Background Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. Objectives We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). Methods We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. Results After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78–1.04] or hospitalization (aOR 0.93; 95% CI, 0.60–1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or hospitalization (aOR 0.51; 95% CI, 0.15–1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10–1.07) compared with TAF/FTC. Conclusions TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.
A morte súbita, responsável por cerca de 20% da mortalidade natural, continua sendo um dos maiores problemas da cardiologia. O arsenal terapêutico utilizado no seu combate inclui os medicamentos antiarrítmicos, a ressecção cirúrgica, a ablação endocárdica por cateter e o implante de dispositivos elétricos: os cardioversores-desfibriladores implantáveis.Sua utilização experimentou um enorme incremento nos últimos anos e vários megaestudos têm sido realizados para delinear a melhor opção terapêutica.Os resultados desses estudos tornam mandatória a revisão do "Consenso para Implante de Cardioversor-Desfibrilador Implantável -Deca 1995".Apesar da sua maior difusão e da aparente simplicidade de seu uso, as drogas antiarrítmicas, muitas vezes têm tido até mesmo o seu valor antiarrítmico contestado, em decorrência de seus efeitos pró-arrítmicos. No estudo CASH (Cardiac Arrest Study -Hamburg), iniciado em 1987 e concluído em 1993, que comparou o uso do desfibrilador implantável com vários fármacos, o estudo no subgrupo que utilizava propafenona foi interrompido, dada a mortalidade excessiva. Por outro lado, alguns fármacos, apesar da efetividade no controle de taquiarritmias, apresentam efeitos colaterais significativos, que motivaram a sua suspensão em 27%, 40% e 42% dos pacientes, respectivamente, dos grupos dos estudo CHF -STAD (Veterans Affairs Survival Trial of Antiarrhythmic Therapy in Congestive Heart Fai-Além do efeito pró-arrítmico, o insucesso da terapêuti-ca medicamentosa pode ocorrer devido à escolha incorreta do fármaco, à dosagem inadequada ou ao uso irregular por parte do paciente e ultimamente tem sido contestado o seu valor nos pacientes com comprometimento importante da função ventricular.Os cardioversores-desfibriladores implantáveis têm se mostrado a alternativa terapêutica mais eficiente para interromper taquicardias ventriculares sustentadas e fibrilações ventriculares, sendo responsáveis por uma redução expressiva na incidência de morte súbita, evidenciada nos estudos CASH, MADIT (Multicenter Automatic Desfibrillator Implantation Trial) e AVID (Antiarrythmicos Versus Implantable Desfibrillator). Este último, projetado para 1.200 pacientes também foi interrompido em virtude das taxas de mortalidade muito discrepantes entre seus diferentes subgrupos, o que levou o comitê dirigente a considerar anti-ética a continuidade do grupo de pacientes que recebia tratamento apenas com fármacos.No MADIT, os pacientes com infarto agudo do miocárdio prévio e disfunção ventricular (fração de ejeção menor ou igual a 35%), que apresentavam taquicardias ventriculares sustentadas ou fibrilação ventricular induzidas no estudo eletrofisiológico, foram divididos em dois grupos: um que recebeu o implante de cardioversor-desfibrilador implantável e outro, terapia antiarrítmica convencional. A discrepância da mortalidade após seguimento mé-dio de 27 meses (15% e 38% respectivamente) fez com que o Food and Drug Administration (FDA) dos Estados Unidos da América autorizasse a indicação de cardioversor-desfibrilador implantáve...
Objectives To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. Methods This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50 copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350 cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. Results We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%–4.3%), 4.7% (95% CI 2.2%–7.1%) and 7.6% (95% CI 5.4%–9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3–0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. Conclusions In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.
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