98 research outputs found
Total HCV core antigen assay: a new marker of HCV viremia and its application during treatment of chronic hepatitis C
[Abstract] The present study assesses the clinical usefulness of the hepatitis C core antigen assay for monitoring of patients being treated for chronic hepatitis C virus (HCV) infection. Eighty-six serum samples were selected at random from 16 patients and levels of HCV RNA and HCV core antigen were determined simultaneously and in parallel to compare both techniques. The data obtained were compared by Pearsonâs correlation and the coefficients calculated by Fisher transformation and by calculating the difference and standard error. A good linear correlation was observed between both techniques. Maximum correlation, with significant difference, was found between patients infected with the 1a genotype and other genotypes. In conclusion, the HCV core antigen assay is useful for the diagnosis of early infection; however, its use for determining the exact timing of viral elimination during treatment is clearly unsuitable
Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers
[Abstract] 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 (â„âF2) was defined as stiffness >â7.5âkPa, and probable cirrhosis as >â11.8âkPa. 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 6.2â±â2.3âkPa.
Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4âkPaâ
vs 5.5âkPa, Pâ<â0.001).
Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, P value): central obesity (7.1, 1.8â27.9, 0.005), elevated fasting glucose (4.3, 1.3â27.9, 0.036), reduced high-density lipoprotein cholesterol (5.2, 1.2â23.6, 0.032) and elevated triglycerides (6.2, 1.4â28.3, 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.Instituto de Salud Carlos III; CP08/00214Instituto de Salud Carlos III; PI10/0216
Liver toxicity and risk of discontinuation in HIV/hepatitis C virus-coinfected patients receiving an etravirine-containing antiretroviral regimen: influence of liver fibrosis
Short communication[Abstract] Objectives. The aim of the study was to establish the risk of liver toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving etravirine, according to the degree of liver fibrosis.
Methods. A prospective cohort study of 211 HIV-infected patients initiating an etravirine-containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) valueâ>â5-fold higher than the upper limit of normal if baseline values were normal, or 3.5-fold higher if values were altered at baseline.
Results. Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/ÎŒL, respectively; pâ=â0.03) and baseline (374 versus 498 cells/ÎŒL, respectively; pâ=â0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor (PI) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5â69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow-up time of 449.3 patient-years (median 548 days), only one patient with advanced fibrosis (50.8âkPa) had grade 3â4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; pâ=â0.39, log-rank test) or virological failure (8% versus 12%, respectively; pâ=â0.4).
Conclusions. Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis
Update on hepatitis C virus resistance to direct-acting antiviral agents
Review[Abstract] 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 (19â48%) and is associated with resistance to simeprevir. Similarly, L31M and Y93H, key resistance mutations to NS5A inhibitors, are frequently found (6â12%) 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.Instituto de Salud Carlos III; CP08/00214Instituto de Salud Carlos III; PI10/0216
Clinical experience of raltegravir-containing regimens in HIV-infected patients during rifampicin-containing treatment of tuberculosis
Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years
[Abstract] To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66âcases/year). Overall, 53.1% had a median CD4 countsâ<â350âcells/”l and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.Instituto de Salud Carlos III; CP08/00214Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; CM13/00328Instituto de Salud Carlos III; PI13/0226
Tendencia de las hospitalizaciones, reingresos y mortalidad intrahospitalaria en los pacientes infectados por VIH entre 1993-2013: impacto de la coinfecciĂłn por el virus de la hepatitis C
[Abstract] 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 (1993â2002 and 2003â2013) 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 (5â16), 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 (2003â2013), 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.[Resumen] IntroducciĂłn. Los cambios en las caracterĂsticas epidemiolĂłgicas de los pacientes con infecciĂłn por el VIH, y la introducciĂłn del tratamiento antirretroviral de alta eficacia, han modificado el perfil de las hospitalizaciones en esta poblaciĂłn. El objetivo del estudio fue evaluar las tendencias en hospitalizaciĂłn, reingreso y mortalidad en pacientes VIH, y analizar el papel de la coinfecciĂłn por el VHC.
MĂ©todos. Estudio de cohortes retrospectivo, que incluyĂł 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 anĂĄlisis 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 dĂas (5-16), y la tasa de reingreso a los 30 dĂas del 20,1%. Se observĂł un descenso significativo en el segundo periodo (2003-2013) de las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiĂĄtricos, y un incremento de aquellas relacionadas con neoplasias, enfermedad cardiovascular, gastrointestinal y enfermedades respiratorias crĂłnicas. 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 hospitalizaciĂłn disminuyĂł de manera significativa despuĂ©s 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 psiquiĂĄtricos han descendido; por el contrario, se observĂł un aumento significativo de aquellas relacionadas con neoplasias no definitorias de sida, enfermedad cardiovascular y enfermedades respiratorias crĂłnicas. La mortalidad intrahospitalaria permanece a dĂa de hoy elevada, pero a expensas fundamentalmente de enfermedades no definitorias de sida. La coinfecciĂłn VIH/VHC incrementĂł los dĂas de hospitalizaciĂłn y los reingresos durante el periodo de estudio.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/0032
Seroprevalence of HCV and HIV infections by year of birth in Spain: impact of US CDC and USPSTF recommendations for HCV and HIV testing
Instituto de Salud Carlos III; CP08/00214Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/0032
Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?
[Abstract] 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 (2004â13) 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). KaplanâMeier 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 â„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 (Pâ=â0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524â11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA 200 copies/mL [33.7% at 24 and 60 months versus <5% for other HIV-RNA values; HR 6.943 (0.728â66.261), Pâ=â0.092].
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).Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/0226
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