Perfil de resistencias de los regímenes basados en Sofosbuvir e implicaciones en pacientes que han fallado a un AAD / Drug resistance prole of Sofosbuvir based regimens and clinical implications in whom prior DAA failed

Sofosbuvir es un antiviral de acción directa (AAD) que inhibe la acción de la polimerasa NS5B; es el AAD comercializado con mayor barrera genética, el fármaco frente al que se han descrito menor número de sustituciones asociadas a resistencia (RAS), y el que selecciona menor proporción de RAS cuando no se alcanza respuesta viral sostenida (RVS). Cuando se falla a un régimen que incluye Sofosbuvir, los pacientes se pueden rescatar con un nuevo régimen sin necesidad de intercambiarlo. Esta es la principal y más importante implicación clínica que, a nivel virológico, presenta Sofosbuvir frente al resto de AADs. Aunque hasta el momento el rescate de los pacientes que fallan, guiado por resistencias o no, ha conseguido tasas de RVS cercanas al 90%, la llegada de la nueva combinación de sofosbuvir con velpatasvir y voxilaprevir supondrá la gran revolución en el tratamiento de rescate. Esta combinación ha demostrado en ensayos clínicos tasas de RVS en rescate entre el 91-100%, independientemente de la presencia de cirrosis, en todos los genotipos, con un único comprimido al día (sin ribavirina) y tan sólo durante 12 semanas

Sofosbuvir inhibits the NS5B polymerase of HCV and it has the higher genetic barrier to resistance amongst commercially available direct acting antivirals (DAAs). Patients failing to a sofosbuvir-containing regimen can be salvaged with a new regimen that again contains this drug. This is the principal clinical implication of sofosbuvir virology. To date, retreatment of patients who have failed their first DAA regimen, resistance-guided or not, has demonstrated to achieve SVR rates that are very close to 90%. Sofosbuvir's new combination with velpatasvir and voxilaprevir in clinical trials has demonstrated SVR rates ranging 91-100% for the retreatment of DAA experienced patients, regardless of the presence of cirrhosis, for all genotypes, with only one pill a day, without ribavirine and in a 12 week regimen

Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection.

OBJECTIVE: The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens. PATIENTS AND METHODS: From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12 evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-not-detected (TND), below the lower limit of quantification (LLOQTD) and ≥LLOQ. RESULTS: A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir±ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12 in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTD and ≥LLOQ, SVR12 was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association) 0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004. CONCLUSIONS: TW4-response indicates the probability of achieving SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting.

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

[Brain lesions in patient diagnosed of meningitis]. / Lesiones cerebrales en paciente con meningitis.

INTRODUCTION: Streptococcus pneumoniae is responsible for most community acquired bacterial meningitis in adults. During the course of meningitis, the development of a new neurological focality can be a sign of an associated complication such as cerebritis. CLINICAL CASE: We report a case of pneumococcal meningitis in a 40 year old woman who reported blurred vision one week after hospital admission. Ophthalmologic exploration was normal. Brain MR images showed areas of cerebritis. CONCLUSION: Cerebritis is a rare complication of pneumococcal meningitis. We discuss the differential diagnosis and the utility of the different imaging techniques.

Lesiones cerebrales en paciente con meningitis / Brain lesions in patient diagnosed of meningitis

Introducción. Streptococcus pneumoniae es responsable de la mayoría de las meningitis adquiridas en la comunidad en los adultos. Durante el curso de una meningitis el desarrollo de una nueva focalidad neurológica puede ser el signo de una complicación asociada como la cerebritis. Caso clínico. Presentamos el caso de una meningitis neumocócica en una mujer de 40 años que refiró visión borrosa a la semana del ingreso hospitalario. La exploración oftalmológica fue normal. Las imágenes de la resonancia magnética cerebral mostraron áreas de cerebritis. Conclusión. La cerebritis es una rara complicación de la meningitis neumocócica. Se plantea el diagnóstico diferencial y la utilidad que proporcionan las diferentes técnicas de imagen

Introduction. Streptococcus pneumoniae is responsible for most community acquired bacterial meningitis in adults. During the course of meningitis, the development of a new neurological focality can be a sign of an associated complication such as cerebritis. Clinical case. We report a case of pneumococcal meningitis in a 40 year old woman who reported blurred vision one week after hospital admission. Ophthalmologic exploration was normal. Brain MR images showed areas of cerebritis. Conclusion. Cerebritis is a rare complication of penumococcal meningitis. We discuss the differential diagnosis and the utility of the different imaging techniques

[Polyarteritis nodosa as a cause of sensory motor polyneuropathy.Apropos of a case]. / Poliarteritis nodosa como causa de polineuropatía sensitivomotora. A propósito de un caso.

We present a case of nodose polyarteritis (NPA) in a 65-years-old man with clinical manifestations at the level of the peripherical nervous system (PNS) as a subacute sensorimotor polyneuropathy. We believe that this is an interesting case due to the outlined symptomatology and the first clinical signs, not as common as the multiple mononeuropathy. The diagnosis was established through biopsy of muscle-nerve, without observing aneurysms at the Divas and with negative results for the Hepatitis B markers. Response to corticoid and immunosuppressive therapy was positive.

[Dyspnea as the first clinical manifestation of amyloidosis]. / Disnea como primera manifestación clínica de amiloidosis.

We present a case of a 65-year-old woman, in whom diagnosis of primary systemic amyloidosis was established, being dyspnea the main cause of consultation. In addition, we emphasize the importance of the adequate valorization of such symptom in a patient with no precedents of cardiorespiratory pathology.