Healthcare utilisation and costs associated with adherence to antipsychotics among people living with HIV/AIDS and schizophrenia: a population-based cohort study in British Columbia, Canada.

OBJECTIVES: Non-adherence to antipsychotics is the greatest obstacle to treating schizophrenia. We assessed the economic and clinical impacts of adherence to antipsychotics among people living with HIV/AIDS (PLWH) and schizophrenia in British Columbia, Canada. DESIGN AND SETTING: A population-based cohort study in British Columbia, Canada. METHODS: Eligible PLWH were enrolled in the Seek and Treat for Optimal Prevention HIV/AIDS population-based cohort during 2001-2016, diagnosed with schizophrenia, on antipsychotics for ≥1 day, and followed for ≥1 year from schizophrenia diagnosis date or 1 January 2001, whichever occurred last. PRIMARY AND SECONDARY OUTCOME MEASURES: A two-part model assessed the marginal effect of adherence on healthcare costs (in 2016 Canadian dollar), while logistic regression examined the effect on virological failure, and generalised linear mixed models examined the effect on hospital readmissions within 30 days and length of hospital stay. RESULTS: Among 726 PLWH with schizophrenia, ≥80% adherence to antipsychotics increased from 25% (50/198) in 2001 to 41% (225/554) in 2016. In most years, we observed no difference in adherence to antipsychotics among those who used only injectables, only non-injectables, and a combination of both, or among those who have ever consumed typical/first-generation antipsychotics and who consumed only atypical/second-generation antipsychotics. Overall healthcare costs were higher in the non-adherent group ($C2185), driven by the average annual hospitalisation costs ($C5517), particularly among women ($C8806) and people who ever injected drugs (PWID) ($C5985). Non-adherent individuals also experienced higher hospital readmissions (adjusted odds ratio (aOR) 1.48, 95% CI 1.23 to 1.77), and longer hospital stays (adjusted mean ratio 1.23, 95% CI 1.13 to 1.35) in comparison to adherent individuals. We found no difference in virological failure by adherence groups, except when we stratified by gender where the aOR for women was 2.48 (95% CI 1.06 to 5.82). CONCLUSIONS: Our results showed that implementing strategies and interventions to increase antipsychotic adherence, particularly among women and PWID, will be critical in addressing this public health challenge.

Detection of HIV transmission hotspots in British Columbia, Canada: A novel framework for the prioritization and allocation of treatment and prevention resources.

BACKGROUND: Identifying populations at high risk of HIV transmission is critical for prioritizing treatment and prevention resources and achieving the UNAIDS 90-90-90 Targets. METHODS: HIV transmission rates can be estimated from phylogenetic trees as viral lineage-level diversification rates. To identify HIV-1 transmission foci in British Columbia, Canada, we inferred diversification rates from phylogenetic trees of 36 271 HIV-1 sequences from 9630 anonymized individuals. Diversification rates were combined with sociodemographic and clinical data, then aggregated by patients' area of residence to predict the distribution of new HIV cases between 2008 and 2018. The predictive power of the model was compared with a phylogenetically uninformed model. FINDINGS: Aggregated diversification rate measures were predictive of new HIV cases in the subsequent year after adjusting for prevalent and incident cases in the previous year. For every one-unit increase in the mean of the top five diversification rates, the number of new HIV cases increased by on average 1·38-fold (95% CI, 1·28-1·49). In a blind prediction of 2018 cases, diversification rate improved the model's specificity by 12%, accuracy by 9%, top 20 agreement by 100%, and correlation of predicted and observed values by 162% relative to a model that incorporated epidemiological data alone. INTERPRETATION: By predicting the distribution of future HIV cases, a combined phylogenetic and epidemiological approach identifies hotspots where public health resources are needed most. FUNDING: Canadian Institutes of Health Research, University of British Columbia, Public Health Agency of Canada, Genome Canada, Genome BC, Michael Smith Foundation for Health Research, and BC Centre for Excellence in HIV/AIDS.

Geographic variation in the costs of medical care for people living with HIV in British Columbia, Canada.

BACKGROUND: Regional variation in medical care costs can indicate heterogeneity in clinical practice, inequities in access, or inefficiencies in service delivery. We aimed to estimate regional variation in medical costs for people living with HIV (PLHIV), adjusting for demographics and case-mix. METHODS: We conducted a retrospective cohort study using linked health administrative databases of PLHIV, from 2010 to 2014, in British Columbia (BC), Canada. Quarterly health care costs (2018 CAD) were derived from inpatient, outpatient, prescription drugs, antiretroviral therapy (ART), and HIV diagnostics. We used a two-part model with a logit link for the probability of incurring costs, and a log link and gamma distribution for observations with positive costs. We also estimated quarterly utilization rates for hospitalization-, physician billing- and prescription drug-days. Primary variables were indicators of individuals' Health Service Delivery Area (HSDA). We adjusted cost and utilization estimates for demographic characteristics, HIV-disease progression, and comorbidities. RESULTS: Our cohort included 9577 PLHIV (median age 45.5 years, 80% male). Adjusted total quarterly costs for all 16 HSDAs were within 20% of the provincial mean, 8/16 for hospitalization costs, 16/16 for physician billing costs and 10/16 for prescription drug costs. Northern Interior and Northeast HSDAs had 38 and 44% lower quarterly non-ART prescription drug costs, and 2 and 5% higher quarterly inpatient costs, respectively. CONCLUSIONS: We observed limited variation in medical care costs and utilization among PLHIV in BC. However, lower levels of outpatient care and higher levels of inpatient care indicate possible barriers to accessing care among PLHIV in the most rural regions of the province.

Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

Born out of a necessity for fiscal sustainability, simulation modeling is playing an increasingly prominent role in setting priorities for combination implementation strategies for HIV treatment and prevention globally. The design of a model and the data inputted into it are central factors in ensuring credible inferences. We executed a narrative review of a set of dynamic HIV transmission models to comprehensively synthesize and compare the structural design and the quality of evidence used to support each model. We included 19 models representing both generalized and concentrated epidemics, classified as compartmental, agent-based, individual-based microsimulation or hybrid in our review. We focused on four structural components (population construction; model entry, exit and HIV care engagement; HIV disease progression; and the force of HIV infection), and two analytical components (model calibration/validation; and health economic evaluation, including uncertainty analysis). While the models we reviewed focused on a variety of individual interventions and their combinations, their structural designs were relatively homogenous across three of the four focal components, with key structural elements influenced by model type and epidemiological context. In contrast, model entry, exit and HIV care engagement tended to differ most across models, with some health system interactions-particularly HIV testing-not modeled explicitly in many contexts. The quality of data used in the models and the transparency with which the data was presented differed substantially across model components. Representative and high-quality data on health service delivery were most commonly not accessed or were unavailable. The structure of an HIV model should ideally fit its epidemiological context and be able to capture all efficacious treatment and prevention services relevant to a robust combination implementation strategy. Developing standardized guidelines on evidence syntheses for health economic evaluation would improve transparency and help prioritize data collection to reduce decision uncertainty.

Why Maximizing Quality-Adjusted Life Years, rather than Reducing HIV Incidence, Must Remain Our Objective in Addressing the HIV/AIDS Epidemic.

With efficacious behavioral, biomedical, and structural interventions available, combination implementation strategies are being implemented to combat HIV/AIDS across settings internationally. However, priority statements from national and international bodies make it unclear whether the objective should be the reduction in HIV incidence or the maximization of health, most commonly measured with quality-adjusted life years (QALYs). Building off a model-based evaluation of HIV care interventions in British Columbia, Canada, we compare the optimal sets of interventions that would be identified using HIV infections averted, and QALYs as the primary outcome in a cost-effectiveness analysis. We found an explicit focus on averting new infections undervalues the health benefits derived from antiretroviral therapy, resulting in suboptimal and potentially harmful funding recommendations.

The impact of HCV co-infection status on healthcare-related utilization among people living with HIV in British Columbia, Canada: a retrospective cohort study.

BACKGROUND: The burden of HCV among those living with HIV remains a major public health challenge. We aimed to characterize trends in healthcare-related visits (HRV) of people living with HIV (PLW-HIV) and those living with HIV and HCV (PLW-HIV/HCV), in British Columbia (BC), and to identify risk factors associated with the highest HRV rates over time. METHODS: Eligible individuals, recruited from the BC Seek and Treat for Optimal Prevention of HIV/AIDS population-based retrospective cohort (N = 3955), were ≥ 18 years old, first started combination antiretroviral therapy (ART) between 01/01/2000-31/12/2013, and were followed for ≥6 months until 31/12/2014. The main outcome was HRV rate. The main exposure was HIV/HCV co-infection status. We built a confounder non-linear mixed effects model, adjusting for several demographic and time-dependent factors. RESULTS: HRV rates have decreased since 2000 in both groups. The overall age-sex standardized HRV rate (per person-year) among PLW-HIV and PLW-HIV/HCV was 21.11 (95% CI 20.96-21.25) and 41.69 (95% CI 41.51-41.88), respectively. The excess in HRV in the co-infected group was associated with late presentation for ART, history of injection drug use, sub-optimal ART adherence and a higher number of comorbidities. The adjusted HRV rate ratio for PLW-HIV/HCV in comparison to PLW-HIV was 1.18 (95% CI 1.13-1.24). CONCLUSIONS: Although HRV rates have decreased over time in both groups, PLW-HIV/HCV had 18% higher HRV than those only living with HIV. Our results highlight several modifiable risk factors that could be targeted as potential means to minimize the disease burden of this population and of the healthcare system.

Cohort profile: the Comparative Outcomes And Service Utilization Trends (COAST) Study among people living with and without HIV in British Columbia, Canada.

PURPOSE: The Comparative Outcomes And Service Utilization Trends (COAST) Study in British Columbia (BC), Canada, was designed to evaluate the determinants of health outcomes and health care services use among people living with HIV (PLHIV) as they age in the period following the introduction of combination antiretroviral therapy (cART). The study also assesses how age-associated comorbidities and health care use among PLHIV may differ from those observed in the general population. PARTICIPANTS: COAST was established through a data linkage between two provincial data sources: The BC Centre for Excellence in HIV/AIDS Drug Treatment Program, which centrally manages cART dispensation across BC and contains prospectively collected data on demographic, immunological, virological, cART use and other clinical information for all known PLHIV in BC; and Population Data BC, a provincial data repository that holds individual event-level, longitudinal data for all 4.6 million BC residents. COAST participants include 13 907 HIV-positive adults (≥19 years of age) and a 10% random sample inclusive of 516 340 adults from the general population followed from 1996 to 2013. FINDINGS TO DATE: For all participants, linked individual-level data include information on demographics, health service use (eg, inpatient care, outpatient care and prescription medication dispensations), mortality, and HIV diagnostic and clinical data. Publications from COAST have demonstrated the significant mortality reductions and dramatic changes in the causes of death among PLHIV from 1996 to 2012, differences in the amount of time spent in a healthy state by HIV status, and high levels of injury and mood disorder diagnosis among PLHIV compared with the general population. FUTURE PLANS: To capture the dynamic nature of population health parameters, regular data updates and a refresh of the data linkage are planned to occur every 2 years, providing the basis for planned analysis to examine age-associated comorbidities and patterns of health service use over time.

Informing Targeted Interventions to Optimize the Cascade of HIV Care Using Cluster Analyses of Health Resource Use Among People Living with HIV/AIDS.

Increased awareness of the secondary preventive benefits of antiretroviral treatment (ART) has strengthened the desire to optimize health care systems' response to HIV/AIDS. We identified clusters of health resource utilization (HRU) among people living with HIV (PLHIV) to inform targeted interventions aimed to optimize the cascade of HIV care. Using linked population-level health databases in British Columbia, Canada, we selected two analytic samples of PLHIV with 3 years of follow-up between 2006-2011 that were classified as intermittently retained in care or intermittently engaged in ART, and executed a probabilistic model-based clustering analysis for each sample with 5 and 9 quarterly HRU variables, respectively. We found clear HRU profile differences among both samples with similar HIV-related care: one featured active involvement in non-HIV care, the other little or no health care interaction following linkage to care. Differential reengagement intervention strategies capitalizing on missed opportunities in non-HIV care and further engaging physicians delivering HIV care are needed to optimize the response to the HIV epidemic.

The Cost-Effectiveness of Human Immunodeficiency Virus Testing and Treatment Engagement Initiatives in British Columbia, Canada: 2011-2013.

Background: Recognition of the secondary preventive benefits of antiretroviral therapy (ART) has mobilized global efforts to "seek, test, treat, and retain" people living with human immunodeficiency virus [HIV]/AIDS (PLHIV) in HIV care. We aimed to determine the cost-effectiveness of a set of HIV testing and treatment engagement interventions initiated in British Columbia, Canada, in 2011-2013. Methods: Using a previously validated dynamic HIV transmission model, linked individual-level health administrative data for PLHIV, and aggregate-level HIV testing data, we estimated the cost-effectiveness of primary care testing (hospital, emergency department [ED], outpatient), ART initiation, and ART retention initiatives vs a counterfactual scenario that approximated the status quo. HIV incidence, mortality, costs (in 2015$CDN), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios were estimated. Analyses were executed over 5- to 25-year time horizons from a government-payer perspective. Results: ED testing was the best value at $30216 per QALY gained and had the greatest impact on incidence and mortality among PLHIV, while ART initiation provided the greatest QALY gains. The ART retention initiative was not cost-effective. Delivered in combination at the observed scale and sustained throughout the study period, we estimated a 12.8% reduction in cumulative HIV incidence and a 4.7% reduction in deaths among PLHIV at $55258 per QALY gained. Results were most sensitive to uncertainty in the number of undiagnosed PLHIV. Conclusions: HIV testing and ART initiation interventions were cost-effective, while the ART retention intervention was not. Developing strategies to reengage PLHIV lost to care is a priority moving forward.

Increased mortality among Indigenous persons in a multisite cohort of people living with HIV in Canada.

OBJECTIVE: Compare all-cause mortality between Indigenous participants and participants of other ethnicities living with HIV initiating combination antiretroviral therapy (cART) in an interprovincial multi-site cohort. METHODS: The Canadian Observational Cohort is a collaboration of 8 cohorts of treatment-naïve persons with HIV initiating cART after January 1, 2000. Participants were followed from the cART initiation date until death or last viral load (VL) test date on or before December 31, 2012. Cox proportional hazard models were used to estimate the effect of ethnicity on time until death after adjusting for age, gender, injection drug use, being a man who has sex with men, hepatitis C, province of origin, baseline VL and CD4 count, year of cART initiation and class of antiretroviral medication. RESULTS: The study sample consisted of 7080 participants (497 Indigenous, 2471 Caucasian, 787 African/Caribbean/Black (ACB), 629 other, and 2696 unknown ethnicity). Most Indigenous persons were from British Columbia (BC) (83%), with smaller numbers from Ontario (13%) and Québec (4%). During the study period, 714 (10%) participants died. The five-year survival probability was lower for Indigenous persons (0.77) than for Caucasian (0.94), ACB (0.98), other ethnicities (0.96) and unknown ethnicities (0.85) (p < 0.0001). In an adjusted proportional hazard model for which missing data were imputed, Indigenous persons were more likely to die than Caucasian participants (hazard ratio = 2.69, p < 0.0001). CONCLUSION: The mortality rate for Indigenous persons was higher than for other ethnicities and is largely reflective of the BC population. Addressing treatment challenges and identifying HIV- and non-HIV-related causes for mortality among Indigenous persons is required to optimize their clinical management.

Unintended impacts of regulatory changes to British Columbia Methadone Maintenance Program on addiction and HIV-related outcomes: An interrupted time series analysis.

BACKGROUND: In February 2014, several regulatory reforms were introduced to the methadone maintenance treatment (MMT) program in British Columbia, Canada, including a switch to a ten-times more concentrated methadone formulation and restrictions in pharmacy delivery services. We evaluated possible unintended effects of these changes on illicit drug use patterns and HIV treatment outcomes among HIV-positive opioid users. METHODS: Data was drawn from ACCESS, a prospective community-recruited cohort of HIV-positive people who use illicit drugs in Vancouver, Canada. Interrupted Time Series Analyses were used to evaluate impacts of the policy change on monthly rates of MMT enrolment, illicit heroin injection, antiretroviral therapy (ART) adherence, and HIV viral suppression among HIV-positive opioid users between November 2012 and May 2015. RESULTS: A total of 331 HIV-positive opioid users were included. The MMT policy change led to a significant immediate 11.5% increase in heroin injection, and 15.9% drop in optimal ART adherence. A gradual increase in the prevalence of MMT enrolment after the policy change was also documented (0.9% per month). No changes in viral suppression rates were observed. CONCLUSION: We observed immediate increases in illicit heroin injection and decreases in ART adherence in the wake of regulatory changes to the local MMT program. These findings underscore the need to consider potential unintended effects of altering health programmes for vulnerable populations, the need to develop appropriate mitigation strategies, as well as to involve all relevant stakeholders in the planning and implementations of new policies.

Harder-to-reach people living with HIV experiencing high prevalence of all-type mental health disorder diagnosis.

People living with HIV/AIDS (PHA) often concurrently cope with mental health disorders that may greatly influence HIV and other health-related outcomes. The objective of this study was to examine the prevalence and correlates of self-reported mental health disorder diagnosis among a cohort of harder-to-reach HIV-positive individuals in British Columbia, Canada. Between 2007 and 2010, 1000 PHA who had initiated ART were enrolled in the Longitudinal Investigation into Supportive and Ancillary health services (LISA) study. Socio-demographic, behavioral, health-care utilization and psychosocial information was collected through interviewer-led questionnaires and linked to longitudinal clinical variables through the provincial Drug Treatment Program at the BC Centre for Excellence in HIV/AIDS. We identified the prevalence of all-type and specific mental health disorders among this population. Of the 916 participants included in this analysis, 494 (54%) reported ever having a mental health disorder diagnosis. Mood (85%) and anxiety (65%) disorders were the two most frequently reported mental health conditions. Self-reported all-type mental health disorder was independently associated with decreased overall functioning (adjusted odds ratio [AOR] = 0.90, 95% confidence interval [CI] = 0.83-0.98) and life satisfaction (AOR = 0.81, 95% CI = 0.74-0.89), and having higher stigma score (AOR = 1.11, 95%CI = 1.02-1.21). Participants reporting any mental health disorder were more likely to report a history of sexual assault (AOR = 2.45, 95% CI = 1.75-3.43) and to have used case management services (AOR = 1.63, 95%CI = 1.17-2.27). Our findings uncovered a high burden of mental health disorders among harder-to-reach PHA and suggest that PHA with at least one mental health disorder diagnosis are disproportionately impacted by sexual violence and stigma.

Cost-Effectiveness of the 'One4All' HIV Linkage Intervention in Guangxi Zhuang Autonomous Region, China.

BACKGROUND: In Guangxi Zhuang Autonomous Region, China, an estimated 80% of newly-identified antiretroviral therapy (ART)-eligible patients are not engaged in ART. Delayed ART uptake ultimately translates into high rates of HIV morbidity, mortality, and transmission. To enhance HIV testing receipt and subsequent treatment uptake in Guangxi, the Chinese Center for Disease Control and Prevention (CDC) executed a cluster-randomized trial to assess the effectiveness and cost-effectiveness of a streamlined HIV testing algorithm (the One4All intervention) in 12 county-level hospitals. OBJECTIVE: To determine the incremental cost-effectiveness of the One4All intervention delivered at county hospitals in Guangxi, China, compared to the current standard of care (SOC). PERSPECTIVE: Health System. TIME HORIZON: 1-, 5-and 25-years. METHODS: We adapted a dynamic, compartmental HIV transmission model to simulate HIV transmission and progression in Guangxi, China and identify the economic impact and health benefits of implementing the One4All intervention in all Guangxi hospitals. The One4All intervention algorithm entails rapid point-of-care HIV screening, CD4 and viral load testing of individuals presenting for HIV screening, with same-day results and linkage to counselling. We populated the model with data from the One4All trial (CTN-0056), China CDC HIV registry and published reports. Model outcomes were HIV incidence, mortality, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) of the One4All intervention compared to SOC. RESULTS: The One4All testing intervention was more costly than SOC (CNY 2,182 vs. CNY 846), but facilitated earlier ART access, resulting in delayed disease progression and mortality. Over a 25-year time horizon, we estimated that introducing One4All in Guangxi would result in 802 averted HIV cases and 1629 averted deaths at an ICER of CNY 11,678 per QALY gained. Sensitivity analysis revealed that One4All remained cost-effective at even minimal levels of effectiveness. Results were robust to changes to a range of parameters characterizing the HIV epidemic over time. CONCLUSIONS: The One4All HIV testing strategy was highly cost-effective by WHO standards, and should be prioritized for widespread implementation in Guangxi, China. Integrating the intervention within a broader combination prevention strategy would enhance the public health response to HIV/AIDS in Guangxi.

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.

Universal Coverage without Universal Access: Institutional Barriers to Health Care among Women Sex Workers in Vancouver, Canada.

BACKGROUND: Access to health care is a crucial determinant of health. Yet, even within settings that purport to provide universal health coverage (UHC), sex workers' experiences reveal systematic, institutionally ingrained barriers to appropriate quality health care. The aim of this study was to assess prevalence and correlates of institutional barriers to care among sex workers in a setting with UHC. METHODS: Data was drawn from an ongoing community-based, prospective cohort of women sex workers in Vancouver, Canada (An Evaluation of Sex Workers' Health Access). Multivariable logistic regression analyses, using generalized estimating equations (GEE), were employed to longitudinally investigate correlates of institutional barriers to care over a 44-month follow-up period (January 2010-August 2013). RESULTS: In total, 723 sex workers were included, contributing to 2506 observations. Over the study period, 509 (70.4%) women reported one or more institutional barriers to care. The most commonly reported institutional barriers to care were long wait times (54.6%), limited hours of operation (36.5%), and perceived disrespect by health care providers (26.1%). In multivariable GEE analyses, recent partner- (adjusted odds ratio [AOR] = 1.46, % 95% Confidence Interval [CI] 1.10-1.94), workplace- (AOR = 1.31, 95% CI 1.05-1.63), and community-level violence (AOR = 1.41, 95% CI 1.04-1.92), as well as other markers of vulnerability, such as self-identification as a gender/sexual minority (AOR = 1.32, 95% CI 1.03-1.69), a mental illness diagnosis (AOR = 1.66, 95% CI 1.34-2.06), and lack of provincial health insurance card (AOR = 3.47, 95% CI 1.59-7.57) emerged as independent correlates of institutional barriers to health services. DISCUSSION: Despite Canada's UHC, women sex workers in Vancouver face high prevalence of institutional barriers to care, with highest burden among most marginalized women. These findings underscore the need to explore new models of care, alongside broader policy changes to fulfill sex workers' health and human rights.

Near real-time monitoring of HIV transmission hotspots from routine HIV genotyping: an implementation case study.

BACKGROUND: HIV evolves rapidly and therefore infections with similar genetic sequences are likely linked by recent transmission events. Clusters of related infections can represent subpopulations with high rates of transmission. We describe the implementation of an automated near real-time system to monitor and characterise HIV transmission hotspots in British Columbia, Canada. METHODS: In this implementation case study, we applied a monitoring system to the British Columbia drug treatment database, which holds more than 32 000 anonymised HIV genotypes for nearly 9000 residents of British Columbia living with HIV. On average, five to six new HIV genotypes are deposited in the database every day, which triggers an automated reanalysis of the entire database. We extracted clusters of five or more individuals with short phylogenetic distances between their respective HIV sequences. The system generated monthly reports of the growth and characteristics of clusters that were distributed to public health officers. FINDINGS: In June, 2014, the monitoring system detected the expansion of a cluster by 11 new cases during 3 months, including eight cases with transmitted drug resistance. This cluster generally comprised young men who have sex with men. The subsequent report precipitated an enhanced public health follow-up to ensure linkage to care and treatment initiation in the affected subpopulation. Of the nine cases associated with this follow-up, all had already been linked to care and five cases had started treatment. Subsequent to the follow-up, three additional cases started treatment and most cases achieved suppressed viral loads. During the next 12 months, we detected 12 new cases in this cluster with reduction in the onward transmission of drug resistance. INTERPRETATION: Our findings show the first application of an automated phylogenetic system monitoring a clinical database to detect a recent HIV outbreak and support the ensuing public health response. By making secondary use of routinely collected HIV genotypes, this approach is cost-effective, attains near real-time monitoring of new cases, and can be implemented in all settings in which HIV genotyping is the standard of care. FUNDING: BC Centre for Excellence in HIV/AIDS, the Canadian Institutes for Health Research, the Genome Canada-CIHR Partnership in Genomics and Personalized Health, and the US National Institute on Drug Abuse.

Pre-exposure Prophylaxis Awareness Among Gay and Other Men who have Sex with Men in Vancouver, British Columbia, Canada.

Men who have sex with men (MSM) account for approximately half of Canada's new HIV infections. Pre-exposure prophylaxis (PrEP), a recently established and effective HIV prevention tool for MSM is currently not approved nor publicly funded. We recruited MSM via respondent-driven sampling to complete a self-administered computer-based interview. Stratified by HIV status, multivariable logistic regression identified factors associated with PrEP awareness. Of 673 participants, 102/500 (20.9 %) HIV-negative and 63/173 (26.5 %) HIV-positive men were aware of PrEP, but none had used it. One third of PrEP-aware MSM spoke about it with friends or sex partners. Self-declared knowledge was limited. Factors associated with PrEP awareness varied by HIV status, but included greater HAART optimism for HIV-negative MSM. Among HIV-negative MSM, being PrEP unaware was associated with younger age, not always having condoms, and preferring receptive versus insertive anal sex. Future longitudinal research should identify early adopters of PrEP and its associated impacts.

Pattern, Determinants, and Impact of HIV Spending on Care and Treatment in 38 High-Burden Low- and Middle-Income Countries.

UNLABELLED: : Achieving the 90-90-90 targets by 2020 requires increased focus, resources, and efficiency to provide earlier access to antiretroviral therapy (ART). METHODS: We used 2009 to 2013 National AIDS Spending Assessment data to assess HIV care and treatment spending in 38 high-burden, low- and middle-income countries (LMICs). RESULTS: In 2013, 23 of the 38 high-burden countries spent less than 50% of total HIV spending on care and treatment. HIV spending on ART per people living with HIV (PLHIV; adjusted) averaged US$299 (US$32-US$2463). During 2009 to 2013, a 10% increase in average spending on care and treatment per PLHIV was associated with an increase in ART coverage of 2.4% and a decrease in estimated AIDS-related death rate of 2.4 per 1000 PLHIV. DISCUSSION: HIV spending in high-burden LMICs does not consistently reflect the new science around the preventative and clinical benefits of earlier HIV diagnosis and ART initiation.

Cost-effectiveness of population-level expansion of highly active antiretroviral treatment for HIV in British Columbia, Canada: a modelling study.

BACKGROUND: Widespread HIV screening and access to highly active antiretroviral treatment (ART) were cost effective in mathematical models, but population-level implementation has led to questions about cost, value, and feasibility. In 1996, British Columbia, Canada, introduced universal coverage of drug and other health-care costs for people with HIV/AIDS and and began extensive scale-up in access to ART. We aimed to assess the cost-effectiveness of ART scale-up in British Columbia compared with hypothetical scenarios of constrained treatment access. METHODS: Using comprehensive linked population-level data, we populated a dynamic, compartmental transmission model to simulate the HIV/AIDS epidemic in British Columbia from 1997 to 2010. We estimated HIV incidence, prevalence, mortality, costs (in 2010 CAN$), and quality-adjusted life-years (QALYs) for the study period, which was 1997-2010. We calculated incremental cost-effectiveness ratios from societal and third-party-payer perspectives to compare actual practice (true numbers of individuals accessing ART) to scenarios of constrained expansion (75% and 50% probability of accessing ART). We also investigated structural and parameter uncertainty. FINDINGS: Actual practice resulted in 263 averted incident cases compared with 75% of observed access and 676 averted cases compared with 50% of observed access to ART. From a third-party-payer perspective, actual practice resulted in incremental cost-effectiveness ratios of $23 679 per QALY versus 75% access and $24 250 per QALY versus 50% access. From a societal perspective, actual practice was cost saving within the study period. When the model was extended to 2035, current observed access resulted in cumulative savings of $25·1 million compared with the 75% access scenario and $65·5 million compared with the 50% access scenario. INTERPRETATION: ART scale-up in British Columbia has decreased HIV-related morbidity, mortality, and transmission. Resulting incremental cost-effectiveness ratios for actual practice, derived within a limited timeframe, were within established cost-effectiveness thresholds and were cost saving from a societal perspective. FUNDING: BC Ministry of Health, National Institute of Drug Abuse at the US National Institutes of Health.

Compulsory drug detention exposure is associated with not receiving antiretroviral treatment among people who inject drugs in Bangkok, Thailand: a cross-sectional study.

BACKGROUND: Thailand has experienced a longstanding epidemic of HIV among people who inject drugs (PWID). However, antiretroviral treatment (ART) coverage among HIV-positive PWID has historically remained low. While ongoing drug law enforcement involving periodic police crackdowns is known to increase the risk of HIV transmission among Thai PWID, the impact of such drug policy approaches on the ART uptake has been understudied. Therefore, we sought to identify factors associated with not receiving ART among HIV-positive PWID in Bangkok, Thailand, with a focus on factors pertaining to drug law enforcement. METHODS: Data were collected from a community-recruited sample of HIV-positive PWID in Bangkok who participated in the Mitsampan Community Research Project between June 2009 and October 2011. We identified factors associated with not receiving ART at the time of interview using multivariate logistic regression. RESULTS: In total, 128 HIV-positive PWID participated in this study, with 58 (45.3%) reporting not receiving ART at the time of interview. In multivariate analyses, completing less than secondary education (adjusted odds ratio [AOR]: 3.32 ; 95% confidence interval [CI]: 1.48 - 7.45), daily midazolam injection (AOR: 3.22, 95% CI: 1.45 - 7.15) and exposure to compulsory drug detention (AOR: 3.36, 95% CI: 1.01 - 11.21) were independently and positively associated with not receiving ART. Accessing peer-based healthcare information or support services was independently and positively associated with receiving ART (AOR: 0.21, 95% CI: 0.05 - 0.84). CONCLUSIONS: Approximately half of our study group of HIV-positive PWID reported not receiving ART at the time of interview. Daily midazolam injectors, those with lower education attainment, and individuals who had been in compulsory drug detention were more likely to be non-recipients of ART whereas those who accessed peer-based healthcare-related services were more likely to receive ART. These findings suggest a potentially adverse impact of compulsory drug detention and highlight the need to expand interventions to facilitate access to ART among HIV-positive PWID in this setting.