Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach.

This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody-positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012), with a Core-E2 sequence were included. Time-stamped phylogenetic trees were inferred, and phylogenetic clustering was determined by time to most common recent ancestor. Latent classes were estimated, and the association with the phylogenetic clustering outcome was assessed using an inclusive classify/analyse approach. Among 699 HCV RNA-positive participants (26% female, 24% HIV+), recent drug use included injecting cocaine (80%), injecting heroin (70%), injecting cocaine/heroin (ie, speedball, 38%) and crack cocaine smoking (28%). Latent class analysis identified four distinct subgroups of drug use typologies: (i) cocaine injecting, (ii) opioid and cocaine injecting, (iii) crack cocaine smoking and (iv) heroin injecting and currently receiving opioid substitution therapy. After adjusting for age and HIV infection, compared to the group defined by heroin injecting and currently receiving opioid substitution therapy, the odds of phylogenetic cluster membership was greater in the cocaine injecting group (adjusted OR [aOR]: 3.06; 95% CI: 1.73, 5.42) and lower in the crack cocaine smoking group (aOR: 0.06; 95% CI: 0.01, 0.48). Combining latent class and phylogenetic clustering analyses provides novel insights into the complex dynamics of HCV transmission. Incorporating differing risk profiles associated with drug use may provide opportunities to further optimize and target HCV treatment and prevention strategies.

An assessment of the relationship between the World Health Organization HIV drug resistance early warning indicators and HIV drug resistance acquisition.

OBJECTIVES: The World Health Organization (WHO)'s HIV drug resistance (HIVDR) early warning indicators (EWIs) measure antiretroviral therapy (ART)-site factors associated with HIVDR prevention, without HIVDR laboratory testing. We assessed the relationship between EWIs and HIVDR acquisition using data from British Columbia, Canada. METHODS: Eligible patients were ART-naïve, were ≥ 19 years old, had initiated ART between 1 January 2000 and 31 December 2012, had ≥ 15 months of follow-up, and were without transmitted HIVDR. Patients were followed for acquired HIVDR until 31 March 2014, the last contact date, or death. We built logistic regression models to assess the associations and predictive ability of individual indicators and of the EWI Score (the number of indicators for which a patient did not meet the criteria) on HIVDR acquisition (to any class of HIVDR, lamivudine (3TC)/emtricitabine (FTC), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs)]). RESULTS: All explored EWIs were associated with at least one class of HIVDR, with the exception of 'ART prescribing practices'. We observed a dose-response relationship between acquiring HIVDR to any antiretroviral class and an increasing EWI score in our predictive logistic regression model. The area under the curve was 0.848 (excellent discrimination). The adjusted odds ratios for acquiring any class of HIVDR for an EWI score of 1, 2 and ≥ 3 versus 0 were 2.30 [95% confidence Interval (CI) 1.21-4.38], 3.35 (95% CI: 1.86-6.03) and 7.26 (95% CI: 4.18-12.61), respectively. CONCLUSIONS: Several EWIs were associated with and predictive of HIVDR, supporting the WHO EWIs as a component of the HIVDR prevention method in settings where HIVDR testing is not routinely or widely available.

Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy.

OBJECTIVES: To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. METHODS: We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. RESULTS: Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. CONCLUSIONS: Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible.

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.

Phylogenetic clustering of hepatitis C virus among people who inject drugs in Vancouver, Canada.

UNLABELLED: Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody-positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1), and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age≥40, adjusted odds ratio [AOR]=1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR=1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR=3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36). CONCLUSION: In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations.

Performance of HIV-1 drug resistance testing at low-level viremia and its ability to predict future virologic outcomes and viral evolution in treatment-naive individuals.

BACKGROUND: Low-level viremia (LLV; human immunodeficiency virus [HIV-1] RNA 50-999 copies/mL) occurs frequently in patients receiving antiretroviral therapy (ART), but there are few or no data available demonstrating that HIV-1 drug resistance testing at a plasma viral load (pVL) <1000 copies/mL provides potentially clinically useful information. Here, we assess the ability to perform resistance testing by genotyping at LLV and whether it is predictive of future virologic outcomes in patients beginning ART. METHODS: Resistance testing by genotyping at LLV was attempted on 4915 plasma samples from 2492 patients. A subset of previously ART-naive patients was analyzed who achieved undetectable pVL and subsequently rebounded with LLV (n = 212). A genotypic sensitivity score (GSS) was calculated based on therapy and resistance testing results by genotyping, and stratified according to number of active drugs. RESULTS: Eighty-eight percent of LLV resistance assays produced useable sequences, with higher success at higher pVL. Overall, 16 of 212 (8%) patients had pretherapy resistance. Thirty-eight of 196 (19%) patients without pretherapy resistance evolved resistance to 1 or more drug classes, primarily the nucleoside reverse transcriptase (14%) and/or nonnucleoside reverse transcriptase (9%) inhibitors. Patients with resistance at LLV (GSS <3) had a 2.1-fold higher risk of virologic failure (95% confidence interval, 1.2- to 3.7-fold) than those without resistance (P = .007). Progressively lower GSS scores at LLV were associated with a higher increase in pVL over time (P < .001). Acquisition of additional resistance mutations to a new class of antiretroviral drugs during LLV was not found in a subset of patients. CONCLUSIONS: Routine HIV-1 genotyping of LLV samples can be performed with a reasonably high success rate, and the results appear predictive of future virologic outcomes.

Modelling clinical progression and health care utilization of HIV-positive patients in British Columbia prior to death.

OBJECTIVES: The extent to which clinical progression of HIV-positive patients leads to an increase in health care utilization, especially prior to their death, is unknown. Thus, we modelled trends in CD4 cell count and emergency department utilization and the likelihood of an emergency department visit leading to a transfer to an acute care-level facility prior to a patient's death from nonaccidental causes. METHODS: Eligible patients initiated highly active antiretroviral therapy (HAART) in British Columbia between August 1996 and June 2006 (n = 457). Patients were followed until their death, which occurred on or before 30 June 2007 (period in which the emergency department visit data were available). Trends were modelled using generalized mixed effects. RESULTS: Patients experienced a significantly steep decline in CD4 cell count and a corresponding increase in the number of emergency department visits and transfers to acute-level facilities in the 5 years prior to death. For every 6-month interval prior to death, the CD4 cell count decreased by 13.22 cells/µL, the risk of experiencing an emergency department visit increased by 9%, and among those ever admitted, the odds ratio of being transferred to an acute care-level facility increased by 3%. CONCLUSIONS: We showed that patients experienced a steep decline in CD4 cell count, which was associated with an increase in health care utilization prior to their death. These findings highlight the substantial residual avoidable burden that unsuccessfully managed HIV disease poses, even in the HAART era. Further strategies to enhance sustained and successful engagement in care are urgently needed to mitigate high health care utilization.

The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

BACKGROUND: We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). METHODS: The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. RESULTS: Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/µL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. CONCLUSION: While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort.

OBJECTIVE: The aim of the study was to evaluate time to virological suppression in a cohort of individuals who started highly active antiretroviral therapy (HAART), and to explore the factors associated with suppression. METHODS: Eligible participants were HIV-positive individuals from a multi-site Canadian cohort of antiretroviral-naïve patients initiating HAART on or after 1 January 2000. Viral load and CD4 measurements within 6 months prior to HAART initiation were assessed. Univariate and multivariate analyses were conducted using piecewise survival exponential models where time scale was divided into intervals (<10 months; ≥10 months). Virological suppression was defined as the time to the first of at least two consecutive viral load measurements <50 HIV-1 RNA copies/mL. RESULTS: A total of 3555 individuals were included in the study, of median age 40 years [interquartile range (IQR) 34-47 years]. Eighty per cent were male, 18% had a history of injecting drug use (IDU), and 13% presented with an AIDS-defining illness at baseline. The median time to suppression was 4.55 months (IQR 2.99-7.89 months). In multivariate analyses, older age, male sex, treatment in Ontario rather than British Columbia, non-IDU history, and having an AIDS diagnosis at baseline predicted increased likelihood of suppression. Patients with low baseline viral load were more likely to have suppression [4-5 log(10) copies/mL, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.18-1.38; <4 log(10) copies/mL, HR 1.49, 95% CI 1.32-1.68] than patients with baseline viral load ≥5 log(10) copies/mL; however, this effect ceased after 18 months of follow-up. Suppression was more likely with nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted HAART. CONCLUSION: Identification of patients at risk for diminished likelihood of virological suppression will allow focusing of efforts and the utilization of resources to maximize the benefits of HAART.

Suboptimal use of HIV drug resistance testing in a universal health-care setting.

HIV drug resistance testing is recommended as routine part of clinical practice in HIV/AIDS treatment and care. Our objective is to assess the determinants of accessing HIV drug resistance testing and examine the factors associated with resistance testing prior to or after starting highly active antiretroviral therapy (HAART) in a setting where access to HIV care is free and universal. The Longitudinal Investigation into Supportive and Ancillary health services (LISA) study is an open prospective cohort of HIV-positive persons on HAART in British Columbia (BC), Canada. Non-clinical data were collected through an interviewer-administered survey and clinical data were obtained through the BC Centre for Excellence in HIV/AIDS Drug Treatment Program. Independent associations between key explanatory variables and resistance testing were analyzed using logistic regression. We restricted our post-HAART analyses to those patients who met the criteria for resistance testing after HAART initiation. Of 359 LISA participants who started HAART after 2000 and at a time when resistance testing was available free of charge, almost half did not receive a baseline resistance test. Post-HAART initiation, 165 of 359 study subjects met the criteria for resistance testing based on current therapeutic guidelines due to virological failure. About 37.6% of them remain untested for resistance. Multivariable analyses show that baseline testing was less likely performed for persons of Aboriginal ethnicity and more likely performed for patients initiating HAART in 2004 or after. Additionally, persons initiating HAART in 2004 or after were less likely to have received a resistance test after virologic failure. Our results show that despite existing clinical guidelines, resistance testing is underused, even in an environment where the service is available free of charge. Further, resistance testing is particularly underutilized among vulnerable populations. Urgent efforts are needed to ensure the optimal use of resistance testing at baseline and at the time of virologic failure as recommended by current guidelines.

Non-medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme.

BACKGROUND: We examined clinical outcomes, patient characteristics and trends over time of non-medically supervised treatment interruptions (TIs) from a free-of-charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada. METHODS: Data from ART-naïve individuals > or =18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having > or =3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment. RESULTS: A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co-infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty-eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS-defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART. CONCLUSION: Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years.

Mortality is influenced by locality in a major HIV/AIDS epidemic.

OBJECTIVES: The aim of the study was to compare the risks of death among HIV-infected patients on highly active antiretroviral therapy (HAART) in two proximate, yet distinct neighbourhoods: a neighbourhood with a high concentration of gay men, and a neighbourhood with a high concentration of injecting drug users. METHODS: We compared the clinical and socioeconomic characteristics of HIV-infected patients from the two neighbourhoods entering the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program from 1 September 1997 to 30 November 2005, using contingency table statistics. Cox survival models and Kaplan-Meier methods were used to estimate the cumulative mortality rates. RESULTS: We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV-experienced physician and be less adherent. Patients in the neighbourhood with a high concentration of gay men were more likely to have AIDS. Mortality was significantly higher for patients in the neighbourhood with a high concentration of injecting drug users [hazard ratio (HR) 3.01; 95% confidence interval (CI) 1.73, 5.24]. CONCLUSIONS: A threefold increase was observed in the risk of death among HIV-infected individuals on HAART in the neighbourhood with a high concentration of injecting drug users relative to the neighbourhood with a high concentration of gay men. The implications of this study should be assessed in similar HIV/AIDS epicentres.

Health care services utilization stratified by virological and immunological markers of HIV: evidence from a universal health care setting.

OBJECTIVE: The aim of the study was to determine rates of utilization of in-patient, out-patient and laboratory services stratified by virological and immunological markers of HIV disease among patients on antiretroviral treatment in British Columbia, Canada. METHODS: We estimated resource utilization for in-patient visits, out-patient visits, and laboratory tests among patients initiating antiretroviral treatment between 1 April 1994 and 31 December 2000, with follow-up to 31 March 2001. Resource use was stratified by CD4 cell count and plasma HIV viral load (pVL) at the time of utilization and rates per 100 patient-years were calculated for each health care resource. RESULTS: A total of 2718 patients were included in our analyses. The overall rates of in-patient visits, out-patient visits, and laboratory tests were 902, 3001 and 840 per 100 patient-years, respectively. Utilization was higher for patients with low CD4 cell counts and high pVLs when compared with patients with high CD4 cell counts and low pVLs. CONCLUSIONS: Patients with low CD4 cell counts and high pVLs had the highest use of health care services. Regular follow-up with health care providers in an out-patient setting, allowing for proper monitoring and maintenance of HIV care, is important in minimizing unnecessary and potentially costly in-patient care.

Chylous ascites: a late complication of intra-abdominal Mycobacterium avium complex immune reconstitution syndrome in HIV-infected patients.

Chylous ascites related to Mycobacterium avium complex (MAC) in HIV-infected patients is rare, with only six cases reported in the English literature. We report a series of six cases from a single institution. During the past six years, chylous ascites was diagnosed in six (35%) of 17 AIDS patients, all of whom had previously been diagnosed with intra-abdominal MAC immune reconstitution syndrome (MAC-IRS). A review of medical records identified no other cases of chylous ascites among HIV-positive patients over the past 13 years (1994-2007), and the incidence was estimated at one in 2248 HIV-positive admissions. The ascitic fluid had a milky appearance and a median triglyceride level of 4.07 mmol/L (range 3.19-29.6 mmol/L) (360 mg/dL, range 282-2620 mg/dL). After a median follow-up of 20 months, five (83%) of six patients survived. Chylous ascites is a late complication of intra-abdominal MAC-IRS, and is usually associated with a favourable prognosis.

Longitudinal trends of HIV drug resistance in a large Canadian cohort, 1996-2016.

OBJECTIVES: We aim to identify long-term trends in HIV drug resistance before and after combined antiretroviral therapy (cART) initiation. METHODS: IAS-USA (2015) mutations were identified in 23 271 HIV protease-reverse transcriptase sequences from 6543 treatment naïve adults in British Columbia. Participants who started cART between 1996 and 2014 were followed until April 2016. Equality of proportions test was used to compare the percentage of participants with acquired drug resistance (ADR) or transmitted drug resistance (TDR) in 1996, to those in 2014. Kaplan-Meier was used to estimate time to ADR in four drug resistance categories. Multivariable regression odds ratios (OR) of ADR for select clinical variables were determined by 5-year eras of cART initiation. RESULTS: The proportion of individuals with ADR declined from 39% (51/132) to 3% (8/322) in 1996-2014 (p <0.0001), while the proportion with TDR increased from 12% (16/132) to 18% (59/322) (p 0.14). The estimated proportions of individuals with ADR rose to 29% (NNRTI), 28% (3TC/FTC), 14% (other nRTI), and 7% (PI) after >16 years of therapy. After 5 years on therapy, participants initiating cART in 1996-2000 had 5.5-times more 3TC/FTC ADR, 5.3-times more other nRTI ADR, 4.7-times more NNRTI ADR, and 24-times more PI ADR than those starting in 2011-2014. The individuals with highest odds of developing ADR in 1996-2010 were adherent to regimens at levels between 60% and 80%, which shifted to <40% adherent in 2011-2014. CONCLUSIONS: HIV drug resistance transitioned from being primarily selected de-novo to being driven by TDR. Among those who started treatment in the past 5 years, ADR is rare and observed mostly in the lowest adherence strata.

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.