BC Centre for Excellence in HIV/AIDS Archives - Page 3 of 4

Translation of next-generation sequencing to HIV treatment and prevention in British Columbia

Next-generation sequencing (NGS) is the automation of high-throughput DNA sequencing on a massive scale that is rapidly transforming biology and medicine. It can enable laboratories to detect small, but clinically significant, numbers of drug-resistant viruses in blood samples from infected individuals.

The lack of computational tools to process and interpret NGS data collected from rapidly-evolving populations such as HIV remains a major obstacle in the application of NGS to HIV treatment and prevention. Dr. Poon’s research will bridge this divide by developing computational methods for NGS analysis designed to address key issues in HIV prevention and treatment. He will share his software as a free resource to the basic and clinical research communities.

He will take advantage of resources available to him through the BC Centre for Excellence in HIV/AIDS (BC-CfE): an extensive archive of HIV plasma specimens; one of the world’s few NGS cores dedicated to HIV research; and his own expertise in molecular evolution and bioinformatic sequence analysis.

As part of his research, he is developing and validating a new method to reconstruct the time of HIV infection from NGS data. Using specimens from the BC-CfE, he will estimate times of HIV infection and reconstruct the historical trend of HIV incidence (the rate of new HIV infections) in BC. This will help assess the long-term impact of expanding access to HIV therapy in BC and identify other correlates of HIV incidence.

He will also use “phylogenetic” methods, which can infer the ancestral tree that relates observed genetic sequences, to reconstruct the history of HIV transmissions in BC. This will allow him to evaluate the impact of expanding access to HIV therapy in BC on the rate of transmitting drug-resistant HIV, and to characterize the variation in rates of HIV transmission over the course of the epidemic.

Finally, he will develop a new class of methods for analyzing NGS data to characterize the adaptation of HIV to the host-specific immune response, and to reconstruct the genetic sequence of the transmitted HIV strain. The results from these methods can provide key information for the development of HIV vaccine candidates – a core aim of HIV prevention research.

Responding to the health crisis among street-involved youth in Vancouver: Evidence to inform interventions and policy responses

Street-involved youth are extremely vulnerable to health-related harms resulting from high rates of illegal drug use and sexually-risky behaviour, poverty, and neglect, as well as precarious living conditions, either on the street or in risky relationships. There is an estimated 150,000 street youth in Canada, with approximately 40 percent reporting injection drug use. This puts street youth at a very high risk for sexually transmitted infections (STI) and hepatitis C (HCV) infection.

Dr. DeBeck’s research seeks to address gaps that exist in our understanding of how street youth are initiated in illegal drug use and the dynamic of how STI and HCV are transmitted.

Her work will examine individual (e.g. stimulant use), social (e.g. childhood trauma), structural (e.g. access and coverage of addiction treatment), and environmental (e.g. homelessness) factors and how they intersect to promote a “risk environment” that elevates sexual risk and drug-related harms.

The outcome of her analysis will be a body of evidence that can support the development and evaluation of behavioural and structural interventions to prevent sexual and drug-related harms among street-involved youth. Her work will also support clinical trials to address critical issues in the diagnosis and treatment of hepatitis C among street-involved youth.

Ultimately, the results of her work will help prevent high-risk drug use, infectious diseases and other health harms among street-involved youth. It will also provide critical guidance for the effective management and treatment of infectious diseases among street involved youth.

End of Award Update – April 2024

Results

Having dedicated research time through a Michael Smith/Providence Health Care Research Institute-St. Paul’s Hospital Scholar Award allowed Dr. DeBeck to build research networks and engage in inclusive collaborations through the At-Risk Youth Study (ARYS) cohort platform. As a Michael Smith Scholar she published more than 160 peer reviewed publications, 55 of which research trainees were the first author and she was the senior author. Dr. DeBeck has also been able to publish with nine different co-authors with lived or living experiences of substance use, the majority of whom identify as Indigenous. Her Scholar Award gave her time to network and collaborate with organizations like the Western Aboriginal Harm Reduction Society, the First Nations Health Authority, Vancouver Coastal Health and the BC Ministry of Mental Health and Addictions. She was also able to facilitate the creation of a program of ARYS Peer Research Associates (PRA) and more recently an Indigenous Peer Collaborators Circle to lead research involving Indigenous people who use drugs.

Impact

Collectively, Dr. DeBeck’s activities as a Michael Smith Scholar have contributed to a scientific evidence-based model that demonstrates that prevailing models of drug law enforcement are ineffective and carry serious unintended harms for structurally marginalized populations. Her work has documented that the criminalization of drug use hinders HIV prevention; incarceration is linked to a decreased likelihood of quitting drug injection and an increased likelihood of relapse into substance use; and incarceration has been discriminatory, disproportionately affecting young Indigenous people in Vancouver. Cumulatively, this body of work provides evidence that despite continuing to receive significant government funding, drug law enforcement has not been demonstrated to be effective and has serious unintended negative harms. This paves the way for evidence-based policy reforms that are not punitive in nature.

Other research contributions include characterizing the early stages of problematic substance use which underscores the role of social determinants of health (e.g., adverse childhood events, child welfare exposure, and intergenerational trauma) as drivers of substance. Documenting the role of social determinants of substance use draws attention to the necessity of policy reforms that attend to social and structural drivers of risk and counters popular narratives of individual moral failings and individual responsibility for substance use.

Contributions during her Scholar Award also include work on addiction treatment engagement that inform responses to the drug toxicity poisoning crisis. The policy implications of this body of work are that addiction treatment, despite demonstrated clinical effectiveness for some people who use drugs, has limited overall reach and impact. Based on these studies, expansion of addiction treatment cannot be expected to adequately respond to the toxic drug crisis. Additional interventions that span prevention and harm reduction, including addressing the toxic drug supply, are needed. Monitoring and evaluating innovative models that make regulated drugs or “safer supply” available is a critical next step for drug policy development and one that the ARYS cohort is ideally positioned to contribute to.

Another impact of Dr. DeBeck’s Scholar Award was the opportunity to leverage drug consumption data from the ARYS cohort and be part of the working group that drafted the City of Vancouver’s 2021 application to Health Canada for the decriminalization of drug possession. The introduction of drug decriminalizing has been symbolically monumental as it reflects the growing understanding that drug criminalization has been ineffective and harmful and different approaches to substance use are needed.

Potential Influence

Holding a Scholar Award allowed the ARYS cohort research platform to thrive under the leadership of Dr. DeBeck. It also gave her the opportunity to build critical research networks and collaborations that positioned her to transition to a CIHR Applied Public Health Chair and Dorothy Killam Fellowship in 2024. With this foundation in place, she is well positioned to continue to generate responsive, high-quality data to inform substance use interventions and drug policy. Current priorities are to engage in community-based collaboration with people who use drugs and government partners, to evaluate interventions and inform policy responses to prevent toxic drug poisonings, increase service engagement, and promote health and wellness among street-involved young people who use drugs in Vancouver and beyond.

Next Steps

With a CIHR APHC and Dorothy Killam Fellowship Dr. DeBeck can continue a research-intensive trajectory. Collaboration with ARYS PRAs and a newly formed Indigenous Peer Collaborator Circle are ongoing. Data sharing with government and community partners is also continuing with multiple research products under development.

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HIV risk environments among illicit drug users: A longitudinal ethno-spatial approach

Dr. Will Small’s research program will examine the influence of social, structural and physical environments upon illicit drug users’ HIV risk behaviour and HIV treatment-related outcomes. The study is nested within a larger program that includes three epidemiological cohort studies of adult drug users and street-involved youth. This approach integrates ethnographic observational fieldwork, in-depth interviews, and geo-spatial mapping techniques with quantitative laboratory and survey data to identify how the social, structural and physical features of drug-use scenes impact HIV outcomes.

Informed by ecological perspectives on health, and the HIV risk environment framework, this study will develop and pilot a novel ethno-spatial approach to identify the complex pathways and dynamics between contextual factors shaping the risk environments of drug use and HIV prevention and treatment for drug users. Building on 10 years of experience studying illicit drug use and HIV/AIDS in the local context, this program of ethno-spatial epidemiology seeks to address the following specific aims:

Examine the influence of evolving social and physical features of “drug scenes” on HIV risk behaviours and HIV incidence among drug users.
Assess the influence of evolving structural and physical factors on critical initiation and transitional events (e.g. initiation into drug use or sex work; transitions in drug use patterns) among drug users and inform epidemiological models of HIV risk.
Examine the impact of evolving structural and physical factors on initiation and adherence to antiretroviral therapy and suppression of HIV-1 RNA among HIV-positive drug users.
Create a platform for the ongoing ethno-spatial evaluation of future public health and public policy interventions targeting drug users.

Operations research applied to assess different strategies to reduce the public health and economic burdens of HIV/AIDS in British Columbia

Although traditional HIV prevention strategies — behaviour modification, condoms, needle exchange – have been very successful, their effect has reached a plateau since they are not always available, practical, or fully adhered to. In the past five years, research has shown that using antiretroviral therapy (ART) to treat those infected with HIV not only decreases mortality and morbidity but also decreases HIV transmission. Unfortunately, many individuals are still unaware that they are HIV-positive or that they should be on ART, since they have not been linked to our health-care system. These individuals will unnecessarily suffer from their disease and they will incur avoidable hospitalizations, physician visits, and costs.

Dr. Viviane Lima aims to identify different strategies to decrease the public health and economic burdens of HIV in British Columbia (BC). Since individuals living with HIV should follow the same continuum of care from infection until the time of first ART, diminishing the individual and economic burdens of HIV will require a combined effort of different players in our health-care system and the development of a comprehensive strategy to tackle each component in the continuum of care pathway. Lima’s research will employ innovative statistical and mathematical models to analyze these data and compare the potential effects of different complex strategies. This project will create great opportunities for trainees to be supported across a variety of disciplines, further enhancing BC’s competitive advantage in population-health and HIV research. The proposed methodology can also be applied to other diseases, conditions, and settings dealing with similar issues.

Health economic evaluation to inform strategies for HIV treatment and prevention

HIV treatment has advanced remarkably since 1996, with the advent of highly active antiretroviral therapy (HAART). HAART stops HIV replication and, as a result, the virus is reduced to undetectable levels. This allows immune reconstitution to take place, leading to long-term disease remission and prolonged survival.

The BC Centre for Excellence in HIV/AIDS (BC-CfE) has demonstrated that HAART renders HIV undetectable in sexual fluids and can dramatically reduce HIV transmission. As a result, the BC-CfE is engaged in a number of HIV “treatment as prevention” initiatives aimed at expanding HIV testing and treatment within BC and internationally to decrease HIV-related morbidity and mortality, as well as HIV transmission.

Dr. Bohdan Nosyk’s research is focused on cost-effectiveness analysis of treatment as prevention strategies to inform the most effective allocation of scarce health resources. The initial objective of this proposal is to construct a mathematical cohort simulation model to determine the cost-effectiveness of HAART scale-up in terms of the total costs accumulated, quality adjusted life years, and HIV incidence in BC from 1996 to 2010. A series of statistical and econometric analyses are required to estimate the relevant clinical and economic parameters needed to populate the simulation model. These analyses will be facilitated by the availability of linked administrative datasets and prospectively collected longitudinal data of HAART utilization, duration, and health outcomes at the population level in BC. The analyses will be stratified by HIV acquisition risk factor. This model will be used to predict the potential impact and cost-effectiveness of future policy changes in BC and internationally.

Impact of structural and environmental factors on risk for HIV/sexually transmitted infections and barriers to accessing prevention, treatment and care among women involved in sex work

Sex workers in Vancouver have been found to be highly vulnerable to a variety of negative health and safety outcomes, including high rates of occupational and historical violence, a high prevalence of HIV (approximately 25 percent within street-based sex workers in Vancouver), and limited access and use of health services. In order to mitigate some of the HIV and sexually transmitted infection (STI) risk in this population, researchers at the Gender and Sexual Health Initiative at the BC Centre for Excellence in HIV/AIDS are looking into understanding some of the larger structural and environmental determinants of HIV/STI risk. Dr. Kathleen Deering is studying a sample of sex workers in Metropolitan Vancouver to investigate the intersecting relationships between different social, environmental and structural factors, such as the availability and access to health services, neighbourhood of residence, and locations and venues of sex work. She will be measuring health and safety outcomes of these women (such as HIV/STI risks, including inconsistent condom use, number of sex partners and sex partnering patterns, and occupational and intimate partner violence) and the geographic distribution of these outcomes over time. This project will access data from a five-year longitudinal cohort of women in sex work in Vancouver, including 500 women and 250 youth sex workers who are 14 to 24 years of age. Participants will fill out a detailed survey and be asked to provide blood and urine samples for HIV and STI testing at the start and every six months for the five-year duration of the study. Dr. Deering will be using these data, combined with social epidemiology methods and Geographic Information Systems (GIS) mapping technology to help understand how social, structural and environmental factors impact risk patterns for HIV/STI and health services use and access. She will also be exploring the use of complex adaptive systems approaches as a novel and key methodological/analytical approach for examining multiple intersecting levels of risk. The results of this research will lead to important recommendations relating to changes in public health policy and the development of effective safer-environment interventions to improve the health and safety of women in sex work in Canadian settings. Results will be communicated to community members, the local and provincial government, and the study population through ongoing partnerships.

Towards evidence-based public health for sex workers in British Columbia

Youth and women working in Vancouver’s sex industry are among the most marginalized and vulnerable in Canadian society. The persistently high rates of health-related issues, violence, and mortality among sex workers, both in Canada and globally, highlights a desperate need for renewed public health interventions targeting the reduction of harms in this industry. Dr. Kate Shannon is working to investigate the different factors influencing the health and safety of youth and women working in the sex industry in Vancouver. Her team is studying the social (violence, work conditions) and structural (laws, regulations, urban renewal) contexts of sexually transmitted infection (STI) in this population. Specifically, her team is examining the different factors that influence the worker’s negotiating power during transactions and how this influences the risk of HIV/STI acquisition. Her research will involve the study and long-term follow-up of two groups of women: (1) 500 existing and new adult women working in both the street and indoor sex industry; and (2) 250 female youth aged 14 to 20 years who have exchanged sex for money, drugs, gifts, shelter, or other commodities in the previous 30 days. By evaluating and integrating different types of data, including individual mapping and neighborhood environment data (including violence and housing) from publicly available sources, she hopes to identify policies and harm-reducing interventions for this population. This study is among the first prospective studies of sex work in North America. Dr. Shannon’s team possesses a wealth of expertise in observational and intervention research, policy, and sex work. They are uniquely positioned to conduct this study, which aims to directly improve the health of some of the most marginalized youth and women in Canadian society.

Investigating clinical outcomes from highly active antiretroviral therapy (HAART) among HIV-seropositive Aboriginal people in British Columbia

The development of effective HIV/AIDS treatment has resulted in dramatic improvements in the health of people infected with the virus. Taken regularly, highly active antiretroviral therapy (HAART) interrupts the viral life cycle, suppresses the level of HIV in a patient's bloodstream, and promotes health improvements. The recent finding that individuals undergoing effective treatment are far less likely to transmit the virus to others has spurred the development of a new strategy aimed at preventing new HIV infections. Dubbed "Seek, Test and Treat", the goal of this initiative is to increase the number of people on HIV treatment in Prince George and in Vancouver's Downtown Eastside.

Dr. M-J Milloy is specifically focusing on the expansion of HIV treatment among people of Aboriginal ancestry who use illicit drugs. In Canada, young Aboriginal people are a growing sector of the HIV/AIDS pandemic, and Aboriginal people are highly over-represented among HIV-positive drug users. Dr. Milloy’s research will look at treatment for HIV and health outcomes for Aboriginal drug users and, in light of increasing calls by Aboriginal leaders for research that focuses on health and wellness among Aboriginal people, will try to identify the characteristics of successful treatment.

Dr. Milloy's research will address a number of outstanding concerns:

Are Aboriginal individuals who are HIV-positive and use illicit drugs being effectively treated with HAART?
What are some of the broader factors, such as stable housing or employment, that promote effective treatment?
What is the level of viral resistance to HIV medications among Aboriginal drug users?

Much of the data for this study will come from the AIDS Care Cohort to Evaluate access to Survival Services, an ongoing study of approximately 750 HIV-positive drug users in Vancouver. The research will be supervised by Dr. Evan Adams, Physician Advisor to the First Nations Health Council, who will ensure that the research is respectful and responsible to Aboriginal participants and communities.

The information gained could be used to improve existing systems to provide HAART as well as inform new Aboriginal-led efforts to improve health and wellness. By improving HAART delivery and expanding the number of people receiving effective care for HIV infection, it is hoped that the number of new infections will also drop.

Place and experiences of risk among young drug users in downtown Vancouver

Illicit drug use is associated with severe harms and immense social suffering among youth. Previous ethnographic work has shown how social-structural and cultural processes present within specific urban locales intersect to push young people who engage in drug use towards ‘risk’, until it becomes difficult or impossible for them to avoid transitioning into increasingly ‘risky’ behaviours. However, there have been relatively few in-depth investigations of drug-using contexts or ‘scenes’ that focus exclusively on the meanings, understandings and everyday lived experiences of young drug users themselves. Danya Fast’s research explores young people’s understandings of the social-structural and physical landscapes of the downtown Vancouver drug scene, and how various locales (e.g. neighbourhoods, alleyways, service locations, residences), shape experiences of ‘safety’ and ‘risk’ among drug-using youth. Her approach emphasizes the influence of place on health, where place is understood to encompass both physical and social spaces. An important goal of this research will be the identification of elements in the physical and social environment that shape risk and structural interventions that alter context and, by consequence, facilitate safer spaces for work, rest and recreation for youth. Ms. Fast’s project will result in a more comprehensive and culturally sensitive account of young drug users’ everyday experiences in the context of the downtown Vancouver drug scene, and will also be used to inform ongoing epidemiological research with drug-using youth. Moreover, Ms. Fast’s project will contribute to the development of an ongoing ethno-epidemiological research program that has been identified as an important emergent area within Human Immunodeficiency Virus research, due to its unique ability to inform the development of interventions designed to reduce drug-related harms.

An ethno-epidemiological investigation of social and environmental contexts of HIV vulnerability among injection drug users

Outside of Africa, an estimated two-thirds of new Human Immunodeficiency virus (HIV), infections are believed to occur among people who inject illicit drugs. While an urgent need exists for tailored interventions to address HIV risk behaviour within vulnerable groups such as adult injection drug users (IDU), there are major knowledge gaps that must first be addressed if interventions are to be successful. Innovative approaches to examine how participation in particular social contexts and environments foster vulnerability to HIV are crucial to the development of effective intervention strategies among highly vulnerable populations of IDUs. William Small is conducting research to address this need using ethnographic methods to develop empirical information regarding transitions into particular high-risk social contexts, including drug markets and sex trade activities. Specifically, his research focuses on the risk environments in two different geographical settings, Vancouver, Canada and Sydney, Australia. The results will provide critical insight regarding how participation in these high-risk settings influences HIV risks as well as an individual’s ability to engage in risk reduction in the context of injection drug use. The information will be integrated with findings from ongoing epidemiological studies in the same locales to test socially-oriented hypotheses regarding the relationship between HIV vulnerabilities and particular social contexts. Ultimately, the findings from Mr. Smalls’ research will help advance the study of HIV risks among IDUs, and inform the development of social and community interventions designed to reduce HIV transmission.