Examining the secondary impacts of the COVID-19 pandemic on syndemic production and PrEP use among gay, bisexual and other men who have sex with men (GBM) in Vancouver, Canada.

BACKGROUND: The secondary impacts of the COVID-19 pandemic may disproportionately affect gay, bisexual, and other men who have sex with men (GBM), particularly related to HIV prevention and treatment outcomes. We applied syndemic theory to examine PrEP disruptions during the during the height of the COVID-19 pandemic in Vancouver, Canada. METHODS: Sexually-active GBM, aged 16 + years, were enrolled through respondent-driven sampling (RDS) from February 2017 to August 2019. Participants completed a Computer-Assisted Self-Interview every six months and data were linked to the BC PrEP Program (program responsible for publicly funded PrEP in the province) to directly measure PrEP disruptions. The analysis period for this study was from March 2018-April 2021. We used univariable generalized linear mixed models to examine (1) six-month trends for syndemic conditions: the prevalence of moderate/severe depressive or anxiety symptoms, polysubstance use, harmful alcohol consumption, intimate partner violence, and (2) six-month trends for PrEP interruptions among HIV-negative/unknown GBM. We also applied 3-level mixed-effects logistic regression with RDS clustering to examine whether syndemic factors were associated with PrEP interruptions. RESULTS: Our study included 766 participants, with 593 participants who had at least one follow-up visit. The proportion of respondents with abnormal depressive symptoms increased over the study period (OR = 1.35; 95%CI = 1.17, 1.56), but we found decreased prevalence for polysubstance use (OR = 0.89; 95%CI = 0.82, 0.97) and binge drinking (OR = 0.74; 95%CI = 0.67, 0.81). We also found an increase in PrEP interruptions (OR = 2.33; 95%CI = 1.85, 2.94). GBM with moderate/severe depressive symptoms had higher odds (aOR = 4.80; 95%CI = 1.43, 16.16) of PrEP interruptions, while GBM with experiences of IPV had lower odds (aOR = 0.38; 95%CI = 0.15, 0.95) of PrEP interruptions. GBM who met clinical eligibility for PrEP had lower odds of experiencing PrEP interruptions (aOR = 0.25; 95%CI = 0.11, 0.60). CONCLUSION: There were increasing PrEP interruptions since March 2020. However, those most at risk for HIV were less likely to have interruptions. Additional mental health services and targeted follow-up for PrEP continuation may help to mitigate the impacts of the COVID-19 pandemic on GBM.

Reduced Magnitude and Durability of Humoral Immune Responses to COVID-19 mRNA Vaccines Among Older Adults.

BACKGROUND: The magnitude and durability of immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines remain incompletely characterized in the elderly. METHODS: Anti-spike receptor-binding domain (RBD) antibodies, angiotensin-converting enzyme 2 (ACE2) competition, and virus neutralizing activities were assessed in plasma from 151 health care workers and older adults (range, 24-98 years of age) 1 month following the first vaccine dose, and 1 and 3 months following the second dose. RESULTS: Older adults exhibited significantly weaker responses than younger health care workers for all humoral measures evaluated and at all time points tested, except for ACE2 competition activity after 1 vaccine dose. Moreover, older age remained independently associated with weaker responses even after correction for sociodemographic factors, chronic health condition burden, and vaccine-related variables. By 3 months after the second dose, all humoral responses had declined significantly in all participants, and remained significantly lower among older adults, who also displayed reduced binding antibodies and ACE2 competition activity towards the Delta variant. CONCLUSIONS: Humoral responses to COVID-19 mRNA vaccines are significantly weaker in older adults, and antibody-mediated activities in plasma decline universally over time. Older adults may thus remain at elevated risk of infection despite vaccination.

Older Adults Mount Less Durable Humoral Responses to Two Doses of COVID-19 mRNA Vaccine but Strong Initial Responses to a Third Dose.

BACKGROUND: Third coronavirus disease 2019 (COVID-19) vaccine doses are broadly recommended, but immunogenicity data remain limited, particularly in older adults. METHODS: We measured circulating antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, ACE2 displacement, and virus neutralization against ancestral and omicron (BA.1) strains from prevaccine up to 1 month following the third dose, in 151 adults aged 24-98 years who received COVID-19 mRNA vaccines. RESULTS: Following 2 vaccine doses, humoral immunity was weaker, less functional, and less durable in older adults, where a higher number of chronic health conditions was a key correlate of weaker responses and poorer durability. One month after the third dose, antibody concentrations and function exceeded post-second-dose levels, and responses in older adults were comparable in magnitude to those in younger adults at this time. Humoral responses against omicron were universally weaker than against the ancestral strain after both the second and third doses. Nevertheless, after 3 doses, anti-omicron responses in older adults reached equivalence to those in younger adults. One month after 3 vaccine doses, the number of chronic health conditions, but not age, was the strongest consistent correlate of weaker humoral responses. CONCLUSIONS: Results underscore the immune benefits of third COVID-19 vaccine doses, particularly in older adults.

Crystal Methamphetamine Use and Initiation among Gay, Bisexual, and Other Men Who Have Sex with Men Living with HIV in a Treatment as Prevention Environment.

BACKGROUND: Risk compensation in an HIV Treatment as Prevention (TasP) environment may increase high-risk sexual and substance use behaviors among people living with HIV. Objective: To examine recent crystal methamphetamine (CM) use/initiation in a longitudinal cohort of gay, bisexual, and other men who have sex with men (GBMSM) living with HIV in Metro Vancouver, Canada. Methods: Eligible participants were GBMSM aged >15 years who reported sex with another man in the past six months. Participants were recruited using respondent-driven sampling and self-completed a computer questionnaire every six months. We used multi-level generalized mixed-effect models to evaluate trends in recent CM use (past six months), multivariable logistic regression to identify covariates of recent CM use, and multivariable survival analysis to identify predictors of CM initiation. Results: Of 207 GBMSM living with HIV at enrollment, 44.3% reported recent CM use; there was a statistically non-significant decrease over the study period (41% in first period to 25% in final period, p = 0.087). HIV treatment optimism was not associated with CM use/initiation. CM use was positively associated with depressive symptomology, sexual escape motivation, transactional sex, number of anal sex partners, condomless anal sex with seroconcordant partners, STIs, and other substance use. Recent CM use was negatively associated with viral load sorting. CM initiation was predicted by escape motivation, transactional sex, and group sex participation. Conclusion: Results suggest that CM use among GBMSM living with HIV is prevalent and increased CM use/initiation is not a consequence of TasP public policy.

Protocol of the impact of alternative social assistance disbursement on drug-related harm (TASA) study: a randomized controlled trial to evaluate changes to payment timing and frequency among people who use illicit drugs.

BACKGROUND: Government social assistance payments seek to alleviate poverty and address survival needs, but their monthly disbursement may cue increases in illicit drug use. This cue may be magnified when assistance is disbursed simultaneously across the population. Synchronized payments have been linked to escalations in drug use and unintended but severe drug-related harms, including overdose, as well as spikes in demand for health, social, financial and police services. METHODS/DESIGN: The TASA study examines whether changing payment timing and frequency can mitigate drug-related harm associated with synchronized social assistance disbursement. The study is a parallel arm multi-group randomized controlled trial in which 273 participants are randomly allocated for six assistance cycles to a control or one of two intervention arms on a 1:1:1 basis. Intervention arm participants receive their payments: (1) monthly; or (2) semi-monthly, in each case on days that are not during the week when cheques are normally issued. The study partners with a community-based credit union that has developed a system to vary social assistance payment timing. The primary outcome is a 40 % increase in drug use during the 3 days beginning with cheque issue day compared to other days of the month. Bi-weekly follow-up interviews collect participant information on this and secondary outcomes of interest, including drug-related harm (e.g. non-fatal overdose), exposure to violence and health service utilization. Self-reported data will be supplemented with participant information from health, financial, police and government administrative databases. A longitudinal, nested, qualitative parallel process evaluation explores participant experiences, and a cost-effectiveness evaluation of different disbursement scenarios will be undertaken. Outcomes will be compared between control and intervention arms to identify the impacts of alternative disbursement schedules on drug-related harm resulting from synchronized income assistance. DISCUSSION: This structural RCT benefits from strong community partnerships, highly detailed outcome measurement, robust methods of randomization and data triangulation with third party administrative databases. The study will provide evidence regarding the potential importance of social assistance program design as a lever to support population health outcomes and service provision for populations with a high prevalence of substance use. TRIAL REGISTRATION: NCT02457949 Registered 13 May 2015.

Optimizing an HIV testing program using a system dynamics model of the continuum of care.

Realizing the full individual and population-wide benefits of antiretroviral therapy for human immunodeficiency virus (HIV) infection requires an efficient mechanism of HIV-related health service delivery. We developed a system dynamics model of the continuum of HIV care in Vancouver, Canada, which reflects key activities and decisions in the delivery of antiretroviral therapy, including HIV testing, linkage to care, and long-term retention in care and treatment. To measure the influence of operational interventions on population health outcomes, we incorporated an HIV transmission component into the model. We determined optimal resource allocations among targeted and routine testing programs to minimize new HIV infections over five years in Vancouver. Simulation scenarios assumed various constraints informed by the local health policy. The project was conducted in close collaboration with the local health care providers, Vancouver Coastal Health Authority and Providence Health Care.

Continuing professional development in HIV chronic disease management for primary care providers.

Primary care providers need continuing professional development (CPD) in order to improve their knowledge and confidence in the care of patients with chronic conditions. We developed an intensive modular CPD program in the chronic disease management of HIV for primary care providers. The program combines self-directed learning, interactive tutorials with experts, small group discussions, case studies, clinical training, one-on-one mentoring and individualized learning objectives. We trained 27 family physicians and 7 nurse practitioners between 2011 and 2013. The trainees reported high levels of satisfaction with the program. There was a 136.76% increase in the number of distinct HIV-positive patients receiving HIV-related medication refills that were prescribed by the trainees.

Controlling the HIV epidemic with antiretrovirals: moving from consensus to implementation.

The second Controlling the HIV With Antiretrovirals evidence summit was held 22-24 September 2013, in London, England. This preface summarizes the summit's background and key themes, and is an introduction to a series of articles written by select summit faculty and featured in this supplement. In many respects, the supplement can serve as a roadmap for how to move from general consensus around to wider scale implementation of a comprehensive menu of interventions to control the HIV epidemic.

Leveraging HIV treatment to end AIDS, stop new HIV infections, and avoid the cost of inaction.

We have the tools at our disposal to significantly bend AIDS-related morbidity and mortality curves and reduce human immunodeficiency virus (HIV) incidence. It is thus essential to redouble our efforts to reach the goal of placing 15 million people on life-saving and -enhancing antiretroviral therapy (ART) by 2015. In reaching this milestone, we can write a new chapter in the history of global health, demonstrating that a robust, multidimensional response can succeed against a complex pandemic that presents as many social and political challenges as it does medical ones. This milestone is also critical to advance our ultimate goal of ending AIDS by maximizing the therapeutic and preventive effects of ART, which translates into a world in which AIDS-related deaths and new HIV infections are exceedingly rare.

Global response to HIV: treatment as prevention, or treatment for treatment?

The concept of "treatment as prevention" has emerged as a means to curb the global HIV epidemic. There is, however, still ongoing debate about the evidence on when to start antiretroviral therapy in resource-poor settings. Critics have brought forward multiple arguments against a "test and treat" approach, including the potential burden of such a strategy on weak health systems and a presumed lack of scientific support for individual patient benefit of early treatment initiation. In this article, we highlight the societal and individual advantages of treatment as prevention in resource-poor settings. We argue that the available evidence renders the discussion on when to start antiretroviral therapy unnecessary and that, instead, efforts should be aimed at offering treatment as soon as possible.

Incarceration of people living with HIV/AIDS: implications for treatment-as-prevention.

Contact with the criminal justice system, including incarceration, is a common experience for many people living with HIV/AIDS. Optimism has recently been expressed that correctional facilities could be important locations for treatment-as-prevention (TasP)-based initiatives. We review recent findings regarding the effect of incarceration on patterns of HIV transmission, testing, treatment initiation and retention. We found that the prevalence of HIV infection among incarcerated individuals remains higher than analogous non-incarcerated populations. Recent studies have shown that voluntary HIV/AIDS testing is feasible in many correctional facilities, although the number of previously undiagnosed individuals identified has been modest. Studies have implied enhanced linkage to HIV/AIDS treatment and care in jails in the United States was associated with improvements in the HIV cascade of care. However, for many individuals living with HIV/AIDS, exposure to the correctional system remains an important barrier to retention in HIV/AIDS treatment and care. Future research should evaluate structural interventions to address these barriers and facilitate the scale-up of TasP-based efforts among individuals living in correctional settings.

Process description of developing HIV prevention monitoring indicators for a province-wide pre-exposure prophylaxis (PrEP) program in British Columbia, Canada.

In 2018, the pre-exposure prophylaxis (PrEP) program was initiated in British Columbia (BC), Canada, providing PrEP at no cost to qualifying residents. This observational study discussed the steps to develop key evidence-based monitoring indicators and their calculation using real-time data. The indicators were conceptualized, developed, assessed and approved by the Technical Monitoring Committee of representatives from five health authority regions in BC, the BC Ministry of Health, the BC Centre for Disease Control, and the BC Centre for Excellence in HIV/AIDS. Indicator development followed the steps adopted from the United States Centers for Disease Control and Prevention framework for program evaluation in public health. The assessment involved eight selection criteria: data quality, indicator validity, existing scientific evidence, indicator informativeness, indicator computing feasibility, clients' confidentiality maintenance capacity, indicator accuracy, and administrative considerations. Clients' data from the provincial-wide PrEP program (January 2018-December 2020) shows the indicators' calculation. The finalized 14 indicators included gender, age, health authority, new clients enrolled by provider type and by the health authority, new clients dispensed PrEP, clients per provider, key qualifying HIV risk factor(s), client status, PrEP usage type, PrEP quantity dispensed, syphilis and HIV testing and incident cases, and adverse drug reaction events. Cumulative clients' data (n = 6966; 99% cis-gender males) identified an increased new client enrollment and an unexpected drop during the COVID-19 pandemic. About 80% dispensed PrEP from the Vancouver Coastal health authority. The HIV incidence risk index for men who have sex with men score ≥10 was the most common qualifying risk factor. The framework we developed integrating indicators was applied to monitor our PrEP program, which could help reduce the public health impact of HIV.

Sex work and the public health impacts of the 2010 Olympic Games.

OBJECTIVES: The authors examined the impact of exposure to the 2010 Winter Olympics time period on outcomes measuring disruption of local sex work environments in Vancouver, Canada. METHODS: The authors conducted a before-and-after study, using multivariable logistic regression, to assess the relationship between exposure to the Olympics period (19 January-14 March 2010) versus the post-Olympics period (1 April-1 July 2010) and outcomes. RESULTS: This study included 207 youth (14+ years) and adult sex workers (SWs) (Olympics: n=107; post-Olympics: n=100). SWs in the two periods were statistically similar, with an overall median age of 33 years (IQR: 28-40), and 106 (51.2%) of indigenous ancestry or ethnic minority. In separate multivariable logistic regression models, the Olympics period remained statistically significantly associated with perceived heightened police harassment of SWs without arrest (adjusted ORs (AOR): 3.95, 95% CIs 1.92 to 8.14), decreased availability of clients (AOR: 1.97, 95% CIs 1.11 to 3.48) and increased difficulty meeting clients due to road closures/construction (AOR: 7.68, 95% CIs 2.46 to 23.98). There were no significantly increased odds in perceived reports of new (0.999), youth (0.536) or trafficked SWs (zero reports) in the Olympic period. CONCLUSIONS: To reduce potential adverse public health impacts of enhanced police harassment and displacement of local sex work markets, results suggest that evidence-based public health strategies need to be adopted for host cities of future events (eg, the London 2012 Olympic Games), such as the removal of criminal sanctions targeting sex work and the piloting and rigorous evaluation of safer indoor work spaces.

Asking the right questions: developing evidence-based strategies for treating HIV in women and children.

In July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highly active antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults and children, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO's new recommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatment alone will increase the number of treatment-eligible people by 50% or more.Scaling up access to HIV treatment is revealing important gaps in our understanding of how best to provide for all those in need. This knowledge gap is especially significant in developing countries, where women and children comprise a majority of those living with HIV infection. Given the magnitude and significance of these populations, the International AIDS Society, through its Industry Liaison Forum, prioritized HIV treatment and prophylaxis of women and children. In March 2010, the International AIDS Society and 15 partners launched a Consensus Statement outlining priority areas in which a relative lack of knowledge impedes delivery of optimal prevention of mother to child transmission (PMTCT) and treatment to women and children.The Consensus Statement, "Asking the Right Questions: Advancing an HIV Research Agenda for Women and Children", makes a special appeal for a more gender-sensitive approach to HIV research at all stages, from conception to design and implementation. It particularly emphasizes research to enhance the understanding of sex-based differences and paediatric needs in treatment uptake and response. In addition to clinical issues, the statement focuses on programmatic research that facilitates access and adherence to antiretroviral regimens. Better coordination of HIV management with sexual and reproductive healthcare delivery is one such approach.We discuss here our knowledge gaps concerning effective, safe PMTCT and treatment for women and children in light of the expansion envisioned by WHO's revised guidelines. The guideline's new goals present an opportunity for advancing the women and children's agenda outlined in the Consensus Statement.

Can the combination of TasP and PrEP eliminate HIV among MSM in British Columbia, Canada?

INTRODUCTION: In British Columbia (BC), the HIV epidemic continues to disproportionally affect the gay, bisexual and other men who have sex with men (MSM). In this study, we aimed to evaluate how Treatment as Prevention (TasP) and pre-exposure prophylaxis (PrEP), if used in combination, could lead to HIV elimination in BC among MSM. METHODS: Considering the heterogeneity in HIV transmission risk, we developed a compartmental model stratified by age and risk-taking behaviour for the HIV epidemic among MSM in BC, informed by clinical, behavioural and epidemiological data. Key outcome measures included the World Health Organization (WHO) threshold for disease elimination as a public health concern and the effective reproduction number (Re). Model interventions focused on the optimization of different TasP and PrEP components. Sensitivity analysis was done to evaluate the impact of sexual mixing patterns, PrEP effectiveness and increasing risk-taking behaviour. RESULTS: The incidence rate was estimated to be 1.2 (0.9-1.9) per 1000 susceptible MSM under the Status Quo scenario by the end of 2029. Optimizing all aspects of TasP and the simultaneous provision of PrEP to high-risk MSM resulted in an HIV incidence rate as low as 0.4 (0.3-0.6) per 1000 susceptible MSM, and an Re as low as 0.7 (0.6-0.9), indicating that disease elimination was possible when TasP and PrEP were combined. Provision of PrEP to younger MSM or high-risk and younger MSM resulted in a similar HIV incidence rate, but an Re with credible intervals that crossed one. CONCLUSION: Further optimizing all aspects of TasP and prioritizing PrEP to high-risk MSM can achieve the goal of disease elimination in BC. These results should inform public health policy development and intervention programs that address the HIV epidemic in BC and in other similar settings where MSM are disproportionately affected.

Chronic Hepatitis B Infection Among Preexposure Prophylaxis Users Enrolled in a Population-Based Program in British Columbia, Canada.

Initiation of human immunodeficiency virus preexposure prophylaxis (PrEP) medications will also treat hepatitis B infection (HBV). The prevalence of chronic HBV was 0.86% (n=41/4760) among enrollees in a provincial PrEP program in British Columbia, Canada. Overall, 46.3% lacked follow-up HBV DNA monitoring, underscoring the need for HBV-related education for PrEP prescribers.

Developing Canada's research base for harm reduction and health equity approaches to HIV prevention and treatment.

In the area of infectious disease control, Canadian research efforts to address the HIV epidemic in Vancouver's Downtown East Side neighbourhood have fueled the development of harm reduction and health equity perspectives worldwide. These research efforts have, in turn, reshaped the field of public health approaches to HIV prevention and control. As a result of the intensive and sustained research initiatives led by Canadian scientists Drs. Thomas Kerr and Evan Wood, the 'HIV problem' and public health responses to it have been radically reconceptualized - shifting from an exclusive focus on individual choice towards asking fundamental questions about our society and the structural features that put people at risk for contracting HIV. Their research on harm reduction and health equity related to HIV vulnerability and outcomes has informed and shaped: (1) the establishment of North America's first supervised injection facility, Insite, located in Vancouver's Downtown East Side neighbourhood; (2) dramatic changes to Vancouver's needle exchange policies; (3) HIV treatment approaches among injection drug using populations (IDU). By drawing attention to the ways in which Canadian health care policies and programs can be restructured to better support the health of vulnerable populations, the work of Drs. Kerr and Wood represents a uniquely Canadian public health milestone.