Dataset Information

Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis.

ABSTRACT: Background:Integrase strand transfer inhibitors (INSTIs) are highly efficacious and well tolerated antiretrovirals with fewer adverse side-effects relative to other classes of antiretrovirals. The use of INSTIs raltegravir, elvitegravir, and dolutegravir has increased dramatically over recent years. However, there is limited information about the evolution and prevalence of INSTI resistance mutations in clinical human immunodeficiency virus populations. Methods:Human immunodeficiency virus-1-positive individuals ?19 years were included if they received ?1 dispensed prescription of antiretroviral therapy (ART) in British Columbia between 2009 and 2016 (N = 9358). Physician-ordered drug resistance tests were analyzed and protease inhibitor (PI), reverse-transcriptase inhibitor (RT), and INSTI resistance were defined as having ?1 sample with a combined, cumulative score ?30 by Stanford HIV Drug Resistance Algorithm version 7.0.1. Results:Although most ART-treated individuals were tested for PI and RT resistance, INSTI resistance testing lagged behind the uptake of INSTIs among INSTI-treated individuals (11% in 2009; 34% in 2016). The prevalence of INSTI resistance was relatively low, but it increased from 1 to 7 per 1000 ART-treated individuals between 2009 and 2016 (P < .0001, R2 = 0.98). Integrase strand transfer inhibitor resistance mutations increased at integrase codons 66, 97, 140, 148, 155, and 263. Conclusions:The prevalence of INSTI resistance remains low compared with PI and RT resistance in ART-treated populations but is expanding with increased INSTI use.

SUBMITTER: Kamelian K

PROVIDER: S-EPMC6419991 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis.

Kamelian Kimia K Lepik Katherine J KJ Chau William W Yip Benita B Zhang Wendy W WW Lima Viviane Dias VD Robbins Marjorie A MA Woods Conan C Olmstead Andrea A Joy Jeffrey B JB Barrios Rolando R Harrigan P Richard PR

Open forum infectious diseases 20190212 3

<h4>Background</h4>Integrase strand transfer inhibitors (INSTIs) are highly efficacious and well tolerated antiretrovirals with fewer adverse side-effects relative to other classes of antiretrovirals. The use of INSTIs raltegravir, elvitegravir, and dolutegravir has increased dramatically over recent years. However, there is limited information about the evolution and prevalence of INSTI resistance mutations in clinical human immunodeficiency virus populations.<h4>Methods</h4>Human immunodeficie ...[more]

PMID: 30895202

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Project description:There has been no systematic review of the prevalence of transmitted integrase strand transfer inhibitor (INSTI) resistance. We systematically searched the English-language PubMed database and GenBank to identify studies published since 2010 reporting 50 or more INSTI-naive HIV-1-infected adults undergoing integrase genotyping. We extracted data related to country, sample year, specimen type, sequencing method, and subtype. For studies with sequences in GenBank, we determined the prevalence of three categories of INSTI-associated resistance mutations: (1) nonpolymorphic INSTI-selected drug resistance mutations (DRMs) that we refer to as surveillance DRMs; (2) rarely selected nonpolymorphic INSTI-associated DRMs; and (3) common polymorphic accessory INSTI-selected DRMs. A total of 103 studies met inclusion criteria including 75 studies in GenBank containing integrase sequences from 16,481 INSTI-naive persons. The median sample year was 2013 (interquartile range: 2008-2014). The prevalence of INSTI surveillance DRMs, rarely selected DRMs, and common polymorphic accessory INSTI-selected DRMs were 0.5%, 0.8%, and 6.2%, respectively. There was no association between the presence of nonpolymorphic surveillance DRM and region, sample year, or subtype. Two surveillance DRMs, E138K and R263K occurred in 0.15% and 0.10% of naive sequences, respectively. Several lines of evidence suggested that the 0.5% prevalence of surveillance DRMs partly reflects the cumulative natural occurrence of these mutations in the absence of selective drug pressure. There was an unexplained temporal increase in the proportion of sequences with polymorphic accessory mutations. The prevalence of INSTI-associated surveillance DRMs is low even in regions where INSTIs have been a major component of antiretroviral therapy for several years. The presence of INSTI-associated surveillance DRMs in INSTI-naive persons likely results from actual cases of transmitted INSTI resistance and from a low background level reflecting the cumulative rare natural occurrence of several nonpolymorphic mutations.

Project description:OBJECTIVES:A current diagnosis of asthma cannot be objectively confirmed in many patients with physician-diagnosed asthma. Estimates of resource use in overdiagnosed cases of asthma are necessary to measure the burden of overdiagnosis and to evaluate strategies to reduce this burden. We assessed differences in asthma-related healthcare resource use between patients with a confirmed asthma diagnosis and those with asthma ruled out. DESIGN:Population-based, prospective cohort study. SETTING:Participants were recruited through random-digit dialling of both landlines and mobile phones in the province of British Columbia, Canada. PARTICIPANTS:We included 345 individuals ≥12 years of age with a self-reported physician diagnosis of asthma. The diagnosis of asthma was reassessed at the end of 12 months of follow-up using a structured algorithm, which included a bronchodilator reversibility test, methacholine challenge test, and if necessary medication tapering and a second methacholine challenge test. PRIMARY AND SECONDARY OUTCOME MEASURES:Self-reported annual asthma-related direct healthcare costs (2017 Canadian dollars), outpatient physician visits and medication use from the perspective of the Canadian healthcare system. RESULTS:Asthma was ruled out in 86 (24.9%) participants. The average annual asthma-related direct healthcare costs for participants with confirmed asthma were $C497.9 (SD $C677.9) and for participants with asthma ruled out, $C307.7 (SD $C424.1). In the adjusted analyses, a confirmed diagnosis was associated with higher direct healthcare costs (relative ratio (RR)=1.60, 95% CI 1.14 to 2.22), increased rate of specialist visits (RR=2.41, 95% CI 1.05 to 5.40) and reliever medication use (RR=1.62, 95% CI 1.09 to 2.35), but not primary care physician visits (p=0.10) or controller medication use (p=0.11). CONCLUSIONS:A quarter of individuals with a physician diagnosis of asthma did not have asthma after objective re-evaluation. These participants still consumed a significant amount of asthma-related healthcare resources. The population-level economic burden of asthma overdiagnosis could be substantial.

Project description:Legionella spp. present in some human-made water systems can cause Legionnaires' disease in susceptible individuals. Although legionellae have been isolated from the natural environment, variations in the organism's abundance over time and its relationship to aquatic microbiota are poorly understood. Here, we investigated the presence and diversity of legionellae through 16S rRNA gene amplicon and metagenomic sequencing of DNA from isolates collected from seven sites in three watersheds with varied land uses over a period of 1 year. Legionella spp. were found in all watersheds and sampling sites, comprising up to 2.1% of the bacterial community composition. The relative abundance of Legionella tended to be higher in pristine sites than in sites affected by agricultural activity. The relative abundance levels of Amoebozoa, some of which are natural hosts of legionellae, were similarly higher in pristine sites. Compared to other bacterial genera detected, Legionella had both the highest richness and highest alpha diversity. Our findings indicate that a highly diverse population of legionellae may be found in a variety of natural aquatic sources. Further characterization of these diverse natural populations of Legionella will help inform prevention and control efforts aimed at reducing the risk of Legionella colonization of built environments, which could ultimately decrease the risk of human disease. IMPORTANCE Many species of Legionella can cause Legionnaires' disease, a significant cause of bacterial pneumonia. Legionella in human-made water systems such as cooling towers and building plumbing systems are the primary sources of Legionnaires' disease outbreaks. In this temporal study of natural aquatic environments, Legionella relative abundance was shown to vary in watersheds associated with different land uses. Analysis of the Legionella sequences detected at these sites revealed highly diverse populations that included potentially novel Legionella species. These findings have important implications for understanding the ecology of Legionella and control measures for this pathogen that are aimed at reducing human disease.

Dataset Information

Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis.

Publications

Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis.

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