209 research outputs found
Auswirkungen von Lopinavir-haltiger hoch-aktiver antiretroviraler Therapie (HAART) auf den Kohlehydrat- und Lipidstoffwechsel bei HIV-Infizierten
Seit der EinfĂŒhrung hochaktiver antiretroviraler Therapieschemata ist die MorbiditĂ€t und MortalitĂ€t HIV-Infizierter erheblich gesunken. Die Medikamentenkombinationen, und insb. die Proteaseinhibitoren, können jedoch zu StoffwechselverĂ€nderungen des Kohlehydrat und Lipidstoffwechsels fĂŒhren, die langfristig zu erheblichen Nebenwirkungen wie z.B. Myokardinfarkten fĂŒhren können. Ziel der Arbeit war es, die Auswirkungen auf den Kohlehydrat- und Lipidstoffwechsel eines der am hĂ€ufigsten verordneten Proteaseinhibitoren (Lopinavir) im Vergleich zu anderen Therapieschemata zu untersuchen. Patienten wurden 3 Gruppen zugeornet: 1. Therapie mit Lopinavir, 2. Therapie ohne Proteasehemmer, 3. keine antiretrovirale Therapie. Methodik: Die Patienten wurden einmalig zur DurchfĂŒhrung eines oralen Glukosetoleranztests, NĂŒchterninsulinbestimmung, eines Lipidprofils und mĂŒndlicher Befragung bzgl kardiovaskulĂ€rer Risikofaktoren einbestellt. Ergebnisse: Insgesamt 61 Patienten (22 Gruppe 1, 17 Gruppe 2, 22 Gruppe 3) wurden untersucht. Die Patienten waren ĂŒberwiegend mĂ€nnlich, der HIV-Ăbertragungsweg war ĂŒbverwiegend homosexueller Geschlechtsverkehr. Keine signifikanten Unterschiede fanden sich beim Vergleich von kardiovaskuĂ€ren Risikofaktoren. Patienten, die eine antiretrovirale Therapie erhielt hatten signifikant erhöhte NĂŒchternblutzuckerwerte. Ebenfalls war eine Lopinavir-haltige HAART mit erhöhten Triglyceriden und VLDL-Cholesterol assoziiert. Obwohl derzeit keine Alternative zur antiretroviralen Therapie bei HIV-Infizierten besteht, kann diese zu StoffwechselverĂ€nderungen fĂŒhren, die langfristig mit erheblich Nebenwirkungen verbunden sein können.</p
Acute hepatitis C in persons infected with the human immunodeficiency virus (HIV): the 'real-life setting' proves the concept
Concordance in a World without a Gold Standard: A New Non-Invasive Methodology for Improving Accuracy of Fibrosis Markers
BACKGROUND: Assessing liver fibrosis is traditionally performed by biopsy, an imperfect gold standard. Non-invasive techniques, liver stiffness measurements (LSM) and biomarkers [FibroTest(R) (FT)], are widely used in countries where they are available. The aim was to identify factors associated with LSM accuracy using FT as a non-invasive endpoint and vice versa. METHODS: The proof of concept was taken using the manufacturers recommendations for excluding patients at high risk of false negative/positive. The hypothesis was that the concordance between LSM and FT, would be improved by excluding high-risk patients. Thereafter, the impact of potential variability factors was assessed by the same methods. Liver biopsy and independent endpoints were used to validate the results. RESULTS: Applying manufacturers' recommendations in 2,004 patients increased the strength of concordance between LSM and FT (P<0.00001). Among the 1,338 patients satisfying recommendations, the methodology identified a significant LSM operator effect (P = 0.001) and the following variability factors (all P<0.01), related to LSM: male gender, older age, and NAFLD as a cause of liver disease. Biopsy confirmed in 391 patients these results. CONCLUSION: This study has validated the concept of using the strength of concordance between non-invasive estimates of liver fibrosis for the identification of factors associated with variability and precautions of use
New drugs for non-alcoholic steatohepatitis and HIV infection: great expectations with a great absent?
In recent years, there has been an increasing number of clinical trials for the treatment of nonâalcoholic steatohepatitis (NASH). People living with HIV (PLWH) are commonly excluded from these studies, usually due to concerns over drugâdrug interactions (DDI) associated with antiretroviral therapy (ART). The Steatohepatitis in HIV Emerging Research (SHIVER) Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between HIV and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of DDI between ART and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGLâ3196), which are currently in phase III trials for the treatment of NASH, are reviewed. Finally, a model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a subâpopulation within studies
HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe
BACKGROUND & AIMS: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. METHODS: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014. RESULTS: Of 606 individuals who cleared HCV spontaneously or were successfully treated, 149 (24.6%) presented with a subsequent HCV reinfection. Thirty out of 70 (43%) who cleared again or were successfully treated, presented with a second reinfection, 5 with a third, and one with a fourth reinfection. The reinfection incidence was 7.3/100 person-years (95% CI 6.2-8.6). We found a trend for lower incidence among individuals who had spontaneously cleared their incident infection than among individuals who were treated (Hazard ratio 0.62, 95% CI 0.38-1.02, p=0.06). Spontaneous clearance of reinfection was associated with ALT levels >1000IU/ml and spontaneous clearance of a prior infection. CONCLUSIONS: HCV reinfection is an issue of major concern in HIV-positive MSM. Prevention strategies are needed for high risk groups to reduce morbidity and treatment costs. HIV-positive MSM with a prior HCV infection should be tested every 3 to 6months for reinfection. Those who had achieved a reinfection should be tested every 3months. LAY SUMMARY: We evaluated the occurrence of HCV reinfection in HIV-positive men who have sex with men. We found an alarming incidence of 7.3/100 person-years. Prevention measures need to address this specific subgroup of patients at high risk for HCV
Phylogenetic analysis of an epidemic outbreak of acute hepatitis C in HIV-infected patients by ultra-deep pyrosequencing
Background: The incidence of acute hepatitis C (AHC) among HIV-infected men who have sex with men (MSM) has increased significantly in the last 10 years. Several studies point to a social and sexual network of HIV-positive MSM that extends internationally. Objectives: The aim of our study was to investigate the dynamics of HCV transmission in an outbreak of AHC in HIV-infected MSM in Barcelona by ultra-deep pyrosequencing. Study design: Between 2008 and 2013, 113 cases of AHC in HIV-infected MSM were diagnosed in the Infectious Diseases Unit, Hospital ClĂnic, Barcelona. Massive sequencing was performed using the Roche 454 GS Junior platform. To define possible transmission networks, maximum likelihood phylogenetic trees were constructed, and levels of genetic diversity within and among patients were compared. Results: Among the 70 cases analyzed, we have identified 16 potential clusters of transmission: 8 for genotype 1a (23 cases involved), 1 for genotype 1b (3 cases) and 7 for genotype 4d (27 cases). Although the initial phylogenetic reconstruction suggested a local transmission cluster of HCV gt4d, our approach based on low genetic differentiation did not corroborate it. Indeed, gt4d strains formed 4 independent groups related to patients from other countries. Conclusions: Frequent clustering of HIV-positive MSM shows that HCV infection has spread through a local network in Barcelona. This outbreak is related to a large international HCV transmission network among MSM. Public health efforts are needed to reduce HCV transmission among this high-risk group
Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest)
<p>Abstract</p> <p>Background</p> <p>FibroTest and elastography have been validated as biomarkers of liver fibrosis in the most frequent chronic liver diseases and in the fibrosis screening of patients with diabetes. One challenge was to use them for estimating the prevalence of fibrosis, identifying independent risk factors and to propose screening strategies in the general population.</p> <p>Methods</p> <p>We prospectively studied 7,463 consecutive subjects aged 40 years or older. Subjects with presumed advanced fibrosis (FibroTest greater than 0.48) were re-investigated in a tertiary center.</p> <p>Results</p> <p>The sample characteristics were similar to those of the French population. FibroTest was interpretable in 99.6%. The prevalence of presumed fibrosis was 2.8%, (209/7,463), including cirrhosis in 0.3% (25/7,463); 105/209 (50%) subjects with presumed fibrosis accepted re-investigation. Fibrosis was confirmed in 50, still suspected in 27, indeterminate in 25 and not confirmed with false positive FibroTest or false negative elastography in 3 subjects. False negative rate of FibroTest estimated using elastography was 0.4% (3/766). The attributable causes for confirmed fibrosis were both alcoholic and nonalcoholic fatty liver disease (NAFLD) in 66%, NAFLD in 13%, alcohol in 9%, HCV in 6%, and other in 6%. Factors independently associated (all P < 0.003) with confirmed fibrosis were age, male gender, waist circumference, HCV antibody and alcohol consumption estimated using carbohydrate-deficient transferrin, enabling efficient screening-oriented strategies to be compared and proposed.</p> <p>Conclusions</p> <p>Biomarkers have permitted to estimate prevalence of advanced fibrosis around 2.8% in a general population aged 40 years or older, and several risk factors which may be used for the validation of selective or non-selective screening strategies.</p
AA. VV., Los Dominicos y el Nuevo Mundo, Actas del III Congreso Internacional, ed. Deimos, Madrid 1991, 852 pp., 17 x 24. [RECENSIĂN]
BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naĂŻve to treatment with a baseline HCV RNA/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks.
AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting.
METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naĂŻve genotype 1 HCV patients.
RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables.
CONCLUSIONS: In treatment-naĂŻve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen
Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.
BACKGROUND
Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial.
METHODS
For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population.
FINDINGS
The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed.
INTERPRETATION
Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM.
FUNDING
National Institutes of Health and Dr. C.J. Vaillant Fonds
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