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Search Results: 1 - 10 of 402627 matches for " On behalf of the TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M) "
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Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis
Awachana Jiamsakul, Rami Kantor, Patrick CK Li, Sunee Sirivichayakul, Thira Sirisanthana, Pacharee Kantipong, Christopher KC Lee, Adeeba Kamarulzaman, Winai Ratanasuwan, Rossana Ditangco, Thida Singtoroj, Somnuek Sungkanuparph, On behalf of the TREAT Asia Studies to Evaluate ResistanceMonitoring Study (TASER-M)
BMC Research Notes , 2012, DOI: 10.1186/1756-0500-5-582
Abstract: Sequences from 1301 ARV-naive patients enrolled in the TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M) were analysed by both interpreting systems. Interpretations from both Stanford HIVdb and vircoTYPE? HIV-1 were initially grouped into 2 levels: susceptible and non-susceptible. Discrepancy was defined as a discordant result between the susceptible and non-susceptible interpretations from the two systems for the same ARV. Further analysis was performed when interpretations from both systems were categorised into 3 levels: susceptible, intermediate and resistant; whereby discrepancies could be categorised as major discrepancies and minor discrepancies. Major discrepancy was defined as having a susceptible result from one system and resistant from the other. Minor discrepancy corresponded to having an intermediate interpretation in one system, with a susceptible or resistant result in the other. The level of agreement was analysed using the prevalence adjusted bias adjusted kappa (PABAK).Overall, the agreement was high, with each ARV being in “almost perfect agreement”, using Landis and Koch’s categorisation. Highest discordance was observed for efavirenz (75/1301, 5.8%), all arising from susceptible Stanford HIVdb versus non-susceptible vircoTYPE? HIV-1 predictions. Protease Inhibitors had highest level of concordance with PABAKs all above 0.99, followed by Nucleoside Reverse Transcriptase Inhibitors with PABAKs above 0.97 and non-NRTIs with the lowest PABAK of 0.88. The 68/75 patients with discordant efavirenz results harboured the V179D/E mutations compared to 7/1226 with no efavirenz discrepancy (p-value <0.001). In the 3-level comparison, all but one of the discrepancies was minor.The two systems agreed well with lowest concordance observed for efavirenz. When interpreting HIVDR, especially in non-B subtypes, clinical correlation is crucial, in particular when efavirenz resistance is interpreted based on V179D/E.In recent years, developing
Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients
Sasisopin Kiertiburanakul, Romanee Chaiwarith, Sunee Sirivichayakul, Rossana Ditangco, Awachana Jiamsakul, Patrick C. K. Li, Pacharee Kantipong, Christopher Lee, Winai Ratanasuwan, Adeeba Kamarulzaman, Annette H. Sohn, Somnuek Sungkanuparph, for the TREAT Asia Studies to Evaluate Resistance Surveillance and Monitoring Studies
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062057
Abstract: Background The emergence and transmission of HIV-1 drug resistance (HIVDR) has raised concerns after rapid global antiretroviral therapy (ART) scale-up. There are limited data on the epidemiology of primary HIVDR in resource-limited settings in Asia. We aimed to determine the prevalence and compare the distribution of HIVDR in a cohort of ART-na?ve Asian patients with recent and chronic HIV-1 infection. Methods Multicenter prospective study was conducted in ART-na?ve patients between 2007 and 2010. Resistance-associated mutations (RAMs) were assessed using the World Health Organization 2009 list for surveillance of primary HIVDR. Results A total of 458 patients with recent and 1,340 patients with chronic HIV-1 infection were included in the analysis. The overall prevalence of primary HIVDR was 4.6%. Recently infected patients had a higher prevalence of primary HIVDR (6.1% vs. 4.0%, p = 0.065) and frequencies of RAMs to protease inhibitors (PIs; 3.9% vs. 1.0%, p<0.001). Among those with recent infection, the most common RAMs to nucleoside reverse transcriptase inhibitors (NRTIs) were M184I/V and T215D/E/F/I/S/Y (1.1%), to non-NRTIs was Y181C (1.3%), and to PIs was M46I (1.5%). Of patients with chronic infection, T215D/E/F/I/S/Y (0.8%; NRTI), Y181C (0.5%; non-NRTI), and M46I (0.4%; PI) were the most common RAMs. K70R (p = 0.016) and M46I (p = 0.026) were found more frequently among recently infected patients. In multivariate logistic regression analysis in patients with chronic infection, heterosexual contact as a risk factor for HIV-1 infection was less likely to be associated with primary HIVDR compared to other risk categories (odds ratio 0.34, 95% confidence interval 0.20–0.59, p<0.001). Conclusions The prevalence of primary HIVDR was higher among patients with recent than chronic HIV-1 infection in our cohort, but of borderline statistical significance. Chronically infected patients with non-heterosexual risks for HIV were more likely to have primary HIVDR.
The Barcelona Declaration from the World Alliance against Antibiotic Resistance: engagement of intensivists
Jean M Carlet, Antonio Artigas, Michael S Niederman, Antoni Torres, on behalf of World Alliance against Antibiotic Resistance
Critical Care , 2012, DOI: 10.1186/cc11427
Abstract: Microorganisms resistant to almost every antibiotic are already present in the ICUs of many countries, requiring the use of old and toxic antibiotics such as colistin [2]. We were usually saved from resistance in the past by the regular introduction of new compounds, but this time the pipeline is almost dry. No new antibacterial agent active against Gram-negative bacteria is expected in the next 5 years. We are therefore back in the situation of 50 years ago, and the risk of large epidemic outbreaks leading to a real pandemic with those multi-resistant bacteria is real. The European Centre for Diseases Control estimate is that 25,000 patients in Europe might die from infections due to resistant organisms every year. In most countries, people use too many antibiotics empirically - in particular, to treat viral infections such as pharyngitis, bronchitis, or urinary colonisation. To treat severe infections in the ICU, and for the sake of their patients, prescribers use broad-spectrum antibiotics empirically in order to prevent treatment failures - but they seldom re-evaluate this initial therapy even when it is not necessary or too broad, and they often treat for too long.It is time to react vigorously in order to protect and save antibiotics, and try to break this downward spiral of resistance. A strong cooperation between healthcare professionals - in both human and animal medicine - and consumers is therefore needed, providing simple but powerful and convincing information to the politicians and the public. Antibiotics must have a special status, with specific rules, regulations, and controls. Diagnostic tests must be developed to help clinicians know when not to treat, and to focus antibacterial therapy only on bacterial infections. Research must be facilitated, particularly to accelerate the development of new compounds. Infection control must be upgraded, in particular to emphasise the use of hand-rub alcoholic solutions, in the hospitals and in the community. Th
Rates and Factors Associated with Major Modifications to First-Line Combination Antiretroviral Therapy: Results from the Asia-Pacific Region
Stephen Wright, Mark A. Boyd, Evy Yunihastuti, Matthew Law, Thira Sirisanthana, Jennifer Hoy, Sanjay Pujari, Man Po Lee, Kathy Petoumenos, on behalf of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific HIV Observational Database (APHOD)
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064902
Abstract: Background In the Asia-Pacific region many countries have adopted the WHO’s public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region. Methods We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country’s per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class. Results A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44–0.52), 0.33 (0.30–0.36) and 0.21 (0.18–0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. Conclusions Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was associated with increased modifications to first-line ART.
Impact of cigarette smoking on the relationship between body mass index and coronary heart disease: a pooled analysis of 3264 stroke and 2706 CHD events in 378579 individuals in the Asia Pacific region
The Asia Pacific Cohort Studies Collaboration
BMC Public Health , 2009, DOI: 10.1186/1471-2458-9-294
Abstract: A pooled analysis of individual participant data from 38 cohorts, involving 378,579 participants. Hazards ratios (HRs) and 95% confidence intervals (CIs) for BMI by cigarette smoking status were estimated using Cox proportional hazard models.During a mean follow-up of 3.8 years, 2706 CHD and 3264 strokes were recorded. There was a log-linear, positive relationship of BMI with CHD and stroke in both smokers and non-smokers with evidence of a synergistic effect of smoking on the association between BMI and CHD only: HRs (95% CIs) associated with a 2 kg/m2 higher BMI were 1.13 (1.10 – 1.17) in current smokers and 1.09 (1.06 – 1.11) in non-smokers (p-value for interaction = 0.04).Smoking amplifies the positive association between BMI and CHD but not stroke. If confirmed, these results suggest that effective strategies that target smoking cessation and weight loss are likely to have a greater impact than anticipated on reducing the burden of CHD.It has been well documented that overweight and obesity is now a global epidemic with relatively few countries unaffected. The World Health Organisation (WHO) has estimated that 1.6 billion people are overweight worldwide, which, for the first time, exceeds those who are undernourished [1,2]. Moreover, low- and middle-income countries, such as China that traditionally had one of the leanest populations, are rapidly approaching the prevalence of overweight observed in more developed regions [3]. Although the prevalence of smoking in the Western world has progressively declined over the past forty years – due largely to effective and comprehensive tobacco control measures – tobacco consumption remains high in many countries across Asia where about 40–70% of men smoke [4]. This is a likely consequence of the low level of awareness of the health hazards associated with smoking combined with a low use of smoking cessation aids and aggressive promotion of smoking by the tobacco industry in many countries in Asia, such as China [5].Smok
The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection
Emma Hodcroft,Jarrod D. Hadfield,Esther Fearnhill,Andrew Phillips,David Dunn,Siobhan O'Shea,Deenan Pillay,Andrew J. Leigh Brown ,on behalf of the UK HIV Drug Resistance Database and the UK CHIC Study
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004112
Abstract: Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8–8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.
Ashtrays and Signage as Determinants of a Smoke-Free Legislation’s Success
Constantine I. Vardavas, Israel Agaku, Evridiki Patelarou, Nektarios Anagnostopoulos, Chrysanthi Nakou, Vassiliki Dramba, Gianna Giourgouli, Paraskevi Argyropoulou, Antonis Antoniadis, Konstantinos Gourgoulianis, Despoina Ourda, Lambros Lazuras, Monique Bertic, Christos Lionis, Gregory Connolly, Panagiotis Behrakis, on behalf of the Hellenic Air Monitoring Study Investigators
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072945
Abstract: Introduction Successful smoke-free legislation is dependent on political will, enforcement and societal support. We report the success and pitfalls of a non-enforced nationwide smoke-free legislation in Greece, as well as ways in which compliance and enforcement-related factors, including ashtrays and signage, may impact indoor secondhand smoke (SHS) concentrations. Methods A follow-up study of venues (n = 150, at baseline, n = 75 at 2-year follow-up) in Greece assessed indoor particulate matter with a diameter less than 2.5 micrometers (PM2.5) concentrations attributable to SHS smoke every six months for two years (n = 455 venue/measurements). Results Following the implementation of the 2010 smoke-free legislation, mean PM2.5 concentrations attributable to SHS fell from 175.3 μg/m3 pre-ban to 84.52 μg/m3 immediately post-ban, increasing over subsequent waves (103.8 μg/m3 and 158.2 μg/m3 respectively). Controlling for potential influential factors such as ventilation, time of day, day of week, city and venue type, all post-ban measurements were still lower than during the pre-ban period (Wave 2 beta: ?118.7, Wave 3 beta: ?87.6, and Wave 4 beta: ?69.9). Outdoor or indoor signage banning smoking was not found to affect SHS concentrations (beta: ?10.9, p = 0.667 and beta: ?18.1, p = 0.464 respectively). However, ashtray or ashtray equivalents were strong determinants of the existence of indoor SHS (beta: +67 μg/m3, p = 0.017). Conclusions While the public may be supportive of smoke-free legislation, adherence may decline rapidly if enforcement is limited or nonexistent. Moreover, enforcement agencies should also focus on the comprehensive removal of ashtray equivalents that could act as cues for smoking within a venue.
HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing Regimen
Joana Cavaco-Silva, Ana Abecasis, Ana Cláudia Miranda, José Po?as, Jorge Narciso, Maria Jo?o águas, Fernando Maltez, Isabel Almeida, Isabel Germano, António Diniz, Maria de Fátima Gon?alves, Perpétua Gomes, Celso Cunha, Ricardo Jorge Camacho, on behalf of the Portuguese HIV-2 Resistance Study Group
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092747
Abstract: To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-na?ve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from na?ve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.
Novel HIV-1 Recombinants Spreading across Multiple Risk Groups in the United Kingdom: The Identification and Phylogeography of Circulating Recombinant Form (CRF) 50_A1D
Geraldine M. Foster, John C. Ambrose, Stéphane Hué, Valerie C. Delpech, Esther Fearnhill, Ana B. Abecasis, Andrew J. Leigh Brown, Anna Maria Geretti, on behalf of the UK HIV Drug Resistance Database
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0083337
Abstract: Background An increase in non-B HIV-1 infections among men who have sex with men (MSM) in the United Kingdom (UK) has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies. Methods and Results A total of 55,556 pol (reverse transcriptase and protease) sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL). Overall 72 patients shared the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug users (IDUs). In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints), which has been classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST). This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a subtype B strain. Conclusions We report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around 1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B. These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously distinct MSM and heterosexual epidemics.
Livestock-Associated MRSA Carriage in Patients without Direct Contact with Livestock
Miranda M. L. van Rijen, Thijs Bosch, Erwin J. M. Verkade, Leo Schouls, Jan A. J. W. Kluytmans, on behalf of the CAM Study Group , the CAM Study Group
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100294
Abstract: Background Livestock-associated MRSA (MC398) has emerged and is related to an extensive reservoir in pigs and veal calves. Individuals with direct contact with these animals and their family members are known to have high MC398 carriage rates. Until now it was assumed that MC398 does not spread to individuals in the community without pig or veal calf exposure. To test this, we identified the proportion of MC398 in MRSA positive individuals without contact with pigs/veal calves or other known risk factors (MRSA of unknown origin; MUO). Methods In 17 participating hospitals, we determined during two years the occurrence of MC398 in individuals without direct contact with livestock and no other known risk factor (n = 271) and tested in a post analysis the hypothesis whether hospitals in pig-dense areas have higher proportions of MC398 of all MUO. Results Fifty-six individuals (20.7%) without animal contact carried MC398. In hospitals with high pig-densities in the adherence area, the proportion of MC398 of all MUO was higher than this proportion in hospitals without pigs in the surroundings. Conclusions One fifth of the individuals carrying MUO carried MC398. So, MC398 is found in individuals without contact to pigs or veal calves. The way of transmission from the animal reservoir to these individuals is unclear, probably by human-to-human transmission or by exposure to the surroundings of the stables. Further research is needed to investigate the way of transmission.
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