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[PMID]:28562771
[Au] Autor:Eyer-Silva WA; Silva GARD; Ferry FRA; Pinto JFDC
[Ad] Endereço:Centro de Ciências Biológicas e da Saúde, Hospital Universitário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro, RJ, Brasil.
[Ti] Título:Facial botryomycosis-like pyoderma in an HIV-infected patient: remission after initiation of darunavir and raltegravir.
[So] Source:Rev Soc Bras Med Trop;50(2):277-279, 2017 Mar-Apr.
[Is] ISSN:1678-9849
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Botryomycosis is an uncommon, chronic, suppurative, bacterial infection that primarily affects the skin and subcutaneous tissues. It has long been associated with defects of cellular immunity. We report a 28-year-old woman who presented with a chronic, ulcerated lesion with draining sinuses in the right malar region. Predisposing factors were HIV infection with poor immunological control, alcoholism, and a previous trauma to the right cheek. Several courses of antimicrobial therapy provided only partial and temporary remission. Complete clinical remission was only achieved 5 years later when a novel antiretroviral regimen composed of darunavir and raltegravir was initiated.
[Mh] Termos MeSH primário: Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico
Botrytis/isolamento & purificação
Dermatomicoses/tratamento farmacológico
Dermatoses Faciais/tratamento farmacológico
Pioderma/tratamento farmacológico
[Mh] Termos MeSH secundário: Infecções Oportunistas Relacionadas com a AIDS/diagnóstico
Adulto
Fármacos Anti-HIV/uso terapêutico
Darunavir/uso terapêutico
Dermatomicoses/diagnóstico
Dermatoses Faciais/diagnóstico
Feminino
Seres Humanos
Pioderma/diagnóstico
Raltegravir Potássico/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS
[Nm] Nome de substância:
0 (Anti-HIV Agents); 43Y000U234 (Raltegravir Potassium); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170705
[Lr] Data última revisão:
170705
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE


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[PMID]:28427498
[Au] Autor:Yamada E; Takagi R; Tanabe Y; Fujiwara H; Hasegawa N; Kato S
[Ti] Título:Plasma and saliva concentrations of abacavir, tenofovir, darunavir, and raltegravir in HIV-1-infected patients
.
[So] Source:Int J Clin Pharmacol Ther;55(7):567-570, 2017 Jul.
[Is] ISSN:0946-1965
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We studied the relationships between plasma and saliva concentrations of antiretroviral drugs to explore whether saliva can be used for therapeutic drug monitoring (TDM). METHODS: Abacavir (ABC), tenofovir (TFV), darunavir (DRV), and raltegravir (RAL) in plasma and saliva from 30 HIV-1-infected patients were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Mean saliva-to-plasma concentration ratios were 0.623 (ABC), 0.024 (TFV), 0.065 (DRV), and 0.0135 (RAL), which agree with the plasma protein binding rates except TFV. Significant correlations were evident between saliva and plasma concentrations of ABC, DRV, and RAL. CONCLUSIONS: This study suggests that plasma concentrations of ABC, DRV, and RAL can be estimated from their saliva concentrations and that the saliva concentration of some antiretroviral drugs reflects the unbound drug concentration in plasma.
.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/sangue
Darunavir/sangue
Didesoxinucleosídeos/sangue
Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Raltegravir Potássico/sangue
Saliva/metabolismo
Tenofovir/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/farmacocinética
Cromatografia Líquida
Darunavir/administração & dosagem
Darunavir/farmacocinética
Didesoxinucleosídeos/administração & dosagem
Didesoxinucleosídeos/farmacocinética
Monitoramento de Medicamentos/métodos
Quimioterapia Combinada
Feminino
Infecções por HIV/sangue
Infecções por HIV/diagnóstico
Infecções por HIV/virologia
HIV-1/patogenicidade
Seres Humanos
Masculino
Meia-Idade
Ligação Proteica
Raltegravir Potássico/administração & dosagem
Raltegravir Potássico/farmacocinética
Espectrometria de Massas em Tandem
Tenofovir/administração & dosagem
Tenofovir/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Dideoxynucleosides); 43Y000U234 (Raltegravir Potassium); 99YXE507IL (Tenofovir); WR2TIP26VS (abacavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.5414/CP202789


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[PMID]:28403052
[Au] Autor:Lazarus E; Nicol S; Frigati L; Penazzato M; Cotton MF; Centeno-Tablante E; Violari A; Nicol L
[Ad] Endereço:From the *Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; †FAMCRU, Children's' Infectious Diseases Clinical Research Unit, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa; ‡World Health Organization, HIV Department, Treatment and Care Unit, Geneva, Switzerland; and §Centre for Evidence-based Health Care, Department of Interdisciplinary Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
[Ti] Título:Second- and Third-line Antiretroviral Therapy for Children and Adolescents: A Scoping Review.
[So] Source:Pediatr Infect Dis J;36(5):492-499, 2017 May.
[Is] ISSN:1532-0987
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov. RESULTS: The search retrieved 1982 records. Eighteen studies provided efficacy data: 1 randomized controlled trial, 7 phase II trials, 5 prospective and 5 retrospective cohorts. Five studies evaluated regimens in children failing first-line ART, 4 in children with multidrug resistance and 9 in children with variable treatment experience. Only 10/18 studies reported week 48 or month 12 outcomes. The overall proportion of children with virologic suppression defined by study at week 48 was 61.8%. Although the randomized controlled trial had low risk of bias, outcomes were similar between groups because of highly active optimized background regimens. All phase II and prospective studies were judged to have moderate to high risk of bias. No study compared currently recommended lopinavir-based second-line regimens for nonnucleoside reverse transcriptase inhibitor failures to other non-nonnucleoside reverse transcriptase inhibitor regimens head-to-head. CONCLUSIONS: We found no evidence comparing current World Health Organization-recommended second- and third-line ART regimens with regimens including drugs of interest: raltegravir, darunavir, etravirine and atazanavir. Randomized controlled trials or prospective cohort studies with comparator arms, and bridging studies, ideally conducted in resource-limited settings, are required to guide future recommendations.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Terapia Antirretroviral de Alta Atividade
Infecções por HIV/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Sulfato de Atazanavir/uso terapêutico
Criança
Pré-Escolar
Ensaios Clínicos Fase II como Assunto
Estudos de Coortes
Darunavir/uso terapêutico
Esquema de Medicação
Feminino
Infecções por HIV/virologia
Seres Humanos
Masculino
Guias de Prática Clínica como Assunto
Piridazinas/uso terapêutico
Raltegravir Potássico/uso terapêutico
Carga Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Pyridazines); 0C50HW4FO1 (etravirine); 43Y000U234 (Raltegravir Potassium); 4MT4VIE29P (Atazanavir Sulfate); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1097/INF.0000000000001481


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[PMID]:28399819
[Au] Autor:Antoniou T; Szadkowski L; Walmsley S; Cooper C; Burchell AN; Bayoumi AM; Montaner JS; Loutfy M; Klein MB; Machouf N; Tsoukas C; Wong A; Hogg RS; Raboud J; Canadian Observational Cohort (CANOC) collaboration
[Ad] Endereço:Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. tantoniou@smh.ca.
[Ti] Título:Comparison of atazanavir/ritonavir and darunavir/ritonavir based antiretroviral therapy for antiretroviral naïve patients.
[So] Source:BMC Infect Dis;17(1):266, 2017 Apr 11.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking. METHODS: We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason). Additional endpoints included virologic failure, discontinuation due to virologic failure, discontinuation for other reasons, and virologic suppression. RESULTS: We studied 222 patients treated with darunavir/ritonavir and 1791 patients treated with atazanavir/ritonavir. Following multivariable adjustment, there was no difference between darunavir/ritonavir and atazanavir-ritonavir in the risk of regimen failure (adjusted hazard ratio 0.76, 95% CI 0.56 to 1.03) Darunavir/ritonavir-treated patients were at lower risk of virologic failure relative to atazanavir/ritonavir treated patients (aHR 0.50, 95% CI 0.28 to 0.91), findings driven largely by high rates of virologic failure among atazanavir/ritonavir-treated patients in the province of British Columbia. Of 108 discontinuations due to virologic failure, all occurred in patients starting atazanavir/ritonavir. There was no difference between regimens in time to discontinuation for reasons other than virologic failure (aHR 0.93; 95% CI 0.65 to 1.33) or virologic suppression (aHR 0.99, 95% CI 0.82 to 1.21). CONCLUSIONS: The risk of regimen failure was similar between patients treated with darunavir/ritonavir and atazanavir/ritonavir. Although darunavir/ritonavir was associated with a lower risk of virologic failure relative to atazanavir/ritonavir, this difference varied substantially by Canadian province and likely reflects regional variation in prescribing practices and patient characteristics.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Sulfato de Atazanavir/uso terapêutico
Darunavir/uso terapêutico
Infecções por HIV/tratamento farmacológico
Ritonavir/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Fármacos Anti-HIV/administração & dosagem
Sulfato de Atazanavir/administração & dosagem
Colúmbia Britânica
Canadá
Estudos de Coortes
Darunavir/administração & dosagem
Quimioterapia Combinada
Feminino
HIV-1
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Ritonavir/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 4MT4VIE29P (Atazanavir Sulfate); O3J8G9O825 (Ritonavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2379-8


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[PMID]:28361290
[Au] Autor:Menshawy A; Ismail A; Abushouk AI; Ahmed H; Menshawy E; Elmaraezy A; Gadelkarim M; Abdel-Maboud M; Attia A; Negida A
[Ad] Endereço:Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
[Ti] Título:Efficacy and safety of atazanavir/ritonavir-based antiretroviral therapy for HIV-1 infected subjects: a systematic review and meta-analysis.
[So] Source:Arch Virol;162(8):2181-2190, 2017 Aug.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA <50 copies/ml (RR 1.09, 95% CI [1.01, 1.17]). The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol, triglycerides, or high-density lipoprotein at 24, 48, and 96 weeks. Moreover, no significant difference was found between the two regimens (ATZ/r and DRV/r) in terms of change in visceral (SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Sulfato de Atazanavir/uso terapêutico
Infecções por HIV/tratamento farmacológico
Ritonavir/uso terapêutico
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/efeitos adversos
Terapia Antirretroviral de Alta Atividade/métodos
Sulfato de Atazanavir/efeitos adversos
Contagem de Linfócito CD4
Darunavir/efeitos adversos
Darunavir/uso terapêutico
HIV-1/efeitos dos fármacos
Seres Humanos
Lopinavir/efeitos adversos
Lopinavir/uso terapêutico
RNA Viral/sangue
Ensaios Clínicos Controlados Aleatórios como Assunto
Ritonavir/efeitos adversos
Resultado do Tratamento
Carga Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (RNA, Viral); 2494G1JF75 (Lopinavir); 4MT4VIE29P (Atazanavir Sulfate); O3J8G9O825 (Ritonavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170802
[Lr] Data última revisão:
170802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3346-9


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[PMID]:28333285
[Au] Autor:Calcagno A; Pagani N; Ariaudo A; Arduino G; Carcieri C; D'Avolio A; Marinaro L; Tettoni MC; Trentini L; Di Perri G; Bonora S
[Ad] Endereço:Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
[Ti] Título:Therapeutic drug monitoring of boosted PIs in HIV-positive patients: undetectable plasma concentrations and risk of virological failure.
[So] Source:J Antimicrob Chemother;72(6):1741-1744, 2017 Jun 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure. Methods: A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards. Results: The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P < 0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P  =   0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P < 0.001), genotypic susceptibility score ≤2 ( P = 0.001), lower nadir CD4 cell count ( P = 0.003) and not being in the adherent group ( P = 0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks. Conclusions: The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions.
[Mh] Termos MeSH primário: Monitoramento de Medicamentos
Infecções por HIV/tratamento farmacológico
Inibidores da Protease de HIV/sangue
Ritonavir/sangue
Carga Viral
[Mh] Termos MeSH secundário: Adulto
Sulfato de Atazanavir/sangue
Sulfato de Atazanavir/uso terapêutico
Darunavir/sangue
Darunavir/uso terapêutico
Quimioterapia Combinada
Feminino
Seguimentos
Infecções por HIV/virologia
Inibidores da Protease de HIV/uso terapêutico
HIV-1/isolamento & purificação
Seres Humanos
Lopinavir/sangue
Lopinavir/uso terapêutico
Masculino
Adesão à Medicação
Meia-Idade
RNA Viral/sangue
Sistema de Registros
Análise de Regressão
Estudos Retrospectivos
Ritonavir/uso terapêutico
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Protease Inhibitors); 0 (RNA, Viral); 2494G1JF75 (Lopinavir); 4MT4VIE29P (Atazanavir Sulfate); O3J8G9O825 (Ritonavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkx052


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[PMID]:28329334
[Au] Autor:Wyles D; Saag M; Viani RM; Lalezari J; Adeyemi O; Bhatti L; Khatri A; King JR; Hu YB; Trinh R; Shulman NS; Ruane P
[Ad] Endereço:University of Colorado School of Medicine, Denver, USA.
[Ti] Título:TURQUOISE-I Part 1b: Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin for Hepatitis C Virus Infection in HIV-1 Coinfected Patients on Darunavir.
[So] Source:J Infect Dis;215(4):599-605, 2017 02 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART). Methods: Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks. Results: Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment. Conclusions: HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Darunavir/uso terapêutico
Hepatite C/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Anilidas/uso terapêutico
Índice de Massa Corporal
Contagem de Linfócito CD4
Carbamatos/uso terapêutico
Coinfecção/tratamento farmacológico
Relação Dose-Resposta a Droga
Quimioterapia Combinada
Feminino
HIV-1/efeitos dos fármacos
HIV-1/isolamento & purificação
Hepacivirus/efeitos dos fármacos
Hepacivirus/isolamento & purificação
Seres Humanos
Compostos Macrocíclicos/uso terapêutico
Masculino
Meia-Idade
Ribavirina/uso terapêutico
Ritonavir/uso terapêutico
Sulfonamidas/uso terapêutico
Uracila/análogos & derivados
Uracila/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Anti-Retroviral Agents); 0 (Carbamates); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 49717AWG6K (Ribavirin); 56HH86ZVCT (Uracil); O3J8G9O825 (Ritonavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170715
[Lr] Data última revisão:
170715
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jiw597


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[PMID]:28192453
[Au] Autor:Gianotti N; Cozzi-Lepri A; Antinori A; Castagna A; De Luca A; Celesia BM; Galli M; Mussini C; Pinnetti C; Spagnuolo V; d'Arminio Monforte A; Ceccherini-Silberstein F; Andreoni M; Icona Foundation Study and mono-PI/r database Study Cohorts
[Ad] Endereço:San Raffaele Hospital, Milano, Italy.
[Ti] Título:Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients.
[So] Source:PLoS One;12(2):e0171611, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). DESIGN: A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. METHODS: VL was assessed in each center according to local procedures. Residual viremia was defined by any HIV-RNA value detectable below 50 copies/mL by a Real-Time PCR method. Standard survival analysis was used to estimate the rate of TF (defined by virological failure or interruption of monotherapy or reintroduction of combination therapy). A multivariable Cox regression analysis with automatic stepwise procedures was used to identify factors independently associated with TF among nadir and baseline CD4+ counts, residual viremia, time spent with <50 HIV-RNA copies/mL before switch, history of virological failure, HCV co-infection, being on a PI/r and hemoglobin concentrations at baseline. RESULTS: Six hundred ninety patients fulfilled the inclusion criteria and were included in this analysis. Their median follow-up was 20 (10-37) months. By month 36, TF occurred in 176 (30.2%; 95% CI:25.9-34.5) patients. Only CD4+ nadir counts (adjusted hazard ratio [aHR] = 2.03 [95% CI: 1.35, 3.07] for counts ≤100 vs. >100 cells/µL) and residual viremia (aHR = 1.48 [95% CI: 1.01-2.17] vs. undetectable VL) were independently associated to TF. CONCLUSIONS: Residual viremia and nadir CD4+ counts <100 cells/µL should be regarded as the main factors to be taken into account before considering switching to a PI/r-MT.
[Mh] Termos MeSH primário: Darunavir/uso terapêutico
Infecções por HIV/tratamento farmacológico
HIV/efeitos dos fármacos
Lopinavir/uso terapêutico
Ritonavir/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Terapia Antirretroviral de Alta Atividade/métodos
Contagem de Linfócito CD4
Estudos de Coortes
Quimioterapia Combinada
Feminino
HIV/genética
Infecções por HIV/virologia
Inibidores da Protease de HIV/uso terapêutico
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Avaliação de Resultados (Cuidados de Saúde)/métodos
Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos
Modelos de Riscos Proporcionais
RNA Viral/genética
Carga Viral
Viremia/sangue
Viremia/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (HIV Protease Inhibitors); 0 (RNA, Viral); 2494G1JF75 (Lopinavir); O3J8G9O825 (Ritonavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171611


  9 / 688 MEDLINE  
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[PMID]:28182610
[Au] Autor:Khoo S; Peytavin G; Burger D; Hill A; Brown K; Moecklinghoff C; La Porte C; Hadacek MB
[Ad] Endereço:Institute of Translational Medicine, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK.
[Ti] Título:Pharmacokinetics and Safety of Darunavir/Ritonavir in HIV-Infected Pregnant Women.
[So] Source:AIDS Rev;19(1):16-23, 2017 Jan-Mar.
[Is] ISSN:1698-6997
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:The dosage of darunavir/ritonavir is 800/100 mg once daily for treatment-naive patients or treatment-experienced patients with no prior darunavir resistance associated mutations, and 600/100 mg twice daily for treatment-experienced patients with one or more darunavir resistance associated mutations. Results from the five available pharmacokinetic studies show reductions in total darunavir plasma concentrations of between 20-50% during the third trimester of pregnancy. The unbound darunavir concentrations have been measured only in subsets of patients in two of the five pharmacokinetic studies. The unbound concentrations were 11% higher during pregnancy in one study of the 600/100 mg twice-daily dosage, and 13-38% lower during pregnancy for the 800/100 mg once-daily dosage. Ratios of darunavir concentration in cord blood compared to maternal plasma are in the range of 0.11-0.18, suggesting that darunavir does not have high trans-placental penetration. Despite the decrease in exposure, the darunavir/ritonavir 800/100 mg once-daily regimen in HIV-positive pregnant women in combination with background antiretroviral therapy has been effective in preventing mother-to-child transmission in the studies included in this review. Among the 137 infants born across the five studies, there was one case of mother-to-child transmission, which was in a mother taking the 600/100 mg twice-daily dose but who had documented poor adherence to treatment.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacocinética
Darunavir/farmacocinética
Infecções por HIV/tratamento farmacológico
Complicações Infecciosas na Gravidez/tratamento farmacológico
Ritonavir/farmacocinética
[Mh] Termos MeSH secundário: Anormalidades Induzidas por Medicamentos/etiologia
Animais
Darunavir/administração & dosagem
Darunavir/efeitos adversos
Quimioterapia Combinada
Feminino
Seres Humanos
Placenta/metabolismo
Gravidez
Ritonavir/administração & dosagem
Ritonavir/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); O3J8G9O825 (Ritonavir); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE


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[PMID]:27999051
[Au] Autor:Gutierrez-Valencia A; Benmarzouk-Hidalgo OJ; Llaves S; Fernandez-Magdaleno T; Espinosa N; Viciana P; Lopez-Cortes LF
[Ti] Título:Pharmacokinetic interactions between cobicistat-boosted elvitegravir and darunavir in HIV-infected patients.
[So] Source:J Antimicrob Chemother;72(3):816-819, 2017 Mar 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: To evaluate if there are significant drug-drug interactions between cobicistat-boosted elvitegravir and 800 mg darunavir once daily taken simultaneously, as has been suggested previously. Methods: The study population consisted of three groups of unselected volunteers taking a regimen of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (150, 150, 200 and 300 mg, respectively) co-formulated in a single tablet plus 800 mg darunavir (group A); only co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (group B); and cobicistat-boosted darunavir (800 mg darunavir + 150 mg cobicistat) plus two nucleos(t)ide analogues (group C). Elvitegravir, cobicistat and darunavir concentrations at the end of the dosing interval ( C 24 ) were quantified using a validated LC with tandem MS method. Results: A total of 170 samples were obtained from 24, 32 and 32 patients in groups A, B and C, respectively. In group A, the elvitegravir C 24 were similar to those in group B (233.67 versus 250.39 ng/mL) ( P = 0.406) and the darunavir C 24 were similar to those in group C (1293.54 versus 1319.34 ng/mL) ( P = 0.908). The cobicistat C 24 were comparable in groups A and B (20.2 versus 20.9 ng/mL) and slightly higher in group C (27.7 ng/mL) ( P = 0.059). Conclusions: The results provide evidence of similar elvitegravir and darunavir C 24 concentrations when these drugs are co-administered as co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate plus 800 mg darunavir or dosed separately.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacocinética
Cobicistat/administração & dosagem
Darunavir/farmacocinética
Infecções por HIV/tratamento farmacológico
Quinolonas/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/uso terapêutico
Cobicistat/uso terapêutico
Darunavir/administração & dosagem
Darunavir/uso terapêutico
Combinação de Medicamentos
Interações Medicamentosas
Feminino
Infecções por HIV/virologia
HIV-1/efeitos dos fármacos
Seres Humanos
Masculino
Meia-Idade
Quinolonas/administração & dosagem
Quinolonas/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Drug Combinations); 0 (JTK 303); 0 (Quinolones); LW2E03M5PG (Cobicistat); YO603Y8113 (Darunavir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw487



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