounds, 3-Ring); 0 (abacavir, lamivudine drug combination); 2T8Q726O95 (Lamivudine); DKO1W9H7M1 (dolutegravir)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1080/14737167.2017.1359542


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[PMID]:28450288
[Au] Autor:Kermode-Scott B
[Ad] Endereço:Comox, Canada.
[Ti] Título:Mark Arnold Wainberg.
[So] Source:BMJ;357:j2026, 2017 04 27.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Infecções por HIV/terapia
Pesquisadores
[Mh] Termos MeSH secundário: Alergia e Imunologia
Fármacos Anti-HIV/farmacologia
Pesquisa Biomédica
Canadá
História do Século XX
História do Século XXI
Seres Humanos
Lamivudina/farmacologia
Masculino
Microbiologia
Pediatria
[Pt] Tipo de publicação:BIOGRAPHY; HISTORICAL ARTICLE; JOURNAL ARTICLE
[Ps] Nome de pessoa como assunto:Wainberg MA
[Nm] Nome de substância:
0 (Anti-HIV Agents); 2T8Q726O95 (Lamivudine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j2026


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[PMID]:28806922
[Au] Autor:Cerva C; Maffongelli G; Svicher V; Salpini R; Colagrossi L; Battisti A; Mariotti B; Cerretti R; Cudillo L; Sarmati L
[Ad] Endereço:Clinical Infectious Disease, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
[Ti] Título:Hepatitis B reactivation characterized by HBsAg negativity and anti-HbsAg antibodies persistence in haematopoietic stem cell transplanted patient after lamivudine withdrawal.
[So] Source:BMC Infect Dis;17(1):566, 2017 Aug 15.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: HBV reactivation is associated with high mortality rates in hematopoietic stem cell transplantation (HSCT) and prophylactic lamivudine (LMV) treatment is suggested to prevent this phenomenon. However, the duration of LMV treatment in HSCT patients is not fully defined and the time of immune recovery is considered the best parameter for a drug to be safely interrupted. In patients undergoing allogeneic HSCT, the time of immune recovery is not easy to define and may take years after transplantation and prolonged LMV treatments, which can lead to drug-resistant viral strains. CASE PRESENTATION: An anti-HBc-positive hematological patient who was undergoing prolonged immunosuppression and who experienced HBV reactivation 3 months after the suspension of a prolonged LMV prophylaxis is described. HBV-DNA matching an atypical serological profile characterized by HbsAg negativity and anti-HBs positivity was detected in the patient. The genotypic analysis of the HBV strain identified T127P, F170FL and S204R mutations of HbsAg, which can hinder HBsAg recognition in a diagnostic assay. CONCLUSIONS: HBV reactivation in the HSCT host can be sustained by HBsAg viral variants with characteristics of altered immunogenicity that cannot be detected by usual laboratory tests. This clinical case description suggests the importance of screening for serum HBV-DNA levels in the diagnosis of HBV reactivation and monitoring HBV-DNA after prophylaxis suspension, particularly in HSCT subjects who have undergone prolonged periods of LMV treatment.
[Mh] Termos MeSH primário: Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Antígenos de Superfície da Hepatite B/sangue
Vírus da Hepatite B/fisiologia
Hepatite B/prevenção & controle
Lamivudina/uso terapêutico
[Mh] Termos MeSH secundário: Antibioticoprofilaxia
Hepatite B/tratamento farmacológico
Hepatite B/etiologia
Anticorpos Anti-Hepatite B/sangue
Antígenos de Superfície da Hepatite B/imunologia
Vírus da Hepatite B/imunologia
Vírus da Hepatite B/patogenicidade
Seres Humanos
Hospedeiro Imunocomprometido
Masculino
Meia-Idade
Ativação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hepatitis B Antibodies); 0 (Hepatitis B Surface Antigens); 2T8Q726O95 (Lamivudine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2672-6


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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]:28731907
[Au] Autor:Fung J; Wong T; Chok K; Chan A; Sin SL; Cheung TT; Dai WC; Ng K; Ng K; Man K; Seto WK; Lai CL; Yuen MF; Lo CM
[Ad] Endereço:1 The Liver Transplant Center, Queen Mary Hospital, Pok Fu Lam, Hong Kong. 2 Department of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong. 3 State Key Laboratory for Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong. 4 Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong.
[Ti] Título:Oral Nucleos(t)ide Analogs Alone After Liver Transplantation in Chronic Hepatitis B With Preexisting rt204 Mutation.
[So] Source:Transplantation;101(10):2391-2398, 2017 Oct.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is currently limited data regarding the use of oral antiviral therapy alone without hepatitis B immune globulin for chronic hepatitis B patients with preexisting lamivudine (LAM) resistance (LAM-R) undergoing liver transplantation. METHODS: This is a cohort study determining the effectiveness and long-term outcome in this group of patients. RESULTS: Fifty-seven consecutive chronic hepatitis B patients with preexisting rt204 LAM-R mutations or virological load refractory to LAM undergoing liver transplantation were included, with a median follow-up of 73 months. Fifty-five (96.5%) patients received a regimen that included the use of nucleotide analogs. The cumulative rate of hepatitis B surface antigen seroclearance at 1, 5, and 10 years was 82%, 88%, and 91%, respectively. At the time of transplantation, 39 (72%) patients had detectable hepatitis B virus (HBV) DNA, with a median of 4.5 log copies/mL. The cumulative rate of HBV undetectability was 91% at 1 year, increasing to 100% by 5 years. After 1 year of liver transplantation, over 90% of the patients had undetectable HBV DNA, and from 8 years onward, 100% had undetectable HBV DNA. The overall long-term survival was excellent, with a 12-year survival of 87%. There was no HBV-related graft loss, and no retransplantation or deaths due to HBV reactivation. CONCLUSION: Oral antiviral therapy alone without hepatitis B immune globulin is highly effective in preventing HBV reactivation and graft loss from recurrent hepatitis B after liver transplantation in patients with preexisting LAM resistance HBV. The long-term outcome was excellent, with survival of 87% at 12 years after transplantation, without any mortality related to HBV reactivation.
[Mh] Termos MeSH primário: Antivirais/administração & dosagem
Farmacorresistência Viral/genética
Doença Hepática Terminal/cirurgia
Vírus da Hepatite B/efeitos dos fármacos
Hepatite B Crônica/tratamento farmacológico
Lamivudina/administração & dosagem
Transplante de Fígado
Mutação
Nucleosídeos/administração & dosagem
Nucleotídeos/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Adulto
Idoso
Antivirais/efeitos adversos
DNA Viral/genética
Esquema de Medicação
Doença Hepática Terminal/diagnóstico
Doença Hepática Terminal/mortalidade
Doença Hepática Terminal/virologia
Feminino
Genótipo
Sobrevivência de Enxerto/efeitos dos fármacos
Vírus da Hepatite B/genética
Hepatite B Crônica/diagnóstico
Hepatite B Crônica/mortalidade
Hepatite B Crônica/virologia
Seres Humanos
Estimativa de Kaplan-Meier
Transplante de Fígado/efeitos adversos
Transplante de Fígado/mortalidade
Masculino
Meia-Idade
Nucleosídeos/efeitos adversos
Nucleotídeos/efeitos adversos
Recidiva
Fatores de Risco
Fatores de Tempo
Resultado do Tratamento
Carga Viral
Ativação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (DNA, Viral); 0 (Nucleosides); 0 (Nucleotides); 2T8Q726O95 (Lamivudine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001883


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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



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