Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse ...and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.
Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from ...five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates.
There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure ...and rescue treatment options in these patients.
Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients.
Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12.
VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients.
The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).
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•In patients with VOX/VEL/SOF failure HCV GT3a infections and cirrhosis were overrepresented and HCC was present in 28% of patients•Sequencing after VOX/VEL/SOF failure showed minor changes in the NS3 and NS5A RAS pattern and no NS5B RASs were observed in comparison to baseline•Rescue treatment was conducted in 55% of patients and the main reasons were the presence of advanced liver disease and/or liver cancer•The majority of patients (68%) received G/P+SOF ± ribavirin•Rescue treatment was effective in the majority of patients with 81% SVR
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•We provide recommendations on how to use resistance data and achieve 90% sustained virological response.•If no NS5A resistance-associated substitution is found at failure, choose ...SOF+NS5A inhibitor with ribavirin.•If genotype 3 and only Y93H, choose SOF+velpatasvir+ribavirin for 24 weeks.•If both NS5A and NS3 resistance-associated substitutions, re-treat with a SOF-based 3-drug regimen+ribavirin.•Our data may be relevant for countries with limited access to new direct-acting antiviral combinations.
Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available.
GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded.
A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin.
In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited.
Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.
Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving ...cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH.
This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA.
This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH.
CRF47_BF is a circulating recombinant form (CRF) of the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. CRF47_BF represents one of 19 CRFx_BFs and has a geographic focus ...in Spain, where it was first identified in 2010. Since its discovery, CRF47_BF has expanded considerably in Spain, predominantly through heterosexual contact (∼56% of the infections). Little is known, however, about the origin and diversity of this CRF or its epidemiological correlates, as very few samples have been available so far. This study conducts a phylogenetic analysis with representatives of all CRFx_BF sequence types along with HIV-1 M Group subtypes to validate that the CRF47_BF sequences share a unique evolutionary history. The CRFx_BF sequences cluster into a single, not well supported, clade that includes their dominant parent subtypes (B and F). This clade also includes subtype D and excludes sub-subtype F2. However, the CRF47_BF sequences all share a most recent common ancestor. Further analysis of this clade couples CRF47_BF protease-reverse transcriptase sequences and epidemiological data from an additional 87 samples collected throughout Spain, as well as additional CRF47_BF database sequences from Brazil and Spain to investigate the origin and phylodynamics of CRF47_BF. The Spanish region with the highest proportion of CRF47_BF samples in the data set was the Basque Country (43.7%) with Navarre next highest at 19.5%. We include in our analysis epidemiological data on host sex, mode of transmission, time of collection, and geographic region. The phylodynamic analysis indicates that CRF47_BF originated in Brazil around 1999-2000 and spread to Spain from Brazil in 2002-2003. The virus spread rapidly throughout Spain with an increase in population size from 2011 to 2015 and leveling off more recently. Three strongly supported clusters associated with Spanish regions (Basque Country, Navarre, and Aragon), together comprising 60.8% of the Spanish samples, were identified, one of which was also associated with transmission among men who have sex with men. The expansion in Spain of CRF47_BF, together with that of other CRFs and subtype variants of South American origin, previously reported, reflects the increasing relationship between the South American and European HIV-1 epidemics.
Background
HIV–HCV coinfection produces high morbi-mortality. Direct-acting antivirals (DAAs) have shown high efficacy, although special attention should be paid to the risk of drug interactions. ...However, due to the lack of representativeness of coinfected patients in clinical trials, it is important to know real-world results.
Objective
To evaluate DAA treatment effectiveness in coinfected patients. We also analyse safety profile of DAA treatment and drug interactions between HCV and HIV therapy.
Setting
Descriptive study carried in a tertiary hospital of Spain
Method
HIV–HCV coinfected patients treated with DAAs between November 2014 and June 2016 were included.
Main outcome measure
Efficacy was measured in terms of sustained virologic response at week 12 after the end of therapy. Adverse events that led to treatment discontinuation were registered to evaluate the safety profile, and also drug interactions between DAAs and antiretroviral treatment were evaluated.
Results
Main HCV genotypes were 1a (34.9%) and 4 (24.5%). 51.9% were HCV previously treated, 54.7% had grade 4 liver fibrosis. SVR12 was reported in 90.6%. HCV treatment was well tolerated and there were no discontinuations because of adverse events. 30.2% of HIV treatments had to be modified before DAA treatment was started due to interactions, HIV suppression was not compromised.
Conclusion
DAA treatment in coinfected patients seems to be highly effective and secure. Evaluation of drug interactions must be a priority in order to maximize effectiveness and avoid toxicity.
Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving ...cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored.
The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH.
This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA.
This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH.
Los pacientes con hipertensión resistente (HR) tienen un elevado riesgo de desarrollar eventos cardiovasculares; así, las nuevas estrategias terapéuticas para el control de la presión arterial podrían ser útiles para mejorar los resultados cardiovasculares. La prevalencia de la apnea obstructiva del sueño (AOS) es muy elevada entre los pacientes con HR. Se ha demostrado que la presión positiva continua en la vía aérea (CPAP) constituye un tratamiento efectivo para reducir la presión arterial en pacientes con HR. Sin embargo, todavía no se han estudiado los efectos a largo plazo del tratamiento con CPAP sobre los resultados cardiovasculares. El principal objetivo del estudio SARAH es evaluar el impacto de la AOS y su tratamiento en los resultados cardiovasculares (morbilidad y mortalidad) en pacientes con HR.
Este es un estudio observacional prospectivo multicéntrico en el que se incluirán 1.371 pacientes con HR, a los cuales se les realizará seguimiento una vez al año durante 5 años. En el momento de la inclusión se realizará a todos los pacientes monitorización ambulatoria de la presión arterial (MAPA), así como un estudio de sueño. Se recogerán las variables sociodemográficas, clínicas y cardiovasculares tanto al inicio del estudio como durante el seguimiento. Posteriormente, los individuos con AOS serán tratados de acuerdo con la práctica clínica estándar de cada centro. Se definirán 3 grupos en función del diagnóstico de AOS y su tratamiento: sin AOS, con AOS en tratamiento, con AOS sin tratar.
Este estudio contribuirá a averiguar el impacto a largo plazo del tratamiento de la AOS en el control de la presión arterial y los resultados cardiovasculares en pacientes con HR. Asimismo, estos resultados contribuirán a mejorar el pronóstico cardiovascular de los pacientes con HR.
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