Drug use patterns associated with risk of non-adherence to antiretroviral therapy among HIV-positive illicit drug users in a Canadian setting: a longitudinal analysis

Data for these analyses were derived from the Vancouver Injection Drug Users Study (VIDUS) and AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), two ongoing prospective observational cohorts of illicit drug users in Vancouver, Canada. Beginning in 1996, persons who had injected illicit drugs other than cannabinoids in the previous month were recruited into VIDUS. Since 2005, persons who used illicit drugs and were HIV-seropositive at baseline or during the study are subsequently followed in ACCESS. Both cohorts use identical recruitment and follow-up procedures to allow for combined analyses.

Described in detail previously [8-10], the cohorts were populated through snowball sampling and extensive street outreach in the city’s Downtown Eastside neighbourhood, an area with an open drug market and high levels of injection drug use, poverty and HIV infection [11,12]. Participants of these studies were 18 years of age or older and provided written informed consent. At baseline and every six-month follow-up interview, participants answered a standardized interviewer-administered questionnaire, were examined by a study nurse and provided blood samples for serologic analysis. Participants are actively referred to primary care services and drug treatment programs where available and were provided with a $30 stipend per study visit. A unique feature of these studies is that the Canadian province of British Columbia delivers all HIV care including medications at no charge and employs a system in which every instance of antiretroviral dispensation and all HIV clinical monitoring is captured through a centralized registry [8,13,14]. This allows a comprehensive retrospective and prospective clinical HIV profile for all participants. Ethics approval has been provided annually by University of British Columbia/Providence Health Care Research Ethics Board.

The present analyses considered all HIV-seropositive participants who had been dispensed at least one day of antiretroviral therapy (ART) between May 1996 and May 2013. The primary outcome of interest in this study was adherence to ART in the six month period prior to each study interview. As in previous studies [9,15], we estimated antiretroviral adherence using a validated measure based on pharmacy refill records provided by the confidential record linkage with the database of the Drug Treatment Program. Specifically, adherence was estimated by calculating the number of days for which an individual was dispensed ART in the previous six months over the number of days since they had initiated ART, capped at 180 days. We dichotomized this measure as ≥95% vs. <95%. The cut-off threshold of 95% was chosen as this level has previously been shown to be closely associated with virological suppression and survival [15,16].

Explanatory variables of interest included socio-demographic data: age (per 10 years older), gender (female vs. male), and Caucasian ancestry (yes vs. no). Variables related to drug use characteristics included: heroin injection (yes vs. no), cocaine injection (yes vs. no), amphetamine injection (e.g., “speed”, “uppers”, crystal methamphetamine; yes vs. no), crack cocaine smoking (yes vs. no), and enrollment in methadone maintenance therapy (yes vs. no). All drug use characteristics defined above were treated as time-updated based on questionnaire data pertaining to the six month period prior to each study interview [8,13]. We also included CD4 cell count (per 100 cells/μL increase) at ART initiation using the last CD4 cell count observation conducted prior to the first dispensation of ART. We also included a time-updated variable measuring the time since the participant initiated antiretroviral therapy (per year increase), using records from this setting’s comprehensive antiretroviral dispensary.

As a first step, we visually inspected trends in the proportion of all participants reporting heroin injecting, cocaine injecting, crack smoking and amphetamine injecting at each interview period. Next, we visually inspected changes in median adherence rate at each interview period over time.

Since serial measures for each subject (i.e., multiple 6-month observation periods) were available for many participants, we estimated the relationships between different socio-demographic, drug use and clinical factors and adherence using generalized estimating equations (GEE) with a logit-link function. As a first step, we conducted bivariable GEE analyses to determine which variables were statistically associated with adherence in unadjusted analyses. To adjust for potential confounding and identify factors that were associated with the outcome, all significant variables in the bivariable analyses were considered in the full multivariable model. With the drug use patterns being forced into the model, a backwards model selection procedure was used to identify the multivariate model with the best overall fit as indicated by the lowest quasilikelihood under the independence model criterion value. All statistical analyses were performed using the SAS software version 9.3 (SAS, Cary, NC). All p-values are two-sided.

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