Center for Excellence in AIDS

Vancouver, Canada

Center for Excellence in AIDS

Vancouver, Canada
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Jones B.R.,Simon Fraser University | Jones B.R.,Center for Excellence in AIDS | Poon A.F.Y.,Center for Excellence in AIDS | Poon A.F.Y.,University of British Columbia | Poon A.F.Y.,University of Western Ontario
Bioinformatics | Year: 2017

Phylogenetic trees encode the evolutionary distances between species or populations. With sufficient information, these evolutionary distances can be rescaled over time to provide estimates of the dates of the most recent ancestors of the species. Here we present the R program, divergence-time analysis software, which uses a maximum-likelihood method to estimate the dates of the internal nodes of a phylogenetic tree. © The Author 2016.

Jetz W.,Yale University | Jetz W.,Imperial College London | Thomas G.H.,University of Sheffield | Joy J.B.,Yale University | And 5 more authors.
Current Biology | Year: 2014

Background Integrated, efficient, and global prioritization approaches are necessary to manage the ongoing loss of species and their associated function. "Evolutionary distinctness" measures a species' contribution to the total evolutionary history of its clade and is expected to capture uniquely divergent genomes and functions. Here we demonstrate how such a metric identifies species and regions of particular value for safeguarding evolutionary diversity. Results Among the world's 9,993 recognized bird species, evolutionary distinctness is very heterogeneously distributed on the phylogenetic tree and varies little with range size or threat level. Species representing the most evolutionary history over the smallest area (those with greatest "evolutionary distinctness rarity") as well as some of the most imperiled distinct species are often concentrated outside the species-rich regions and countries, suggesting they may not be well captured by current conservation planning. We perform global cross-species and spatial analyses and generate minimum conservation sets to assess the benefits of the presented species-level metrics. We find that prioritizing imperiled species by their evolutionary distinctness and geographic rarity is a surprisingly effective and spatially economical way to maintain the total evolutionary information encompassing the world's birds. We identify potential conservation gaps in relation to the existing reserve network that in particular highlight islands as effective priority areas. Conclusions The presented distinctness metrics are effective yet easily communicable and versatile tools to assist objective global conservation decision making. Given that most species will remain ecologically understudied, combining growing phylogenetic and spatial data may be an efficient way to retain vital aspects of biodiversity. © 2014 The Authors.

Werb D.,Center for Excellence in AIDS | Buxton J.,Center for Disease Control | Shoveller J.,University of British Columbia | Richardson C.,University of British Columbia | And 2 more authors.
Drug and Alcohol Dependence | Year: 2013

Background: Injection drug use has been identified as a key source of morbidity and mortality, primarily from overdose and the transmission of blood-borne diseases such as HIV. Experts have therefore called for the prioritization of resources toward the prevention of injection drug use. However, these strategies have not been systematically assessed. Methods: PRISMA guidelines were used to systematically review and extract findings from the peer-reviewed literature evaluating the effectiveness of interventions to prevent injecting initiation. We searched 10 English language electronic databases (PubMed, PsycINFO, EMBASE, Cochrane CENTRAL, CINAHL, Web of Science, TOXNET, AIDSLINE, AMED and ERIC), the Internet (Google, Google Scholar), and article reference lists, from database inception to June 1st, 2012. Results: Overall, out of 384 studies identified in the initial search, eight met the inclusion criteria. Studies evaluated four different types of interventions: social marketing, peer-based behavior modification, treatment, and drug law enforcement. Four studies observed a significant effect of the intervention on reducing rates of injecting initiation. Peer-based behavior modification and addiction treatment interventions were found to be most effective. Two of three studies assessing the impact of drug law enforcement on patterns of injecting initiation found no impact on injecting initiation, while one study reported inconclusive results. Conclusion: There exists a limited scientific literature on strategies to prevent injecting initiation. Resources should be allocated toward increased research and development of effective interventions to prevent this phenomenon. © 2013 Elsevier Ireland Ltd.

Dahabieh M.S.,University of British Columbia | Ooms M.,Mount Sinai School of Medicine | Brumme C.,Center for Excellence in AIDS | Taylor J.,Center for Excellence in AIDS | And 3 more authors.
Retrovirology | Year: 2014

Background: Molecular latency allows HIV-1 to persist in resting memory CD4+ T-cells as transcriptionally silent provirus integrated into host chromosomal DNA. Multiple transcriptional regulatory mechanisms for HIV-1 latency have been described in the context of progressive epigenetic silencing and maintenance. However, our understanding of the determinants critical for the establishment of latency in newly infected cells is limited.Results: In this study, we used a recently described, doubly fluorescent HIV-1 latency model to dissect the role of proviral integration sites and cellular activation state on direct non-productive infections at the single cell level. Proviral integration site mapping of infected Jurkat T-cells revealed that productively and non-productively infected cells are indistinguishable in terms of genomic landmarks, surrounding epigenetic landscapes, and proviral orientation relative to host genes. However, direct non-productive infections were inversely correlated with both cellular activation state and NFκB activity. Furthermore, modulating NFκB with either small molecules or by conditional overexpression of NFκB subunits was sufficient to alter the propensity of HIV-1 to directly enter a non-productive latent state in newly infected cells. Importantly, this modulatory effect was limited to a short time window post-infection.Conclusions: Taken together, our data suggest that cellular activation state and NFκB activity during the time of infection, but not the site of proviral integration, are important regulators of direct HIV-1 non-productive infections. © 2014 Dahabieh et al.; licensee BioMed Central Ltd.

Sluis-Cremer N.,University of Pittsburgh | Huber K.D.,University of Pittsburgh | Brumme C.J.,Center for Excellence in AIDS | Brumme C.J.,University of British Columbia | And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

We characterized the relative fitness of multiple nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-resistant HIV-1 variants in the presence of etravirine (ETV), rilpivirine (RPV), and/or the nucleoside RT inhibitor emtricitabine (FTC) by simultaneous competitive culture and 454 deep sequencing. The E138A substitution, typically associated with decreased virologic responses to ETV- and RPV-containing regimens, confers a clear fitness advantage to the virus in the presence of FTC and decreases FTC susceptibility 4.7-fold. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Pakula B.,University of British Columbia | Shoveller J.,University of British Columbia | Shoveller J.,Center for Excellence in AIDS | Ratner P.A.,University of British Columbia | Carpiano R.,University of British Columbia
American Journal of Public Health | Year: 2016

Objectives. To investigate the prevalence and co-occurrence of heavy drinking, anxiety, and Mood disorders among Canadians who self-identified as gay, lesbian, bisexual, or heterosexual. Methods. Pooled data from the 2007 to 2012 cycles of the Canadian Community Health Survey (n = 222 548) were used to fit logistic regression models controlling for sociodemographic characteristics. Results. In adjusted logistic regression models, gay or lesbian respondents had greater odds than heterosexual respondents of reporting anxiety disorders, mood disorders, and anxiety-mood disorders. Bisexual respondents had greater odds of reporting anxiety disorders, mood disorders, anxiety-mood disorders, and heavy drinking. Gay or lesbian and bisexual respondents had greater odds than heterosexuals of reporting co-occurring anxiety or mood disorders and heavy drinking. The highest rates of disorders were observed among bisexual respondents, with nearly quadruple the rates of anxiety, mood, and combined anxiety and mood disorders relative to heterosexuals and approximately twice the rates of gay or lesbian respondents. Conclusions. Members of sexual minority groups in Canada, in particular those self identifying as bisexual, experience disproportionate rates of anxiety and mood disorders, heavy drinking, and co-occurring disorders.

O'Shaughnessy M.V.,Center for Excellence in AIDS | Hogg R.S.,Center for Excellence in AIDS | Hogg R.S.,Simon Fraser University | Strathdee S.A.,University of California at San Diego | And 2 more authors.
Current HIV/AIDS Reports | Year: 2012

The scope and scale of the HIV outbreak that occurred among injection drug users in Vancouver in the late 1990s was unprecedented and resulted in some 2,000 new HIV infections, with incidence rates reaching 18 per 100 person-years. This outbreak, localized mainly in one neighbourhood, cost the Canadian health care system more than 1 billion dollars to diagnose, care and treat. A number of factors combined to stabilize HIV incidence: 1) HIV prevalence became saturated among those at highest risk; 2) several public health policies focused on drug users were implemented, including increased and additional decentralized needle exchange programs, expanded methadone maintenance services, better addiction treatment services, improved housing, and mental health programs; and 3) increased access and expansion of Highly Active Antiretroviral Therapy. To ensure that a similar outbreak never occurs again in Vancouver and other cities, future health policy must consider the political, psychosocial and socioeconomic factors that contributed to this outbreak. These policies must address the unintended adverse consequences of past policies and their repercussions for marginalized individuals living in this community and beyond. © 2012 Springer Science+Business Media, LLC.

Poon A.F.Y.,Center for Excellence in AIDS | Poon A.F.Y.,University of British Columbia | Poon A.F.Y.,Simon Fraser University
Molecular Biology and Evolution | Year: 2015

The shapes of phylogenetic trees relating virus populations are determined by the adaptation of viruses within each host, and by the transmission of viruses among hosts. Phylodynamic inference attempts to reverse this flow of information, estimating parameters of these processes from the shape of a virus phylogeny reconstructed from a sample of genetic sequences from the epidemic. A key challenge to phylodynamic inference is quantifying the similarity between two trees in an efficient and comprehensive way. In this study, I demonstrate that a new distance measure, based on a subset tree kernel function from computational linguistics, confers a significant improvement over previous measures of tree shape for classifying trees generated under different epidemiological scenarios. Next, I incorporate this kernel-based distance measure into an approximate Bayesian computation (ABC) framework for phylodynamic inference. ABC bypasses the need for an analytical solution of model likelihood, as it only requires the ability to simulate data from the model. I validate this "kernel-ABC" method for phylodynamic inference by estimating parameters from data simulated under a simple epidemiological model. Results indicate that kernel-ABC attained greater accuracy for parameters associated with virus transmission than leading software on the same data sets. Finally, I apply the kernel-ABC framework to study a recent outbreak of a recombinant HIV subtype in China. Kernel-ABC provides a versatile framework for phylodynamic inference because it can fit a broader range of models than methods that rely on the computation of exact likelihoods. © 2015 The Author.

Swenson L.C.,Center for Excellence in AIDS | Min J.E.,Center for Excellence in AIDS | Woods C.K.,Center for Excellence in AIDS | Cai E.,Center for Excellence in AIDS | And 4 more authors.
AIDS | Year: 2014

Background: The clinical implications of emergent HIV drug resistance on samples with low-level viraemia (LLV <1000 copies/ml) remain unclear. We undertook the present analysis to evaluate the impact of emergent HIV drug resistance at LLV on the risk of subsequent virologic failure. Methods: One thousand, nine hundred and sixty-five patients had genotype results at LLV. Risk of virologic failure (≥1000 copies/ml) after LLV was evaluated by Kaplan-Meier analysis and Cox proportional hazards regression. Resistance was assessed using the Stanford algorithm or virtual phenotypes. Patients were grouped into four susceptibility categories ('GSS' or 'vPSS') during LLV, corresponding to the number of 'active' drugs prescribed: <1; 1-1.5; 2-2.5; and ≥3. Results: A total of 1702 patients with follow-up on constant therapy were eligible for analysis. Participants excluded due to changing therapy or loss to follow-up before their next observation had mostly similar characteristics to included participants. There was a 'dose-dependent' increase in the hazard ratio for virologic failure with susceptibility categories at LLV. Compared with a GSS of at least 3, hazard ratios for virologic failure were 1.4 for GSS 2-2.5; 2.0 for GSS 1-1.5; and 3.0 for GSS less than 1 (P<0.001). Numerous sensitivity analyses confirmed these findings. Conclusion: Our results demonstrate that emergent HIV drug resistance at LLV is strongly associated with subsequent virologic failure. Furthermore, we uncovered a 'dose-dependent' increase in the hazard ratio for virologic failure with decreasing GSS estimated at the time of LLV. On the basis of these findings, we propose that resistance genotyping be encouraged for HIV-infected individuals on antiretroviral therapy experiencing low-level viraemia. © 2014 Wolters Kluwer Health - Lippincott Williams & Wilkins.

Gupta S.,Independent Consultant | Williams B.,South African Center for Epidemiological Modelling and Analysis | Montaner J.,Center for Excellence in AIDS
Current HIV/AIDS Reports | Year: 2014

This article reviews the antiretroviral therapy (ART) initiation criteria from published national guidelines for 94 countries (representing 86 % of global HIV burden) and compares them with the 2013 World Health Organization (WHO) ART guidelines. As of 31st of July 2014, 19 countries have adopted the WHO-recommended CD4 eligibility criteria of ≤500 cells/mm3, while seven have opted to treat irrespective of CD4 cell count (“test and treat”). Together, these 26 countries represent 27 % of 2013 global HIV burden. Additionally, test and treat is recommended for selected groups of HIV-positive individuals, namely, (a) people with tuberculosis in 58 countries, (b) pregnant women in 42 countries, (c) people with liver disease due to hepatitis B co-infection in 52 countries, (d) serodiscordant couples in 35 countries and (e) children below 5 years in nine countries. Global access to treatment has improved; however in 2013, ART coverage was 12.9 million or 37 % of people living with HIV. Rapidly translating new science into policy is a critical component of the HIV response. Adapting and implementing the 2013 WHO treatment recommendations are necessary to prevent unnecessary illness, death, HIV transmission and costs. © 2014, Springer Science+Business Media New York.

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