RESUMEN
Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.
Asunto(s)
Algoritmos , Epidemias , Viaje , Infección por el Virus Zika/diagnóstico , Adulto , Femenino , Humanos , Italia , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Venezuela/epidemiología , Virus Zika/genética , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/virologíaRESUMEN
Previous studies have attempted to explore the origin of the F1 subtype, but the precise origin of the Romanian and South American F1 variants remains controversial. As the F1 subtype is the most frequent non-B variant among Europeans residing in Italy, the aim of this study was to estimate its phylogeography in order to reconstruct its origin and route of dispersion. The phylogeographical analyses, which were made using the Bayesian Markov Chain Monte Carlo approach and BEAST software, revealed two significant clades: the first included all of the Romanian strains together with a few Italian and four African isolates; the second encompassed all of the South American sequences and the large majority of Italian variants. By putting the African reference sequences into two discrete groups based on specific countries, phylogeographic analysis indicated that the F1 epidemic originated in Cameroon/Democratic Republic of Congo in the early 1940s, and was exported to South America 10 years later. Subsequently, the F1 virus spread to Angola and, from there, was exported to Romania in the early 1960s. It reached Italy in the 1970s from South America and Romania. The South American and Romanian variants of F1 have different African countries of origin and different temporal spreads. The South American variant seems to be characterized by multiple introduction events, whereas the Romanian strain probably spread as a result of a single entry. Two different pathways from South America and Romania led the F1 variant to Italy in the 1970s.
Asunto(s)
Variación Genética , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Filogeografía , África/epidemiología , Europa (Continente)/epidemiología , Genotipo , VIH-1/aislamiento & purificación , Humanos , Epidemiología Molecular , América del Sur/epidemiologíaRESUMEN
Darunavir (DRV) is an HIV-1 protease inhibitor that is used together with a low boosting dose of ritonavir as part of an antiretroviral therapy (ART) regimen in treatment-experienced and naïve HIVpositive patients. In naïve and experienced patients with no DRV-mutations, DRV is licensed at the dose of 800 mg plus 100 mg of ritonavir once daily. We report our results in seven ART-experienced HIV-infected patients, in whom a reduced dose of darunavir/ritonavir (600/100 mg once daily) successfully controlled viral replication.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Quimioterapia Combinada , Infecciones por VIH/virología , Resultado del Tratamiento , Carga ViralRESUMEN
Darunavir (DRV) is an HIV-1 protease inhibitor that is used together with a low boosting dose of ritonavir as part of an antiretroviral therapy (ART) regimen in treatment-experienced and naïve HIV-positive patients. In naïve and experienced patients with no DRV-mutations, DRV is licensed at the dose of 800 mg plus 100 mg of ritonavir once daily. We report our results in seven ART-experienced HIV-infected patients, in whom a reduced dose of darunavir/ritonavir (600/100 mg once daily) successfully controlled viral replication.