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1.
Clin Infect Dis ; 69(9): 1489-1497, 2019 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30601950

RESUMEN

BACKGROUND: Patients who start combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection show a smaller HIV-1 latent reservoir, less immune activation, and less viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. METHODS: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. Patients who started cART <180 days after a documented primary HIV-1 infection and had an HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; noninferiority margin 10%. RESULTS: Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group vs 32/32 (100%) in the cART group (difference, 0.00%; 95% confidence interval, -100%, 4.76%). This showed noninferiority of the dolutegravir monotherapy at the prespecified level. CONCLUSION: In this pilot study consisting of patients who initiated cART during primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was noninferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART. CLINICAL TRIALS REGISTRATION: NCT02551523.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adulto , Antirretrovirales/sangre , Antirretrovirales/líquido cefalorraquídeo , Intervalos de Confianza , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/líquido cefalorraquídeo , Compuestos Heterocíclicos con 3 Anillos/sangre , Compuestos Heterocíclicos con 3 Anillos/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , ARN Viral/genética
2.
BMC Infect Dis ; 19(1): 591, 2019 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-31286879

RESUMEN

BACKGROUND: We report a rare case of Toscana virus infection imported into Switzerland in a 23-year old man who travelled to Imperia (Italy) 10 days before onset of symptoms. Symptoms included both meningitis and as well epididymitis. This is only the fourth case of Toscana virus reported in Switzerland. CASE PRESENTATION: The patient presented with lymphocytic meningitis and scrotal pain due to epididymitis. Meningitis was initially treated with ceftriaxone. Herpes simplex, tick-borne encephalitis, enterovirus, measles, mumps, rubella and Treponema pallidum were excluded with specific polymerase chain reaction (PCR) or serology. In support of routine diagnostic PCR and serology assays, unbiased viral metagenomic sequencing was performed of cerebrospinal fluid and serum. Toscana virus infection was identified in cerebrospinal fluid and the full coding sequence could be obtained. Specific PCR in cerebrospinal fluid and blood and serology with Immunoglobulin (Ig) M and IgG against Toscana virus confirmed our diagnosis. Neurological symptoms recovered spontaneously after 5 days. CONCLUSIONS: This case of Toscana virus infection highlights the benefits of unbiased metagenomic sequencing to support routine diagnostics in rare or unexpected viral infections. With increasing travel histories of patients, physicians should be aware of imported Toscana virus as the agent for viral meningitis and meningoencephalitis.


Asunto(s)
Infecciones por Bunyaviridae , Epididimitis , Meningitis Viral , Metagenómica/métodos , Virus de Nápoles de la Fiebre de la Mosca de los Arenales , Adulto , Anticuerpos Antivirales/sangre , Infecciones por Bunyaviridae/diagnóstico , Infecciones por Bunyaviridae/inmunología , Infecciones por Bunyaviridae/virología , Epididimitis/diagnóstico , Epididimitis/inmunología , Epididimitis/virología , Humanos , Italia , Masculino , Meningitis Viral/diagnóstico , Meningitis Viral/inmunología , Meningitis Viral/virología , Técnicas de Diagnóstico Molecular , ARN Viral/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Análisis de Secuencia de ARN , Suiza , Adulto Joven
3.
Biochem J ; 409(1): 65-75, 2008 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-17824845

RESUMEN

The pH(i) (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pH(i). Sensors of pH(i) include ion transport systems which control intracellular Ca2+ gradients and link changes in pH(i) to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca(2+)-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2-S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pH(i) on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2-S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2-S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2-S100A10 might have consequences for their functions as membrane organizers and channel modulators.


Asunto(s)
Anexina A2/química , Anexina A6/química , Anexinas/metabolismo , Hipoxia , Proteínas S100/química , Apoptosis , Calcio/metabolismo , Línea Celular , Membrana Celular/metabolismo , Proliferación Celular , Humanos , Concentración de Iones de Hidrógeno , Iones , Microscopía Fluorescente/métodos , Modelos Biológicos
4.
Praxis (Bern 1994) ; 108(7): 451-458, 2019.
Artículo en Alemán | MEDLINE | ID: mdl-31136273

RESUMEN

CME: Dyslipidemia and Cardiovascular Risk in HIV Infected Patients Abstract. Dyslipidemia is a common problem in HIV-infected patients and can contribute to an elevated cardiovascular risk among this patient group. An untreated HIV infection as well as certain antiretroviral drugs can lead to an unfavorable change of the lipid profile. This article describes the diagnosis, work up and treatment of dyslipidemia in HIV-infected patients.


Asunto(s)
Enfermedades Cardiovasculares , Dislipidemias , Infecciones por VIH , Terapia Antirretroviral Altamente Activa , Enfermedades Cardiovasculares/complicaciones , Dislipidemias/complicaciones , Infecciones por VIH/complicaciones , Humanos , Factores de Riesgo
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