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Search Results: 1 - 10 of 244 matches for " The TREAT Asia HIV Observational Database "
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Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD)
Preeyaporn Srasuebkul, Alexandra Calmy, Jialun Zhou, Nagalingeswaran Kumarasamy, Matthew Law, Poh Lim, The TREAT Asia HIV Observational Database
AIDS Research and Therapy , 2007, DOI: 10.1186/1742-6405-4-18
Abstract: Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen.A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year.In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 – 1.96), p < 0.001, RR 3.39 (2.76 – 4.16) p < 0.001, RR 6.37 (4.51 – 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 – 0.99), p = 0.035, RR 0.77 (0.61 – 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 – 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 – 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively.Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation.In South and South-East Asia the nu
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.
Determinants of Suicide and Accidental or Violent Death in the Australian HIV Observational Database
Hamish McManus, Kathy Petoumenos, Teo Franic, Mark D. Kelly, Jo Watson, Catherine C. O’Connor, Mark Jeanes, Jennifer Hoy, David A. Cooper, Matthew G. Law, on behalf of the Australian HIV Observational Database
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089089
Abstract: Background Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART. Methods We conducted a nested case-control study of suicide and accidental or violent death in the Australian HIV Observational Database (AHOD) between January 1999 and March 2012. For each case, 2 controls were matched by clinic, age, sex, mode of exposure and HIV-positive date to adjust for potential confounding by these covariates. Risk of suicide and accidental or violent death was estimated using conditional logistic regression. Results We included 27 cases (17 suicide and 10 violent/accidental death) and 54 controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds Ratio (OR) 5.86, 95% CI: 1.69–20.37), living alone (OR 3.26, 95% CI: 1.06–10.07), suicidal ideation (OR 6.55, 95% CI: 1.70–25.21), and >2 psychiatric/cognitive risk factors (OR 4.99, 95% CI: 1.17–30.65). CD4 cell count of >500 cells/μL (OR 0.25, 95% CI: 0.07–0.87) and HIV-positive date ≥1990 (1990–1999 (OR 0.31, 95% CI: 0.11–0.89), post-2000 (OR 0.08, 95% CI: 0.01–0.84)) were associated with decreased risk. CD4 cell count ≥500 cells/μL remained a significant predictor of reduced risk (OR 0.15, 95% CI: 0.03–0.70) in a multivariate model adjusted for employment status, accommodation status and HIV-positive date. Conclusions After adjustment for psychosocial factors, the immunological status of HIV-positive patients contributed to the risk of suicide and accidental or violent death. The number of psychiatric/cognitive diagnoses contributed to the level of risk but many psychosocial factors were not individually significant. These findings indicate a complex interplay of factors associated with risk of suicide and accidental or violent death.
CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load: A Longitudinal Cohort Study from COHERE
The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001194
Abstract: Background Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. Methods and Findings Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/μl and ending with either a measurement >500 copies/μl, the first of two consecutive measurements between 50–500 copies/μl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/μl (95% CI) of: 0.35 (0.30–0.40) for counts <200 cells/μl, 0.81 (0.71–0.92) for counts 200 to <350 cells/μl, 0.74 (0.66–0.83) for counts 350 to <500 cells/μl, and 0.96 (0.92–0.99) for counts ≥500 cells/μl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/μl. Conclusions Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/μl but still some slight benefit for those with a CD4 cell count ≥500 cells/μl. Please see later in the article for the Editors' Summary
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 Resistance – Monitoring 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.
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.
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.
Dynamic Service Discovery, Composition and Reconfiguration in a Model Mapping Business Process to Web Services  [PDF]
Zulqarnain Abdul Jabbar, Asia Samreen
Journal of Computer and Communications (JCC) , 2016, DOI: 10.4236/jcc.2016.49004
Abstract: In any organization where SOA has been implemented, all of the web services are registered in UDDI and users’ needs are served by using appropriate web services. So in this paper, we will try to discover a service from repository first that can provide the required output to the user. The process becomes difficult when a single service is not able to fulfill a user’s need and we need a combination of services to answer complex needs of users. In our paper, we will suggest a simpler approach for dynamic service composition using a graph based methodology. This will be a design time service composition. This approach uses the functional and non-functional parameters of the services to select the most suitable services for composition as per user’s need. This approach involves “service classification” on the basis of functional parameters, “service discovery” on the basis of user’s need and then “service composition” using the selected services on the basis of non-functional parameters like response time, cost, security and availability. Another challenge in SOA implementation is that, once the composition has performed, some services may become faulty at runtime and may stop the entire process of serving a user’s need. So, we will also describe a way of “dynamic service reconfiguration” in our approach that will enable us to identify and replace a faulty service that is violating the SLA or is not accessible anymore. This service reconfiguration is done without redoing or reconfiguring the entire composition. In the end, to simulate the proposed approach, we will represent a prototype application built on php 5.4 using My SQL database at backend.
The 26th Congress of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine, Tromso, Norway, 13-17 June 2001
Investigational Drugs database
Critical Care , 2001, DOI: 10.1186/cc1024
Abstract: The Congress took place at the northernmost academic center in the world, in the state-of-the art Tromso University Hospital. There were over 500 participants, mainly from Scandinavian countries, with approximately 50 invited participants from non-Scandinavian countries, primarily from Europe and the USA. The meeting was managed and organized by a local committee, chaired by the University of Tromso Professor of Anaesthesiology Dr Lars Bjertneas. Approximately 300 oral and poster presentations highlighted the latest progress in diverse areas of anaesthesiol-ogy and intensive care medicine from Scandinavia. Invited speakers held state-of-the art lectures in selected areas of pathophysiology and therapy. The meeting benefited from the support of various industry sponsors, and the abstracts of the meeting were published in a supplement of Acta Anesthesiologica Scandinavica.Sepsis represents a major cause of mortality, affecting 750,000 patients/year in the USA, with 2000 new cases identified each day and 700 deaths per year (2001 US statistics). Much interest focused on the haemostatic aspects of sepsis and septic shock. This interest stems partly from the recent results of a multicenter trial that demonstrated the beneficial effects and a significant survival benefit provided by APC infusion in septic patients. Dr P Laterre (University Clinic, St Luc, Belgium) provided a detailed overview of the recently completed clinical trial with APC (or Drotecogin alpha; 24 μg/kg per h for 4 days by intravenous infusion). In the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) study, a 1690-patient randomized trial that utilized inclusion criteria similar to those of the preceding anticytokine trials, the mortality rate in the placebo group was 30.8%, which decreased to 24.9% in the treatment group. This corresponds to a 6% reduction in mortality, which means that for every 16 patients treated with APC one can expect to save an additional life.That trial demonstrated no
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