Integrating the control of helminths in dairy cattle: Deworming, rotational grazing and nutritional pellets with parasiticide fungi.

Thirty-two Friesian cattle under a leaders/followers four-day rotation and passing eggs of trematodes and gastrointestinal nematodes (GIN) were studied in two trials for the integrated control of these helminths over two years. In the first trial, the effect of rotational pasturing was assessed on a group of leaders (milking cows, G-L1) and followers (dried-off cows and heifers, G-F1) supplemented daily with commercial nutritional pellets. In the second trial, leaders (G-L2) and followers (G-F2) were maintained under a rotational pasturing regime; the cows received daily commercial pelleted feed and heifers pellets manufactured with a blend of parasiticide fungi (3 × 105 chlamydospores of both Mucor circinelloides and Duddingtonia flagrans/kg pellet). Deworming via closantel and albendazole was performed in cows in each trial at the beginning of their drying periods, and fourteen days later, the fecal egg-count reductions (FECR) of Calicophoron daubneyi and GIN were from 94 to 100% (average 98 %), while the percentages of reduction of cattle shedding eggs (CPCR) were from 50 to 100% (average 77 % and 82 %, respectively). The heifers were dewormed one time only, at the beginning of each trial, and the values of FECR and CPCR were 100 % against C. daubneyi and 96 % and 83 %, respectively, against GIN. Over a period of 24 months, significantly higher numbers of helminth egg-output were observed in G-L1, with the lowest numbers in G-F2. C. daubneyi egg output was reduced by 5 % (G-L1) and 42 % (G-F1) at the end of trial 1 and by 83 % (G-L2) and 100 % (G-F2) at the end of trial 2; the numbers of GIN egg-output decreased by 13 % (G-L1) and 18 % (G-F1) at the end of trial 1, and by 72 % (G-L2) and 85 % (G-F2) at the end of trial 2. No adverse effects were detected in cattle taking pellets enriched with fungal spores (G-F2). It is concluded that long-term ingestion of spores of M. circinelloides and D. flagrans provides a valuable tool to improve the effect of rotational grazing and to lessen the risk of infection by C. daubneyi and GIN in dairy cattle, and accordingly, the performance of integrated control programs.

Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals.

BACKGROUND: Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC). OBJECTIVE: To compare the incidence of liver-related events and mortality between patients aged ≥65 and <65 years. METHODS: Prospective study comparing patients aged ≥65 and <65 years treated with DAAs. The incidence of liver-related events and mortality, and HCC was compared between age groups. RESULTS: Five hundred patients (120 aged ≥65 and 380 aged <65 years) were included. The incidence of liver-related events was 2.62 per 100 patient-years (py) in older and 1.41/100 py in younger patients. All-cause mortality was 3.89 and 1.27/100 py in older and younger patients, respectively. The respective liver-related mortality rates were 1.12 and 0.31/100 py. In patients with cirrhosis (stage F4), all-cause mortality (P = 0.283) and liver-related mortality (P = 0.254) did not differ between groups. All five liver-related deaths were related to multifocal HCC. The incidence of HCC was 1.91 and 1.43 per 100 py in the older and younger groups, respectively (P = 0.747). The diagnosis of HCC was 8 months after the end of treatment. CONCLUSIONS: The incidence of liver-related events and liver-related mortality was low in older people treated with DAAs and was similar to that in younger patients. The extra mortality in people aged ≥65 years treated with DAAs seems to be secondary to non-liver-related causes. These results support the utilization of DAAs in patients aged ≥65 years.

Short article: Viral dynamics among hepatitis C virus chronic infected patients during direct-acting antiviral agents therapy: impact for monitoring and optimizing treatment duration.

OBJECTIVES: Direct-acting antiviral agents (DAAs) have provided an ultimate treatment duration of 12 weeks for most hepatitis C virus (HCV)-infected patients. The opportunity to reduce treatment duration to 6 or 8 weeks is being evaluated. Here, the HCV viral dynamics at short times during HCV therapies and its implications for monitoring and optimizing treatment duration have been assessed. PATIENTS AND METHODS: HCV chronic infected patients who began HCV therapy (March 2014 to June 2015) at a reference hospital of the Northwest of Spain were selected. HCV-RNA was quantified at different short time points during HCV therapy using Abbott RealTime HCV assay. Epidemiological, clinical, and virological data were recorded. RESULTS: Eleven HCV-infected patients were included; 90.9% had cirrhosis (>12.5 kPa) and 72.7% were treatment-experienced. HCV genotype 1b was the most prevalent (72.7%). All of the combinations were pegylated interferon-free and all included ribavirin. The median HCV-RNA (log IU/ml) at baseline was 5.8 (5.4-6.1); the decline between baseline and day 3, weeks 4, 8, and 12 was 3.2, 4.8, 5.1, and 5.6, respectively. Fewer than 50% of patients achieved undetectable viral load at weeks 4 and 8; however, all patients achieved a sustained virologic response at 12 weeks. CONCLUSION: Rapid and high HCV-RNA decline was observed among HCV-infected patients under DAA-based regimens, especially for those without cirrhosis. Despite low rates of patients with undetectable HCV-RNA at weeks 4 and 8, all achieved a sustained virologic response at 12 weeks. These findings suggest that the time points to monitor HCV-RNA during DAA therapies and the treatment duration need to be optimized.

Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients.

BACKGROUND: New direct-acting antivirals agents (DAAs) are very safe and well tolerated. OBJECTIVES: The purpose of this study is to analyse the efficacy and safety of DAAs in elderly patients, who have co-morbidities and are on chronic medications. STUDY DESIGN: All HCV-infected patients over 65 years old in clinical follow-up at two Hospitals in Spain who initiated anti-HCV therapy were included (August 2012-October 2015). RESULTS: A total of 120 HCV mono-infected patients were recorded. Mean age of patients was 72.6±7.4years. There were 53.3% women and GT1b was the most frequent (83.3%); 64.2% had cirrhosis and 42.5% were treatment experienced. Ombitasvir+Paritaprevir/r±Dasabuvir±Ribavirin (RBV) and sofosbuvir/ledipasvir±RBV were the most frequently used regimens. Weight-adjusted dosing of RBV was included in 61.7% and 43.6% of them required a dose reduction. Most of the patients (86.7%) had concomitant chronic medication and in 35.8% adjustment was necessary. Adverse events (AE) were seen in 65% of the patients; more frequent when a protease inhibitor (PI) was being used. The sustained virological response (SVR12) per ITT was 88.3%. Only 3 patients discontinued treatment and 2 patients died. CONCLUSIONS: High rates of SVR12 (88.3%) were observed among elderly patients with DAAs-based regimens. The presence of AE was frequent (65%). The majority of these patients (86.7%) had concomitant medication that required adjustment in 1/3 of them. These findings highlight the high rates of response to DAAs in the elderly HCV-population. However, special caution must be taken when using RBV and a PI.

Effect of the Filamentous Fungus Mucor circinelloides On The Development of Eggs of the Rumen Fluke Calicophoron daubneyi (Paramphistomidae).

Ruminants infected by Paramphistomidae flukes shed eggs in the feces, which pass through different stages in the environment until the infective stages (metacercariae) are reached. The activity of the soil fungus Mucor circinelloides on the development of eggs of the rumen fluke Calicophoron daubneyi was presently tested with 3 probes, i.e., in petri plates, feces, and an aqueous environment (tubes). The effect of the fungus was assessed by recording the numbers of undeveloped, nonviable, and embryonated eggs. Nonviable eggs were considered when vacuolization occurred, the inner structures were not clearly observed, the eggshell was broken, or the embryo inside was destroyed. By considering the ability of hyphae of M. circinelloides to develop in the presence of C. daubneyi eggs, attach to their surface, and penetrate and destroy the inner embryo, this ovicidal effect was classified as type 3. After a period of 50 days, the percentage of undeveloped eggs in the feces of infected cattle was 40%; furthermore, 27% of the eggs were nonviable, and 33% were embryonated (1 miracidium inside). The addition of 4 doses of M. circinelloides spores directly onto the feces resulted in 9-31% undeveloped eggs, 38-60% nonviable eggs, and 9-21% embryonated eggs, and no statistical significances were obtained among the different doses. Placing the eggs of C. daubneyi into an aqueous solution containing 107 spores of M. circinelloides/ml for 29 days resulted in 43% undeveloped eggs, 40% nonviable eggs, and 17% embryonated eggs, whereas in the controls, the percentages were 48%, 12%, and 40%, respectively. These data demonstrate the usefulness of the spores of the fungus M. circinelloides in limiting the development of the eggs of the trematode C. daubneyi.

Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV-infected patients between 1993 and 2013: Impact of hepatitis C co-infection / Tendencia de las hospitalizaciones, reingresos y mortalidad intrahospitalaria en los pacientes infectados por VIH entre 1993-2013: impacto de la coinfección por el virus de la hepatitis C

BACKGROUND: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. METHODS: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis. RESULTS: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period

INTRODUCCIÓN: Los cambios en las características epidemiológicas de los pacientes con infección por el VIH, y la introducción del tratamiento antirretroviral de alta eficacia, han modificado el perfil de las hospitalizaciones en esta población. El objetivo del estudio fue evaluar las tendencias en hospitalización, reingreso y mortalidad en pacientes VIH, y analizar el papel de la coinfección por el VHC. MÉTODOS: Estudio de cohortes retrospectivo, que incluyó todas las hospitalizaciones de pacientes VIH entre 1993-2013. El estudio fue dividido en 2 periodos (1993-2002 y 2003-2013) para ser comparados mediante un análisis transversal. RESULTADOS: Se analizaron 22.901 pacientes/años, que presentaron 6.917 hospitalizaciones que correspondieron a 1.937 pacientes (75% varones, edad media 36±11 años, 37% coinfectados VIH/VHC). La mediana de estancia hospitalaria fue de 8 días (5-16), y la tasa de reingreso a los 30 días del 20,1%. Se observó un descenso significativo en el segundo periodo (2003-2013) de las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiátricos, y un incremento de aquellas relacionadas con neoplasias, enfermedad cardiovascular, gastrointestinal y enfermedades respiratorias crónicas. La mortalidad intrahospitalaria permanece elevada (6,8% en el primer periodo vs. 6,3% en el segundo), con un aumento progresivo de las muertes por enfermedades no definitorias de sida (37,9 vs. 68,3%; p < 0,001). La tasa de hospitalización disminuyó de manera significativa después de 1996 (4,9% anual), pero este descenso fue menos acusado en los pacientes coinfectados VIH/VHC (1,7% anual). CONCLUSIONES: Las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiátricos han descendido; por el contrario, se observó un aumento significativo de aquellas relacionadas con neoplasias no definitorias de sida, enfermedad cardiovascular y enfermedades respiratorias crónicas. La mortalidad intrahospitalaria permanece a día de hoy elevada, pero a expensas fundamentalmente de enfermedades no definitorias de sida. La coinfección VIH/VHC incrementó los días de hospitalización y los reingresos durante el periodo de estudio

Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV-infected patients between 1993 and 2013: Impact of hepatitis C co-infection.

BACKGROUND: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. METHODS: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis. RESULTS: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period.

Feeding horses with industrially manufactured pellets with fungal spores to promote nematode integrated control.

The usefulness of pellets industrially manufactured with spores of parasiticide fungi as a contribution to integrated nematode control was assessed in grazing horses throughout sixteen months. Two groups of 7 Pura Raza Galega autochthonous horses (G-T and G-P) were dewormed pour-on (1mg Ivermectin/kg bw) at the beginning of the trial, and other group (G-C) remained untreated. The G-P was provided daily with commercial pellets to which was added a mixture of fungal spores during the industrial manufacturing (2×106 spores of Mucor circinelloides and same dose of Duddingtonia flagrans/kg), and G-T and G-C received pellets without spores. The efficacy of the parasiticidal strategy was assessed by estimating the reduction in the faecal egg counts (FECR) and in the number of horses shedding eggs in the faeces (PHR), and also the egg reappearance periods (ERP). Blood analyses were performed to identify the changes in the red and white cell patterns. To ascertain if horses developed an IgG humoral response against the fungi, antigenic products collected from M. circinelloides and D. flagrans were exposed to the horse sera by using an ELISA. The faecal elimination of eggs of Parascaris equorum and strongyles ceased 2 weeks after treatment in G-T and G-P, thus the values of FECR and PHR were 100%. No P. equorum-eggs were detected later, and the strongyle egg reappearance period was 28 weeks in G-P, and 8 weeks in G-T. Strongyle egg-output values remained lower than 300 eggs per gram of faeces in the G-P, whereas numbers between 330 and 772 in G-C and G-T were recorded. Normal values for the erythrocytes, haemoglobin and haematocrit in horses consuming pellets with spores were recorded, and lower than normal in the other groups. Sensitization of horses to the fungal species was disproven. It is concluded that feeding horses with pellets industrially manufactured with fungal spores represents a very useful tool to implement an integrated control of helminths affecting horses. This strategy allows a decrease in their risk of infection, aids in reducing the frequency of anthelmintic treatment.

Brief Report: European Mitochondrial Haplogroups Impact on Liver Fibrosis Progression Among HCV and HIV/HCV-Coinfected Patients From Northwest Spain.

The impact of mitochondrial DNA haplogroups on the outcome of liver fibrosis was evaluated in 362 hepatitis C virus infection (HCV)-monoinfected and HIV/HCV-coinfected patients (147 and 215, respectively) in clinical follow-up at 2 reference hospitals in the Northwest of Spain. The mitochondrial DNA haplogroup H was the most prevalent (50.3%) in this population. The cluster Others and V were recognized as risk factors for the development of liver fibrosis while haplogroup H and HCV genotype 4 confer a lower risk. This information might be useful for prioritization of HCV treatment, especially for F0-F1 patients for whom there is no urgency for treatment.

Long-term clinical experience with darunavir (2007-2015) in a large cohort of HIV-infected patients in Spain.

The clinical experience with the protease inhibitor darunavir/ritonavir (DRV/r) was retrospectively evaluated in a cohort of 173 HIV+ patients who initiated antiretroviral treatment including DRV/r (period 2007-2015). The 43.2% had a CD4 nadir ≤100 cells/mm3 , 64.1% were treatment-experienced, and 36.5% had failed to >3 lines of antiretroviral therapy. Nonetheless, the rate of virological suppression (HIV-RNA <50 copies/ml) in naïve patients was 63%, 66.7%, and 63.6% at 48, 96, and 144 weeks, respectively. The rate of virological suppression in treatment-experienced patients was 62.7%, 78.7%, and 79.1% at 48, 96, and 144 weeks, respectively. No differences were observed according to the immunovirological status neither dosage of DRV/r. Most of them (82.6%) maintained DRV/r treatment. Causes for DRV/r discontinuation were mainly gastrointestinal and cutaneous adverse events (10.5%), switch to simplification treatment strategies (3.5%) and virological failure (1.7%). These findings demonstrate the prolonged efficacy and tolerability of DRV/r even in multi-treated HIV+ patients with an unfavorable immunovirological status. J. Med. Virol. 88:2125-2131, 2016. © 2016 Wiley Periodicals, Inc.

Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

OBJECTIVES: The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA <50 copies/mL) on ART. METHODS: Newly diagnosed (2004-13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan-Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. RESULTS: A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524-11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA <20 copies/mL) [HR 3.813 (95% CI 0.675-21.535)]. Moreover, only HIV-infected patients with at least three consecutive detected, but not quantified, HIV-RNA determinations showed a higher probability of virological rebound with >200 copies/mL [33.7% at 24 and 60 months versus <5% for other HIV-RNA values; HR 6.943 (0.728-66.261), P = 0.092]. CONCLUSIONS: Blips are frequent (22.7%) among HIV-infected patients with sustained virological suppression on ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL).

Molecular characterization of HIV-1 infection in Northwest Spain (2009-2013): Investigation of the subtype F outbreak.

BACKGROUND: HIV-1 subtype B is the predominant one in European regions several, while other subtypes and recombinants are also circulating with high prevalence. A sub-epidemic of subtype F with specific characteristics and low response to treatment has been recently identified in Galicia. In this study we investigated the characteristics of the HIV-1 subtype F sub-epidemic in A Coruña and Santiago de Compostela in Northwest Spain. METHODS: 420 newly HIV-1 diagnosed patients during 2009-2013 were enrolled in this study. HIV-1 subtyping was carried out using automated subtyping tools and phylogenetic analysis. Molecular epidemiology investigation of subtypes B and F was performed by means of phylogenetic analysis using fast maximum likelihood. Phylodynamic analysis was performed using Bayesian method as implemented in BEAST v1.8. RESULTS: Subtype B found to be the predominant (61.2% and 70.4%) followed by subtype F (25.6% and 12.0%) in both areas (A Coruña and Santiago de Compostela, respectively). The latter found to mainly spread among men having sex with men (MSM). The vast majority of subtype F lineages from both areas clustered monophyletically, while subtype B sequences clustered in several tree branches. The exponential growth of subtype F sub-epidemic dated back in 2008 by means of phylodynamic analysis. Most of new infections during 2009-2013 occurred within the subtype F transmission cluster. CONCLUSIONS: Subtype F circulates at high prevalence in A Coruña and Santiago de Compostela in Northwest Spain, suggesting that the HIV-1 epidemic in this region has distinct characteristics to the rest of Spain. Subtype F has being spreading among MSM and is currently the most actively spreading network. The single cluster spread of this local sub-epidemic might provide an explanation for the distinct characteristics and the low response to antiretroviral treatment.

Seroprevalence of HCV and HIV infections by year of birth in Spain: impact of US CDC and USPSTF recommendations for HCV and HIV testing.

BACKGROUND: The US Centers for Disease Control and Prevention (CDC) recently add the advice of one-time testing of HCV infection in persons born during 1945-1965. Moreover, the US Preventive Services Task Force (USPSTF) newly recommended one-time HIV testing for persons aged 15-65. Herein, we evaluate the potential impact of these recommendations in a reference medical area of Spain. METHODS: All assays results entries for HCV and HIV serological markers ordered at a reference lab from primary care and specialized physicians between 2008 and 2012 were recorded in a medical area which covers 501,526 citizens in Northern Spain. The year of birth were also documented. RESULTS: A total of 108,159 anti-HCV-Ab results were generated during the study period. The global rate of anti-HCV-Ab+ was 7.7% (95% CI: 7.6%-7.9%), being more prevalent in men than women (8.6% vs. 4.5%). By year of birth, the highest prevalence was found in persons born between 1955 and 1970. HCV genotype 1 was the most prevalent (59.7%) followed by genotype 3 (22.7%). Regard HIV infection, among 65,279 anti-HIV results generated the prevalence of anti-HIV+ was 1.1% (95% CI: 1.0%-1.2%), being more frequent in men (2% vs 0.5%). The years of birth with highest rates of HIV infection exactly match with those for HCV infection. CONCLUSIONS: The highest rates of HCV and HIV infections are found between 1960 and 1965. Different historical and social circumstances such as the huge intravenous drug use epidemic in the eighties in Spain, might explain it. Therefore, each country needs to determine its own HCV and HIV seroprevalences by year of birth to establish the proper recommendations for the screening of both infections.

Update on hepatitis C virus resistance to direct-acting antiviral agents.

Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) infection is driven by the selection of mutations at different positions in the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance, with significant cross-resistance between compounds belonging to the same family. However, a specific mutation profile is associated with each agent or drug class and varies depending on the genotype/subtype (e.g., genotype 1b showed higher rates of sustained virological response (SVR) and a higher genetic barrier for resistance than genotype 1a). Moreover, some resistance mutations exist as natural polymorphisms in certain genotypes/subtypes at frequencies that require baseline drug resistance testing before recommending certain antivirals. For example, the polymorphism Q80K is frequently found among genotype 1a (19-48%) and is associated with resistance to simeprevir. Similarly, L31M and Y93H, key resistance mutations to NS5A inhibitors, are frequently found (6-12%) among NS5A genotype 1 sequences. In particular, the presence of these polymorphisms may be of relevance in poorly interferon-responsive patients (i.e., null responders and non-CC IL28B) under DAA-based therapies in combination with pegylated interferon-α plus ribavirin. The relevance of pre-existing resistance mutations for responses to interferon-free DAA therapies is unclear for most regimens and requires further study.

High prevalence of subtype F in newly diagnosed HIV-1 persons in northwest Spain and evidence for impaired treatment response.

HIV-1 non-B subtype variants were found in 37.8% of 296 newly diagnosed persons in northwest Spain over the past 5 years. Subtype F was the most prevalent non-B subtype (29.6%) and displayed preferential transmission among MSM. Virologic response rates to antiretroviral therapy were lower among F subtypes compared to B subtypes at weeks 24 (31% vs. 78.3%), 48 (51.7% vs. 85.2%), and 96 (61.1% vs. 94.3%) of therapy. Subtype F was independently associated with virological response at 24 weeks.

Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers.

BACKGROUND AND AIM: There are few data of fibrosis development in chronic hepatitis B (CHB) patients classified as inactive carriers. The aim of this study is to determinate the prevalence of significant fibrosis and probable cirrhosis measured by FibroScan in real inactive CHB carriers and investigate the relationship with virological, epidemiological, and metabolic factors. METHODS: Cross-sectional cohort study including CHB inactive carriers. Liver stiffness measurement was performed with transient elastography (FibroScan). Significant fibrosis (≥ F2) was defined as stiffness > 7.5 kPa, and probable cirrhosis as > 11.8 kPa. Factors associated with significant fibrosis were explored with univariate and multivariate adjusted logistic regression analyses. RESULTS: Ninety-six CHB inactive carriers were analyzed. Of them, 24 (25%) had significant fibrosis and 7 (7%) probable cirrhosis; mean stiffness was 6.2 ± 2.3 kPa. Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4 kPa vs 5.5 kPa, P < 0.001). Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, P value): central obesity (7.1, 1.8-27.9, 0.005), elevated fasting glucose (4.3, 1.3-27.9, 0.036), reduced high-density lipoprotein cholesterol (5.2, 1.2-23.6, 0.032) and elevated triglycerides (6.2, 1.4-28.3, 0.019). Factors as age, sex, transaminases, hepatitis B virus DNA or genotype were not related with liver fibrosis. The presence of metabolic syndrome has a 69% of positive predictive value and 89% of negative predictive value for significant fibrosis. CONCLUSION: Different components of metabolic syndrome are associated with fibrosis development in CHB inactive carriers. In the absence of metabolic syndrome, significant fibrosis is uncommon in this population.

Influence of HIV infection on response to tenofovir in patients with chronic hepatitis B.

BACKGROUND: HIV worsens the natural history of chronic hepatitis B virus (HBV) infection. Suppression of HBV replication slows progression of liver damage. Information about the influence of HIV on response to tenofovir in HIV/HBV-coinfected patients is scarce. METHODS: All individuals with persistent HBsAg+ at four clinics in Spain were identified. Information from the subset that initiated tenofovir therapy was examined. RESULTS: A total of 176 patients with chronic hepatitis B were evaluated, of whom 138 (78.4%) were coinfected with HIV. Prior lamivudine exposure was extensive in both groups, and nearly half of HBV viremic patients harboured drug resistance mutations. Most patients took tenofovir coformulated along with emtricitabine (Truvada). Of 101 HBV viremic patients at the time of beginning tenofovir (78 with HIV coinfection and 33 with HBV alone), a similar proportion achieved undetectable HBV-DNA at weeks 24, 48 and 96 of tenofovir therapy. Interestingly, HIV/HBV-coinfected patients with positive HBeAg showed a lower response than HBeAg-negatives. In multivariate analysis, however, baseline serum HBV-DNA was the only predictor of virological response to tenofovir. CONCLUSION: The antiviral efficacy of tenofovir is similar in HIV/HBV-coinfected and HBV-monoinfected patients, achieving undetectable HBV-DNA nearly 90% of patients at week 96 of therapy. Baseline serum HBV-DNA is the major determinant of time-trends in virological response, with no significant influence of HBeAg, drug resistance mutations nor coinfection with hepatitis C or delta viruses.

[Malignancies in HIV-infected patients: descriptive study of 129 cases between 1993 and 2010]. / Neoplasias en pacientes con infección por VIH: Estudio descriptivo de 129 casos en el período 1993-2010.

INTRODUCTION: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART). AIM: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy. METHODS: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared. RESULTS: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%. CONCLUSIONS: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.