Building the Case for Localized Approaches to HIV: Structural Conditions and Health System Capacity to Address the HIV/AIDS Epidemic in Six US Cities.

Since the discovery of the secondary preventive benefits of antiretroviral therapy, national and international governing bodies have called for countries to reach 90% diagnosis, ART engagement and viral suppression among people living with HIV/AIDS. The US HIV epidemic is dispersed primarily across large urban centers, each with different underlying epidemiological and structural features. We selected six US cities, including Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle, with the objective of demonstrating the breadth of epidemiological and structural differences affecting the HIV/AIDS response across the US. We synthesized current and publicly-available surveillance, legal statutes, entitlement and discretionary funding, and service location data for each city. The vast differences we observed in each domain reinforce disparities in access to HIV treatment and prevention, and necessitate targeted, localized strategies to optimize the limited resources available for each city's HIV/AIDS response.

Non-HIV-related health care utilization, demographic, clinical and laboratory factors associated with time to initial retention in HIV care among HIV-positive individuals linked to HIV care.

OBJECTIVES: The aim of the study was to explore non-HIV-related health care service (NHRHS) utilization, demographic, clinical and laboratory factors associated with timely initial "retention" in HIV care among individuals "linked" to HIV care in British Columbia (BC), Canada. METHODS: We conducted a Weibull time-to-initial-retention analysis among BC Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort participants linked in 2000-2010, who had ≥ 1 year of follow-up. We defined "linked" as the first HIV-related service accessed following HIV diagnosis and "retained" as having, within a calendar year, either: (i) at least two HIV-related physician visits/diagnostic tests or (ii) at least two antiretroviral therapy (ART) dispensations, ≥ 3 months apart. Individuals were followed until they were retained, died, their last contact date, or until 31 December 2011, whichever occurred first. RESULTS: Of 5231 linked individuals (78% male; median age 39: (Q1-Q3: 32-46) years], 4691 (90%) were retained [median time to initial retention of 9 (Q1-Q3: 5-13) months] by the end of follow-up and 540 (10%) were not. Eighty-four per cent of not retained and 96% of retained individuals used at least one type of NHRHS during follow-up. Individuals who saw a specialist for NHRHS during follow-up had a shorter time to initial retention than those who did not [adjusted hazard ratio (aHR) 2.79; 95% confidence interval (CI): 2.47-3.16]. However, those who saw a general practitioner (GP) for NHRHS (aHR 0.79; 95% CI: 0.74-0.84) and those admitted to the hospital for NHRHS (aHR 0.60; 95% CI: 0.54-0.67), versus those who did/were not, respectively, had longer times to initial retention, as did female patients, people who inject drugs (PWID) and individuals < 40 years old. CONCLUSIONS: Overall, 84% of not retained individuals used some type of NHRHS during follow-up. Given that 71% of not retained individuals used GP NHRHS, our results suggest that GP-targeted interventions may be effective in improving time to initial retention.

Cost-effectiveness analysis along the continuum of HIV care: how can we optimize the effect of HIV treatment as prevention programs?

The cascade of HIV care has been proposed as a useful tool to monitor health system performance across the key stages of HIV care delivery to reduce morbidity, mortality, and HIV transmission, the focal points of HIV Treatment as Prevention campaigns. Interventions to improve the cascade at its various stages may vary substantially in their ability to deliver health value per amount expended. In order to meet global antiretroviral treatment access targets, there is an urgent need to maximize the value of health spending by prioritizing cost-effective interventions. We executed a literature review on economic evaluations of interventions to improve specific stages of the cascade of HIV care. In total, 33 articles met the criteria for inclusion in the review, 22 (67 %) of which were published within the last 5 years. Nonetheless, substantial gaps in our knowledge remain, particularly for interventions to improve linkage and retention in HIV care in developed and developing-world settings and generalized and concentrated epidemics. We make the case here that the attention of scientists and policymakers needs to turn to the development, implementation, and rigorous evaluation of interventions to improve the various stages of the cascade of HIV care.

Development and validation of health system performance measures for opioid use disorder in British Columbia, Canada.

BACKGROUND: Performance measurement provides an evidence-based means to inform development of interventions to improve the quality of care for people who use opioids. We aimed to develop and assess the predictive validity of health system performance measures for opioid use disorder (OUD) in British Columbia (BC), Canada. METHODS: Performance measures were generated using retrospective population-level administrative datasets (both provincial and regional) and publicly-reported retrospective data according to four domains (care engagement, clinical guideline compliance, integration, and healthcare utilization). The adjusted odds ratio was estimated via generalized linear mixed models to determine predictive validity for all-cause hospitalization or mortality within 6 months of measurement. FINDINGS: A total of 102 performance measures were constructed. We identified 55,470 diagnosed PWOUD, and 39,456 ever engaged in opioid agonist treatment (OAT). We found divergent rates of treatment for concurrent conditions (7.4% for alcohol use disorder to 80.1% for HIV/AIDS), low levels of linkage to OAT and other outpatient care following acute care, and increasing levels of service provision, including increases in OAT prescribers and pharmacies, naloxone kit distribution and overdose prevention site visitation. Our analyses on the predictive validity measures largely supported a priori hypotheses on the direction of effect on the outcome. CONCLUSIONS: We identified a range of priorities to improve the quality of care for PWOUD, with critical gaps in linkage to care through acute care settings and long-term engagement in OAT. The proposed measures can be derived for geographic and clinical subgroups and updated over time, providing a basis to monitor and evaluate efforts to address the public health burden of OUD.

Determinants of selection into buprenorphine/naloxone among people initiating opioid agonist treatment in British Columbia.

BACKGROUND: Studies assessing the comparative effectiveness of methadone versus buprenorphine/naloxone for opioid use disorder in real-world settings are rare - challenged by structural differences in delivery across settings and factors influencing treatment selection. We identified determinants of selection into buprenorphine/naloxone and quantified contributions of individual and provider-level covariates in a setting delivering both medications within the same healthcare settings. METHODS: Utilizing linked health administrative datasets, we conducted a retrospective cohort study of people with opioid use disorder (PWOUD) receiving opioid agonist treatment (OAT) in British Columbia, Canada, from 2008-2017. Determinants of buprenorphine/naloxone selection were identified using a generalized linear mixed model with random intercept terms for providers and individuals. We determined the influence of individual demographics, clinical history, measures of provider experience and preference, and dates of key policy changes. RESULTS: A total of 39,605 individuals experienced 178,976 OAT episodes (methadone:139,439(77.9 %);buprenorphine/naloxone:39,537(22.1 %)). Male sex, less OAT experience, younger age, mental health conditions and chronic pain were associated with higher odds of buprenorphine/naloxone prescription. For providers, higher client-attachment, more complex OAT case-mixes, and higher buprenorphine/naloxone prescribing-preference were also associated with higher odds of buprenorphine/naloxone prescription. Observed individual-level covariates explained 9.7 % of variance in odds of buprenorphine/naloxone selection, while observed provider-level covariates explained 20.0 %. Controlling for covariates, residual unmeasured between-individual variance accounted for 18.5 % of the explained variation in the odds of buprenorphine/naloxone selection, while unmeasured between-provider variance accounted for 28.4 %. CONCLUSION: Provider characteristics were more influential in selection of buprenorphine/naloxone over methadone informing subsequent analyses of comparative effectiveness of these regimens.

Gender differences in mortality among treated opioid dependent patients.

AIMS: To assess gender differences in characteristics, mortality rates, and the causes and predictors of death among treated opioid-dependent individuals. METHODS: Linked vital statistics data were obtained for all individuals first enrolled in publicly funded pharmacological treatment for opioid dependence in California from 2006 to 2010. Standardized mortality ratios (SMR) were calculated by gender. Cox proportional hazards models with time-varying covariates were fitted to determine the effect of gender on the hazard of all-cause mortality, controlling for covariates. RESULTS: Over a median 2.6 years (interquartile range: 1.4-3.7), 1.031 deaths were observed, including 2.2% (259/11,564) of women and 3.7% (772/20,758) of men. Women had a greater increased risk of mortality compared to the general population (SMR 5.1 95% CI: 4.5, 5.7) than men (SMR 4.3 95% CI: 4.0, 4.6). The relative risk of death for women compared with men was 1.18 (95% CI: 1.02, 1.36). Women had a lower instantaneous hazard of all-cause mortality than men (HR 0.58, 95% CI 0.50, 0.68), controlling for other factors. Significant interaction effects indicated that among men, mortality risk was decreased by full-time employment and increased by non-daily heroin use (relative to daily use) and medical problems. Concurrent opioid and methamphetamine/cocaine use increased mortality risk among women and decreased it among men. CONCLUSIONS: Treatment for opioid dependence is likely to reduce mortality risk among men by addressing employment and medical problems, and via interventions to reduce overdose risk after heroin abstinence, and among women by attending to the concurrent use of methamphetamine/cocaine and opioids.

Short term health-related quality of life improvement during opioid agonist treatment.

BACKGROUND: Opioid dependence is associated with high levels of morbidity, yet sparse data exists regarding the health-related quality of life (HRQoL) of individuals with opioid dependence, particularly following treatment initiation. To inform cost-effectiveness analyses of treatment modalities, this study investigates short-term changes in HRQoL following enrollment into opioid agonist treatment (OAT), across treatment modalities and patient subgroups. METHODS: Data was analyzed from the Starting Treatment with Agonist Replacement Therapies (START) and Prescription Opioid Addiction Treatment Studies (POATS) randomized controlled trials. Participants included individuals dependent on prescription opioids (POs) or heroin, receiving limited-term or time-unlimited treatment. PO- or heroin-users in START received buprenorphine/naloxone (BUP/NX) or methadone (MET) over 24 weeks. PO-users in POATS received psychosocial care and short-term (4-week) taper with BUP/NX, with non-responders offered subsequent extended (12-week) stabilization and taper. HRQoL was assessed using the short-form SF-6D while in and out of OAT, with distinction between MMT and BUP/NX in START. Linear mixed effects regression models were fitted to determine the independent effects of OAT on HRQoL and characterize HRQoL trajectories. RESULTS: Treatment had a similar immediate and modest positive association with HRQoL in each patient subgroup. The association of OAT on HRQoL was statistically significant in each model, with effect sizes between 0.039 (heroin-users receiving BUP/NX) and 0.071 (PO-users receiving MET). After initial improvement, HRQoL decreased slightly, or increased at a diminished rate. CONCLUSIONS: OAT, whether delivered in time-limited or unlimited form, using BUP/NX or MET, is associated with modest immediate HRQoL improvements, with diminishing benefits thereafter.

The 'Expanded HIV care in opioid substitution treatment' (EHOST) cluster-randomized, stepped-wedge trial: A study protocol.

The public health response to HIV/AIDS has turned its focus onto optimizing health care system delivery to maximize case identification, access and sustained engagement in antiretroviral treatment (ART). Opioid Agonist Treatment (OAT) provides a critical opportunity for HIV testing and linkage to ART. The EHOST study is a cluster-randomized, stepped-wedge trial to evaluate a prescriber-focused intervention to increase HIV testing rates, and optimize ART engagement and retention outcomes among individuals engaged in OAT. The study will encompass all drug treatment clinics currently admitting patients for the treatment of opioid use disorder across the province of British Columbia, encompassing an estimated 90% of the OAT caseload. The trial will be executed over a 24-month period, with groups of clinics receiving the intervention in 6-month intervals. Evaluation of the proposed intervention's effectiveness will focus on three primary outcomes: (i) the HIV testing rate among those not known to be HIV positive; (ii) the rate of ART initiation among those not on ART; and (iii) the rate of ART continuation among those on ART. A difference-in-differences analytical framework will be applied to estimate the intervention's effect. This approach will assess site-specific changes in primary outcomes across clusters while adjusting for potential residual heterogeneity in patient case mix, volume, and quality of care across clinics. Statistical analysis of outcomes will be conducted entirely with linked population-level administrative health datasets. Facilitated by established collaborations between key stakeholders across the province, the EHOST intervention promises to optimize HIV testing and care within a marginalized and hard-to-reach population.

Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users.

AIMS: Characterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. DESIGN: Pooled analysis of prospective cohort studies. SETTINGS: Illicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. PARTICIPANTS: We used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. MEASUREMENTS: Monthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. FINDINGS: Across primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions toward cessation. CONCLUSIONS: PH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions.

Increases in the availability of prescribed opioids in a Canadian setting.

BACKGROUND: The nonmedical use of prescribed opioids (POs) has increased across North America over the past decade. Our objective was to identify changes in the availability of POs and other illicit drugs among drug users in a Canadian setting. METHODS: Information on the availability of illicit drugs was collected in standardized interviews from a large observational research program involving illicit drug users in Vancouver, British Columbia from 2006 to 2010. The primary outcome was the perceived availability of a set of six POs (aspirin/oxycodone, hydromorphone, oxycodone, morphine, acetaminophen/codeine and methadone) among individuals reporting ever using POs. Availability was measured in three levels: not available, delayed availability (available ≥10 min), and immediate availability (available <10 min). Multivariate ordinal logistic regression models were executed to estimate the trend in PO availability, controlling for individual characteristics hypothesized to influence availability. RESULTS: 1871 individuals were followed during the study period (2006-2010), including 583 (31.2%) women. The availability of POs increased over time, regardless of changes in the characteristics of cohort entrants. These increases were observed while the availability of traditional drugs of abuse (e.g., heroin and cocaine) remained constant. The adjusted odds of delayed availability vs. unavailability were between 34% (hydromorphone) and 71% (acetaminophen/codeine) greater in each calendar year. DISCUSSION: The availability of POs among drug users in a Canadian setting increased markedly over a relatively short timeframe, despite persistent and high availability of heroin and cocaine. Further study is required to determine the context of use of POs, associated harms, as well as policy responses to increasing availability.

The effect of homelessness on hospitalisation among patients with HIV/AIDS.

The purpose of this study was to determine the effect of homelessness on the costs and patterns of hospitalisation in patients with HIV/AIDS. A retrospective longitudinal study design, based on medical records data covering 2,768 person-years of observation between 1997 and 2003 on patients with HIV/AIDS, was employed. A contextual measure of neighbourhood socioeconomic status (SES) was also used to uncover differences among low- and high-SES neighbourhood dwellers. The association of homelessness and neighbourhood SES with total annual hospitalisation costs, length of stay, numbers of hospital and emergency department admissions and the probability of an operating room procedure, controlling for other covariates, was assessed using multivariate regression analysis. Our results suggest that the homeless and low-SES neighbourhood residents had a large proportion of total costs attributable to admissions for acute events related to the progression of disease. Hospitalisations for planned operating room procedures comprised a relatively larger proportion of hospitalisation costs for high-SES neighbourhood residents. One implication of our findings is that improvements in the continuity of care and cost savings on inpatient care may be realised through further development of social assistance programs aimed at reaching the homeless and residents of low-SES neighbourhoods.