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. Author manuscript; available in PMC: 2016 Jan 1.
Published in final edited form as: AIDS Behav. 2015 Jan;19(1):120–127. doi: 10.1007/s10461-014-0847-3

High-intensity cannabis use and adherence to antiretroviral therapy among people who use illicit drugs in a Canadian setting

Gregory Slawson 1,2, M-J Milloy 1,3, Lynda Balneaves 2, Annick Simo 1, Silvia Guillemi 1, Robert Hogg 1,5, Julio Montaner 1,4, Evan Wood 1,4, Thomas Kerr 1,4
PMCID: PMC4289662  NIHMSID: NIHMS612745  PMID: 25012624

Abstract

Background

Cannabis is increasingly prescribed clinically and utilized by people living with HIV/AIDS (PLWHA) to address symptoms of HIV disease and to manage side effects of antiretroviral therapy (ART). In light of concerns about the possibly deleterious effect of psychoactive drug use on adherence to ART, we sought to determine the relationship between high-intensity cannabis use and adherence to ART among a community-recruited cohort of HIV-positive illicit drug users.

Methods

We used data from the ACCESS study, an ongoing prospective cohort study of HIV-seropositive illicit drug users linked to comprehensive ART dispensation records in a setting of universal no-cost HIV care. We estimated the relationship between at least daily cannabis use in the last six months, measured longitudinally, and the likelihood of optimal adherence to ART during the same period, using a multivariate linear mixed-effects model accounting for relevant socio-demographic, behavioral, clinical and structural factors.

Results

From May 2005 to May 2012, 523 HIV-positive illicit drug users were recruited and contributed 2430 interviews. At baseline, 121 (23.1%) participants reported at least daily cannabis use. In bivariate and multivariate analyses we did not observe an association between using cannabis at least daily and optimal adherence to prescribed HAART (Adjusted Odds Ratio = 1.12, 95% Confidence Interval [95% CI]: 0.76 – 1.64, p-value = 0.555.)

Conclusions

High-intensity cannabis use was not associated with adherence to ART. These findings suggest cannabis may be utilized by PLWHA for medicinal and recreational purposes without compromising effective adherence to ART.

Introduction

Since the introduction of antiretroviral therapy (ART), people living with HIV/AIDS (PLWHA) have experienced significant improvements in HIV-related morbidity and mortality (Lewden et al., 2012; Obel et al. 2011). Optimal adherence to ART has been shown to be strongly associated with virological suppression of plasma HIV-1 RNA viral load (pVL) and restoration of immunologic function (Cescan et al., 2011; May et al., 2006). However, despite these advances in HIV treatment, people who use illicit drugs (PWID) have frequently been found to exhibit sub-optimal adherence to ART and HIV/AIDS-related morbidity and mortality remains high in this population (Malta et al., 2008; Zwahlen et al., 2009; Larsen et al., 2010).

Among PLWHA, high-levels of sub-optimal adherence has been associated with ongoing active illicit drug use (Arnsten et al., 2002; Crisp et al., 2004; Hinklin et al., 2007; Lucas et al., 2001; Malta et al., 2008; Nolan et al., 2011; Palepu et al., 2006; Sharpe et al., 2004). Also, demographic characteristics and individual-level barriers to adherence among PWID include: age; female gender; alcohol use; lower self-efficacy; and psychiatric co-morbidities (Arnsten et al., 2007; Bouhnik et al., 2005; Carrieri et al., 2003; Hadland et al., 2012; Kerr et al., 2004; Tapp et al., 2011). Social and structural barriers to effective adherence, including homelessness and incarceration, have also been identified amongst drug users (Milloy et al., 2011; Milloy et al., 2012; Palepu et al., 2004; Palepu et al., 2011). Despite the risks active psychoactive drug use can pose for nonadherence to ART, few studies have evaluated the relationship of cannabis use on adherence to HIV treatment.

Cannabis is used frequently by PLWHA, with one observational study reporting 59% of PLWHA engaged in cannabis use in the past six months (Fogarty et al., 2007). PLWHA use cannabis to manage a number of HIV-related symptoms including anorexia, stress, nausea/vomiting, and pain (Prentiss et al., 2004; Ware et al., 2003; Woolridge et al., 2005). Despite the evidence to support the efficacy of cannabis in the amelioration of HIV-related symptoms (Abrams et al., 2003; Abrams et al., 2007; Ellis et al., 2009; Haney et al., 2007), the evidence regarding cannabis use and its possible impact on adherence is limited and we know of no long-term prospective studies assessing cannabis use as a factor that may affect adherence. Therefore, we conducted the present study to investigate the role cannabis use among a cohort of PWID living with HIV/AIDS in a setting with universal healthcare coverage to evaluate if cannabis use was detrimental to ART adherence.

Methods

Data for this study was obtained from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), an ongoing observational prospective cohort of HIV-positive illicit drug users. The study participants were recruited using community-based methods including snowball sampling and extensive outreach in Vancouver's Downtown Eastside (DTES) and among local HIV/AIDS service organizations. Following recruitment and the provision of informed consent, participants complete an extensive interviewer-administered questionnaire, provide a blood sample, and complete a nurse-administered questionnaire and examination. Follow-up occurs semi-annually. ACCESS recruitment is ongoing and includes the following criteria: individuals must be HIV-infected, aged 18 years or older, English speaking, and having used illicit drugs other than cannabinoids in the month prior to enrollment. ACCESS has been approved by the Providence HealthCare/University of British Columbia research ethics board.

Data from the semi-structured interviews is augmented with data on HIV care, ART medication exposure, and treatment/clinical outcomes obtained via a confidential linkage to the British Columbia Centre for Excellence in HIV/AIDS' Drug Treatment Program(BC-CfE), as described elsewhere (Wood et al., 2008). The BCCfE runs a centralized antiretroviral therapy dispensary for the province of British Columbia, and provides ART dispensing information on each participant in the ACCESS study. In addition to this, the program also contains an HIV/AIDS monitoring lab that provides full retrospective and prospective CD4+ cell count and plasma HIV-1 RNA viral load (pVL) observations for each participant in the study. Of note is the fact that all HIV care is provided free of charge to every PLWHA living in the province of BC, allowing us to analyze adherence to treatment free of the confounding influence of financial status.

Our main outcome, adherence to prescribed ART, was based on a pharmacy refill measure and was defined as the number of days ART was dispensed divided by the number of days the participant was eligible for ART in the previous six months. The outcome was further dichotomized into optimal adherence vs. sub-optimal adherence (≥95% vs. <95%). This validated measure using pharmacy refill data has been previously shown to be strongly associated with both virological suppression and survival (Palepu et al., 2001; Wood et al., 2003a; Wood et al., 2003c).

This study included all ACCESS participants who were exposed to ART at baseline and who had a CD4+ and viral load (pVL) observation within ±180 days of recruitment, and contributed at least one follow-up interview after the baseline interview. Individuals who initiated ART following recruitment were added and the date of the first interview following initiation was the baseline date. The primary explanatory variable of interest was high-intensity cannabis use, defined as at least daily self-reported cannabis use in the previous six-month period.

In order to estimate the relationship between high-intensity cannabis use and adherence to ART, we considered a number of secondary explanatory variables we hypothesized might confound this relationship including: age (per year older); gender (female vs. male); Aboriginal ancestry (yes vs. no); educational attainment (<high school diploma vs. >high school diploma) and formal employment in the previous six months (yes vs. no). The formal employment variable was defined, as in previous studies (Richardson, Wood, Li & Kerr, 2010), as having a regular job with a salary or temporary work in the six-month period prior to the interview. Individual-level and illicit drug use and related variables included; methadone maintenance therapy (yes vs. no); frequent cocaine injection (≥daily vs. <daily); frequent heroin injection (≥daily vs. <daily); frequent crack inhalation (≥daily vs.<daily) and daily binge alcohol use (>4 drinks per day-yes vs. no). We used the Center for Epidemiological studies Depression scale (CES-D) to measure depression. The variable was dichotomized (scores ≥16 vs. <16) with individuals who scored greater than 16 considered regarded as being depressed. The CES-D has been shown to be a reliable and valid indicator of mild to severe depression with a reliability rating of Cronbach's Alpha (0.85) (Low-Beer & Chan, 2000; Radloff, 1977).

Clinical variables included: CD4+ cell count (per 100 cells/mL); plasma HIV-1 RNA level (copies/mL, per log10 increase); time elapsed since HIV diagnosis (measured in months); a protease inhibitor (PI) as part of the ART regime (yes vs. no) at the time of ART initiation and HIV experience of the prescribing physician (less than six patients vs. ≥ six patients). The HIV experience of the prescribing physician was defined, as in previous studies (Sangsari et al., 2012), as the number of patients that the participant's prescribing physician had previously enrolled in the province-wide HIV treatment registry at the time of ART initiation for the participant. Additional structural variables found to influence ART adherence in similar populations were also included in the analysis including homelessness and incarceration (Milloy et al., 2011, Palepu et al., 2011). Homelessness was defined as living on the street or having no fixed address in the past six months (yes vs. no), and incarceration was defined as being in a detention centre, jail, prison or penitentiary overnight or longer at least once in the past 6 months (yes vs. no).

As an initial step, we compared selected demographic (age, gender, Aboriginal ancestry, education, formal employment, downtown eastside residency), behavioural (at least daily drug use including-injection heroin, injection cocaine, crack cocaine; binge drug use; binge alcohol use) and clinical (methadone maintenance, physician experience, HIV-1 viral load, CD4+ cell count) characteristics among those who did and did not report at least daily cannabis use at baseline. We tested for group differences using the χ2 test for categorical variables and the Wilcoxon rank-sum test for continuous variables.

Next we performed bivariate and multivariate generalized linear mixed-effects models to examine the association between the variables of interest and their impact on adherence to ART. This type of regression modelling was used to account for the correlation between data gathered over time from the same participant and to best estimate the independent effect of high-intensity cannabis use on the likelihood of non-adherence in each participant. After examining bivariate associations we constructed a multivariate model, designed using an a priori modelling strategy (Maldonado & Greenland, 1993). We fitted a multivariate model, which included our primary explanatory variable, with the full set of secondary explanatory variables, noting the value of the coefficient associated with ART adherence. Next, we utilized a stepwise approach and constructed reduced models, each model with one of the secondary explanatory variables removed from the full set of explanatory models. Through comparison of the value of the coefficient for the primary variable in the full model and the reduced models, we identified the secondary variable that resulted in the smallest relative change to the coefficient. We then removed this variable and continued with the comparisons. The process was continued until the maximum change for the value of the coefficient for ART adherence from the full model exceeded five percent. This type of modelling strategy has been utilized previously to best estimate the independent relationship between an outcome of interest with several selected confounding variables (Maldonado & Greenland, 1993; Marshall et al., 2009; Milloy et al., 2011).

Results

Between May 2005 and April 2012, 523 individuals were recruited who were ART-exposed, had complete clinical information and were eligible for the study. In the analytic sample 188 (36%) participants were female and 194 (37.1%) participants reported Aboriginal ancestry.

The baseline characteristics of the sample stratified by at least daily cannabis use are presented in Table 1. At baseline at least daily cannabis smokers were: younger (44.2 years vs. 46.6 years, p = 0.002); more likely to be male (17.8% vs. 5.36%; p< 0.001); more likely to have completed high school (14.7% vs. 8.4%; p = 0.04); and more likely to drink less than four alcohol drinks daily (15.7% vs. 7.5%; p = 0.004).

Table 1. Baseline characteristics of 523 ART-exposed illicit drug users stratified by at least daily cannabis use in the last six months, ACCESS study (n = 523).

Characteristic Less than daily cannabis use 402 (76.9) At least daily cannabis use 121 (23.1) p-value
Age
 Median 46.6 (40.1 – 50.2) 44.1 (37.8– 48.3) 0.002
Gender
 Male 241 (60.1) 93 (76.9)
 Female 160 (39.9) 28 (23.1) < 0.001
Aboriginal ancestry
 No 252 (62.7) 77 (63.6)
 Yes 150 (37.3) 44 (36.4) 0.849
Education
 < HS diploma 214 (53.2) 77 (63.6)
 ≥ HS diploma 188 (46.8) 44 (36.4) 0.043
Employment1
 No 339 (84.3) 104 (85.9)
 Yes 63 (15.7) 17 (14.1) 0.663
DTES resident1
 No 197 (49.0) 68 (56.2)
 Yes 205 (51.0) 53 (43.8) 0.165
MMT, current
 No 204 (50.8) 69 (57.1)
 Yes 198 (49.2) 52 (42.9) 0.225
Alcohol use4
 < 4 drinks/day 323 (80.3) 82 (67.8)
 ≥ 4 drinks/day 79 (19.7) 39 (32.2) 0.003
Heroin injection4
 < Daily 345 (85.8) 103 (85.1)
 ≥ Daily 57 (14.2) 18 (14.9) 0.847
Cocaine injection1
 < Daily 365 (90.8) 110 (90.9)
 ≥ Daily 37 (9.2) 11 (9.1) 0.969
Crack cocaine use1
 < Daily 244 (60.7) 80 (66.1)
 ≥ Daily 158 (39.3) 41 (33.9) 0.281
Binge drug use1
 No 315 (78.4) 101 (83.5)
 Yes 87 (21.6) 20 (16.5) 0.221
Adherence1
 < 95% 177 (44.03) 59 (48.8)
 ≥ 95% 225 (60.6) 62 (51.2) 0.359
CD4+ cell count
 Median (IQR) 2.9 (1.7 – 4.1) 2.9 (1.9 – 4.4) 0.569
Plasma HIV-1 RNA
 Median (IQR) 3.1 (1.6 – 4.4) 3.2 (1.6 – 4.4) 0.979
HIV MD experience
 Median (IQR) 52 (13 – 139) 51 (13 – 131) 0.859
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1

Refers to six month period prior to interview

Table 2 presents the bivariate associations between each explanatory variable and ART adherence over the study period. We did not observe a significant association between at least daily cannabis and ART adherence in a bivariate analysis (Odds Ratio [OR] = 0.91; 95% Confidence Interval [95% CI]: 0.63-1.30, p = 0.359). Female gender, homelessness, daily alcohol, daily heroin injection, daily cocaine injection, daily crack use, incarceration, and higher viral load were all negatively associated with optimal adherence in bivariate comparisons. Whereas older age, enrollment in MMT, ART regimes containing a PI, and higher CD4+ count were all positively associated with effective adherence to ART.

Table 2. Longitudinal bivariate and multivariate mixed-effects analyses of factors associated with ≥95% adherence to ART in the previous six months, ACCESS study (n = 523).

Characteristic OR1 95% CI2 p-value AOR3 95% CI2 p-value
Cannabis use (≥daily vs. less)4 0.91 0.63 – 1.30 0.618 1.12 0.76 – 1.64 0.555
Age (per year older) 1.07 1.04 – 1.10 < 0.001 0.98 0.95 – 1.01 0.351
Gender (Female vs. male) 0.57 0.37 – 0.88 0.010 0.76 0.51 – 1.13 0.186
Aboriginal ancestry (Yes vs. no) 0.50 0.32 – 0.76 0.70 0.70 0.47 – 1.03
Homeless (Yes vs. no) 0.44 0.28 – 0.71 < 0.001
Education (≥HS diploma vs. less 1.14 0.75 – 1.74 0.515
Alcohol (≥4 drinks vs. less)4 0.69 0.50 – 0.94 0.021 0.82 0.58 – 1.16 0.276
CM injection (≥daily vs. less)4 0.58 0.20 – 1.67 0.316
Heroin injection(≥daily vs. less) 4 0.33 0.21 – 0.49 < 0.001
Cocaine inject (≥daily vs. less)4 0.62 0.40 – 0.95 0.027
Crack use (≥daily vs. less)4 0.49 0.37 – 0.65 < 0.001
Incarceration (Yes vs. no)4 0.54 0.36 – 0.82 0.004
MMT (Yes vs. no) 2.65 1.91 – 3.68 < 0.001 1.49 1.08 – 2.06 0.015
CESD score (≥16 vs. <16) 0.98 0.70 – 1.35 0.902
Employment (Yes vs. no)4 1.25 0.86 – 1.73 0.254
Time since HIV (per month 1.00 0.99 – 1.00 0.954
Regimen includes PI (Yes vs. no) 11.71 8.30 – 16.50 < 0.001 6.41 4.62 – 8.88 < 0.001
CD4+ cells (Per 100 cells/mm3) 1.51 1.37 – 1.65 < 0.001
Plasma HIV RNA/mm3 (log10) 0.34 0.30 – 0.38 < 0.001 0.36 0.37 – 0.41 < 0.001
HIV MD (≥ 6 patients vs. less) 1.60 0.98 – 2.86 0.057
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1

Odds Ratio

2

95% Confidence Interval

3

Adjusted Odds Ratio

4

Refers to the six month period prior to the interview

Results from the multivariate model results can also be found on Table 2. After adjustment for pVL, ART regimen and engagement in MMT, high intensity cannabis use (Adjusted Odds ratio [AOR] 1.12; 95% CI: 0.76-1.64, p = 0.555) was not significantly associated with ART adherence.

Discussion

In this long-term longitudinal study of ART-exposed PWID, we did not observe a significant association between greater than daily cannabis use and ART adherence. Specifically, we did not find any evidence indicating that daily or more frequent cannabis use compromises effective HIV treatment. It has been previously shown that HIV-infected PWID who are able to achieve adherence levels ≥95% are able to derive the clinical benefis of HIV-1 RNA viral suppression and CD4+ cell count increases (Wood et al., 2003a; Wood et al., 2003b; Wood et al., 2003c)

Our finding specific to cannabis use and adherence is in line with a number of studies conducted among PLWHA. A cross-sectional study that examined symptom management, cannabis use and its association with adherence among 178 PLWHA in Northern California did not find a statistically significant association between cannabis use and adherence, while adherence was negatively associated with other forms of illicit drug and alcohol use (De Jong et al., 2005). In addition, among participants who experienced moderate to severe nausea, cannabis users were more likely than non-cannabis users to report effective adherence to ART. In other observational studies among convenience samples of PLWHA in Canada and the U.S., PLWHA have reported cannabis to be an effective medication for the amelioration of symptoms associated with HIV and ART side effects, with some users suggesting its use improves their adherence to ART (Prentiss et al., 2004;, Ware, et al., 2003). While we did not examine cannabis use for symptom management, these findings are similar to our results, where cannabis use did not significantly impact adherence. However, our results contradict those of a few studies that have found cannabis use to be associated with sub-optimal adherence to ART. A recent study that compared at least daily users, monthly users and non-users, found daily cannabis use to be associated with sub-optimal adherence and greater number of HIV-related symptoms (Bonn-Miller, Oser, Bucossi, & Traffton, 2012). The authors could not distinguish if sub-optimal adherence in the daily cannabis group was the result of a higher symptom burden or high intensity cannabis use and had inconsistent findings within their self-reported adherence measures. In a study of 775 PLWHA from Africa, Puerto Rico and the United States comparing cannabis use and over-the counter medications for symptom management amongst PLWHA, participants who reported cannabis use were more likely to self-report poor adherence (Corless et al., 2009). Another cross-sectional study of 200 PLWHA based in Australia, found that participants who reported cannabis use greater than 4 times per week had increased odds of poor adherence (Wilson, Doxanakis & Fairly, 2004). However, it should be noted that all of these studies were likely limited by their cross-sectional nature with a restricted number of possible confounding variables. In addition, in all of these studies adherence was measured by self-report, which has been found to be of limited validity (Kerr, Walsh, Lloyd-Smith & Wood, 2005; Kerr et al., 2008). To date, we are unaware of any other analysis that has examined high intensity cannabis use and adherence to ART longitudinally in a population of PWID who have free medication and healthcare access. We also utilized pharmacy refill data as a measure of adherence and consistent with our measure, optimal adherence was strongly associated with higher CD4+ cell counts and lower pVL.

Despite growing legal access to cannabis for PLWHA in Canada/North America and growing evidence of its effectiveness for symptom management in HIV care (Abrams et al., 2003; Abrams et al., 2007; Department of Justice Canada, 2011; Ellis et al., 2009; Haney et al., 2007) many healthcare practitioners remain reluctant to prescribe cannabis to patients (Belle-Isle & Hathaway, 2007). In order to support decisions to prescribe cannabis and cannabinoids, physicians will require additional evidence regarding the long-term impact of cannabis use on the health of cannabis users. Physicians may also have concerns about prescribing cannabis when its psychoactive effects, including transient confusion and short-term memory impairment, may impact the patient's ability to adhere to their medications. One study of PLWHA who use cannabis found among participants experiencing HIV symptoms there was an increase in memory impairment (Cristiani Pukay-Martin, & Bornstein, 2004). While our study did not analyze adherence and memory impairment, our findings suggest daily cannabis use may not compromise effective adherence. There also may be concerns amongst practitioners related to cannabis being utilized for recreational or non-intended purposes and the potential for psychological addiction with chronic use (Zvolensky et al., 2008). While concerns regarding inappropriate use and addiction have not been addressed here, our findings suggest at least daily cannabis use does not compromise adherence in a population who use illicit drugs. Given the high prevalence (23.1%) of at least daily cannabis use in our population, healthcare practitioners may also wish to engage PLWHA in discussions about addiction, harm reduction and cannabis use to ensure individuals are informed about potential negative impacts associated with the use of cannabis. Additional referrals to medical cannabis dispensaries, where ingestible forms of cannabis, and harm reduction education are available for clients, may be beneficial for frequent cannabis users. In addition, randomized trials of cannabis and cannabinoids are needed to fully understand their role in HIV symptom management and disease processes.

Our study may have limitations. First, we utilized a cohort with a history of illicit drug use that is comprised of individuals who live in a setting where access to ART medications and HIV care is free. As such, our finding may be limited to these individuals and not generalizable to different populations in other geographic areas. Our pharmacy refill measure may overestimate adherence in the sample, as it indicates the number of ART medications administered without capturing the actual ingestion of these medications. However, this measure has previously been shown to be an accurate predictor of virological suppression (Wood et al., 2003c) and in this study, it was strongly associated with improved immunological and virologic status. While we attempted to control for a number of potentially confounding variables, adherence to ART is extremely complex and, common to all observational studies, we cannot exclude the possibility of unmeasured confounding variables. Finally, we did not examine the impact of less than daily cannabis use for medical purposes or symptom management in PLWHA and ART adherence, which has been previously shown to have a positive association with improved adherence (De Jong et. al., 2005). Further studies that examine cannabis use patterns and symptom management amongst PLWHA may help determine if there are additional associated benefits of cannabis use and ART adherence.

In summary, we found almost a quarter of our ART-exposed PWID were at least daily cannabis users at baseline, and in a longitudinal analysis using a validated measure, high-intensity cannabis use was not associated with adherence to ART. These findings suggest cannabis may be utilized by PLWHA for medicinal and recreational purposes without compromising effective adherence to ART.

Acknowledgments

We thank the study participants for their contributions to the research, as well as current and past researchers and staff. We would specifically like to thank Deborah Graham, Tricia Collingham, Carmen Rock, Brandon Marshall, Caitlin Johnston, Steve Kain, Benita Yip, Jennifer Matthews and Kristie Starr for their research and administrative assistance. The study is supported by the US National Institutes of Health (R01-DA021525). This work was supported in part by a Tier 1 Canada Research Chair in Inner-City Medicine awarded to Dr. Wood. Dr. Milloy is supported by the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research.

References

  1. Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, Schambelan M. Short-term effects of cannabinoids in patients with HIV-1 infection: A randomized, placebo-controlled clinical trial. Annals of Internal Medicine. 2003;139(4):258. doi: 10.7326/0003-4819-139-4-200308190-00008. [DOI] [PubMed] [Google Scholar]
  2. Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Petersen KL. Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial. Neurology. 2007;68(7):515–521. doi: 10.1212/01.wnl.0000253187.66183.9c. [DOI] [PubMed] [Google Scholar]
  3. Arnsten J, Demas P, Grant R, Gourevitch M, Farzadegan H, Howard A, Schoenbaum E. Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. Journal of General Internal Medicine. 2002;17(5):377–381. doi: 10.1046/j.1525-1497.2002.10644.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bangsberg DR, Hecht FM, Charlebois ED, Zolopa AR, Holodniy M, Sheiner L, Moss A. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS (London, England) 2000;14(4):357–366. doi: 10.1097/00002030-200003100-00008. [DOI] [PubMed] [Google Scholar]
  5. Belle-Isle L, Hathaway A. Barriers to access to medical cannabis for canadians living with HIV/AIDS. AIDS Care. 2007;19(4):500–506. doi: 10.1080/09540120701207833. [DOI] [PubMed] [Google Scholar]
  6. Bonn-Miller MO, Oser ML, Buccosi MB, Trafton JA. Cannabis use and HIV antiretroviral therapy adherence and HIV-related symptoms. Journal of Behavioral Medicine. 2012 doi: 10.1007/s10865-012-9458-5. October 12, 2012. [Epub ahead of print] [DOI] [PubMed] [Google Scholar]
  7. Bouhnik AD, Preau M, Vincent E, Carrieri MP, Gallais H, Lepeu G, et al. Depression and clinical progression in HIV-infected DU treated with highly active antiretroviral therapy. Antiviral Therapy. 2005;10:53–61. [PubMed] [Google Scholar]
  8. Brion JM, Dawson Rose C, Nicholas PK, Sloane R, Voss JG, Corless IB, Willard S. Unhealthy substance-use behaviors as symptom-related self-care in persons with HIV/AIDS. Nursing & Health Sciences. 2011;13(1):16–26. doi: 10.1111/j.1442-2018.2010.00572.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carrieri MP, Chesney MA, Spire B, Loundou A, Sobel A, Lepeu G, Moatti JP. Failure to maintain adherence to HAART in a cohort of french HIV-positive injecting drug users. International Journal of Behavioral Medicine. 2003;10(1):1–14. doi: 10.1207/s15327558ijbm1001_01. [DOI] [PubMed] [Google Scholar]
  10. Cescon AM, Cooper C, Chan K, Palmer AK, Klein MB, Machouf N, Loutfy MR, Raboud J, Rachlis A, Ding E, Lima VD, Montaner JSG, Rourke SB, Smieja M, Tsoukas C, Hogg RS. Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site canadian cohort. HIV Medicine. 2011;12(6):352–360. doi: 10.1111/j.1468-1293.2010.00890.x. [DOI] [PubMed] [Google Scholar]
  11. Chesney MA, Morin M, Sherr L. Adherence to HIV combination therapy. Social Science & Medicine. 2000;50(11):1599–1605. doi: 10.1016/s0277-9536(99)00468-2. [DOI] [PubMed] [Google Scholar]
  12. Corless IB, Lindgren T, Holzemer W, Robinson L, Moezzi S, Kirksey K, Reynolds N. Marijuana effectiveness as an HIV self-care strategy. Clinical Nursing Research. 2009;18(2):172–193. doi: 10.1177/1054773809334958. [DOI] [PubMed] [Google Scholar]
  13. Crisp BR, Williams M, Timpson S, Ross MW. Medication compliance and satisfaction with treatment for HIV disease in a sample of african-american crack cocaine smokers. AIDS and Behavior. 2004;8(2):199–206. doi: 10.1023/B:AIBE.0000030250.33931.af. [DOI] [PubMed] [Google Scholar]
  14. Cristiani S, Pukay-Martin N, Bornstein B. Marijuana use and cognitive function in HIV-infected people. The Journal of Neuropsychiatry and Clinical Neurosciences. 2004;16(3):330–335. doi: 10.1176/jnp.16.3.330. [DOI] [PubMed] [Google Scholar]
  15. de Jong B, Prentiss D, McFarland W, Machekano R, Israelski D. Marijuana use and its association with adherence to antiretroviral therapy among HIV-infected persons with moderate to severe nausea. JAIDS: Journal of Acquired Immune Deficiency Syndromes. 2005;38(1):43–46. doi: 10.1097/00126334-200501010-00008. [DOI] [PubMed] [Google Scholar]
  16. Department of Justice Canada. Marihuana medical access regulations. 2011 Retrieved September 12, 2011, from http://lois-laws.justice.gc.ca/eng/regulations/SOR-2001-227/page-1.html.
  17. Ellis RJ, Toperoff W, Vaida F, van d B, Gonzales J, Gouaux B, Atkinson JH. Smoked medicinal cannabis for neuropathic pain in HIV: A randomized, crossover clinical trial. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. 2009;34(3):672–680. doi: 10.1038/npp.2008.120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fogarty A, Rawstorne P, Prestage G, Crawford J, Grierson J, Kippax S. Marijuana as therapy for people living with HIV/AIDS: Social and health aspects. AIDS Care. 2007;19(2):295–301. doi: 10.1080/09540120600841930. [DOI] [PubMed] [Google Scholar]
  19. Hadland SE, Milloy MJ, Kerr T, Zhang R, Guillemi S, Hogg R, Wood E. Young age predicts poor antiretroviral adherence and viral load suppression among injection drug users. AIDS Patient Care & STDs. 2012;26(5):274–280. doi: 10.1089/apc.2011.0196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Haney M, Gunderson EW, Rabkin J, Hart CL, Vosburg SK, Comer SD, Foltin RW. Dronabinol and marijuana in HIV-positive marijuana smokers: Caloric intake, mood, and sleep. JAIDS: Journal of Acquired Immune Deficiency Syndromes. 2007;45(5):545–554. doi: 10.1097/QAI.0b013e31811ed205. [DOI] [PubMed] [Google Scholar]
  21. Hinkin CH, Barclay TR, Castellon SA, Levine AJ, Durvasula RS, Marion SD, Longshore D. Drug use and medication adherence among HIV-1 infected individuals. AIDS and Behavior. 2007;11(2):185–194. doi: 10.1007/s10461-006-9152-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hogg RS, Bangsberg DR, Lima VD, Alexander C, Bonner S, Yip B, Harrigan PR. Emergence of drug resistance is associated with an increased risk of death among patients first starting HAART. Plos Medicine. 2006;3(9):e356–e356. doi: 10.1371/journal.pmed.0030356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hogg RS, Heath K, Bangsberg D, Yip B, Press N, O'Shaughnessy MV, Montaner JSG. Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. AIDS (London, England) 2002;16(7):1051–1058. doi: 10.1097/00002030-200205030-00012. [DOI] [PubMed] [Google Scholar]
  24. Kerr T, Marshall A, Walsh J, Palepu A, Tyndall M, Montaner J, Wood E. Determinants of HAART discontinuation among injection drug users. AIDS Care. 2005;17(5):539–549. doi: 10.1080/09540120412331319778. [DOI] [PubMed] [Google Scholar]
  25. Kerr T, Walsh J, Lloyd-Smith E, Wood E. Measuring adherence to highly active anteretroviral therapy: Implications for research and practice. Current HIV/AIDS Report. 2005;2(4):200–205. doi: 10.1007/s11904-005-0017-3. [DOI] [PubMed] [Google Scholar]
  26. Kerr T, Hogg RS, Yip B, Tyndall MW, Montaner J, Wood E. Validity of self-reported adherence among injection drug users. JIAPAC: Journal of the International Association of Physicians in AIDS Care. 2008;7(4):157–159. doi: 10.1177/1545109708320686. [DOI] [PubMed] [Google Scholar]
  27. Larsen MV, Omland LH, Gerstoft J, Larsen CS, Jensen J, Obel N, Kronborg G. Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population-based cohort study. Addiction. 2010;105(3):529–35. doi: 10.1111/j.1360-0443.2009.02827.x. [DOI] [PubMed] [Google Scholar]
  28. Lewden C, Bouteloup V, De Wit S, Sabin C, Mocroft A, Wasmuth JC, van Sighem A, Kirk O, Obel N, Panos G, Ghosn J, Dabis F, Mary-Krause M, Leport C, Perez-Hoyos S, Sobrino-Vegas P, Stephan C, Castagna A, Antinori A, dArminio Monforte A, Torti C, Mussini C, Isern V, Calmy A, Teira R, Egger M, Grarup J, Chêne Gl. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. International Journal of Epidemiology. 2012;41(2):433–45. doi: 10.1093/ije/dyr164. [DOI] [PubMed] [Google Scholar]
  29. Low-Beer S, Chan K. Depressive symptoms decline among persons on HIV protease inhibitors. JAIDS: Journal of Acquired Immune Deficiency Syndromes. 2000b;23(4):295. doi: 10.1097/00126334-200004010-00003. [DOI] [PubMed] [Google Scholar]
  30. Lucas GM, Cheever LW, Chaisson RE, Moore RD. Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection. JAIDS: Journal of Acquired Immune Deficiency Syndromes. 2001;27(3):251. doi: 10.1097/00126334-200107010-00006. [DOI] [PubMed] [Google Scholar]
  31. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. American Journal of Epidemiology. 1993;138(11):923–936. doi: 10.1093/oxfordjournals.aje.a116813. [DOI] [PubMed] [Google Scholar]
  32. Malta M, Strathdee SA, Magnanini MMF, Bastos FI. Adherence to antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome among drug users: A systematic review. Addiction (Abingdon, England) 2008;103(8):1242–1257. doi: 10.1111/j.1360-0443.2008.02269.x. [DOI] [PubMed] [Google Scholar]
  33. Marshall BD, Kerr T, Shoveller JA, Patterson TL, Buxton JA, Wood E. Homelessness and unstable housing associated with an increased risk of HIV and STI transmission among street-involved youth. Health & Place. 2009;15(3):753–760. doi: 10.1016/j.healthplace.2008.12.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. May MT, Sterne JAC, Costagliola D, Sabin CA, Phillips AN, Justice AC, Dabis F, Gill J, Lundgren J, Hogg RS, de Wolf F, Fätkenheuer G, Staszewski S, d'Arminio MA, Egger M. HIV treatment response and prognosis in europe and north america in the first decade of highly active antiretroviral therapy: A collaborative analysis. Lancet. 2006;368(9534):451–458. doi: 10.1016/S0140-6736(06)69152-6. [DOI] [PubMed] [Google Scholar]
  35. Miller CL, Strathdee SA, Spittal PM, Kerr T, Li K, Schechter MT, Wood E. Elevated rates of HIV infection among young aboriginal injection drug users in a canadian setting. Harm Reduction Journal. 2006;3:9. doi: 10.1186/1477-7517-3-9. 6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Milloy MJ, Kerr T, Buxton J, Rhodes T, Guillemi S, Hogg R, Wood E. Dose-response effect of incarceration events on nonadherence to HIV antiretroviral therapy among injection drug users. Journal of Infectious Diseases. 2011;203(9):1215–1221. doi: 10.1093/infdis/jir032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Milloy MJ, Kerr T, Bangsberg DR, Buxton J, Parashar S, Guillemi S, Wood E. Homelessness as a structural barrier to effective antiretroviral therapy among HIV-seropositive illicit drug users in a canadian setting. AIDS Patient Care & STDs. 2012;26(1):60–67. doi: 10.1089/apc.2011.0169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nolan S, Milloy M, Zhang R, Kerr T, Hogg RSG, Wood E. Adherence and plasma HIV RNA response to antiretroviral therapy among HIV-seropositive injection drug users in a canadian setting. AIDS Care. 2011;23(8):980–987. doi: 10.1080/09540121.2010.543882. [DOI] [PubMed] [Google Scholar]
  39. Obel N, Omland LH, Kronborg G, Larsen CS, Pedersen C, Pedersen G, Sorensen HT, Gerstoft J. Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on HAART: a population-based nationwide cohort study. PLoS ONE. 2011;6(7):e22698. doi: 10.1371/journal.pone.0022698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine. 1998;338(13):853–860. doi: 10.1056/NEJM199803263381301. [DOI] [PubMed] [Google Scholar]
  41. Palepu A, Tyndall MW, Joy R, Kerr T, Wood E, Press N, Montaner J. Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: The role of methadone maintenance therapy. Drug & Alcohol Dependence. 2006;84(2):188–194. doi: 10.1016/j.drugalcdep.2006.02.003. [DOI] [PubMed] [Google Scholar]
  42. Palepu A, Yip B, Miller C, Strathdee SA, O'Shaughnessy MV, Montaner JS, Hogg RS. Factors associated with the response to antiretroviral therapy among HIV-infected patients with and without a history of injection drug use. AIDS (London, England) 2001;15(3):423–424. doi: 10.1097/00002030-200102160-00021. [DOI] [PubMed] [Google Scholar]
  43. Palepu A, Milloy MJ, Kerr T, Zhang R, Wood E. Homelessness and adherence to antiretroviral therapy among a cohort of HIV-infected injection drug users. Journal of Urban Health. 2011;88(3):545–555. doi: 10.1007/s11524-011-9562-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Palepu A, Tyndall MW, Chan K, Wood E, Montaner JSG, Hogg RS. Initiating highly active antiretroviral therapy and continuity of HIV care: The impact of incarceration and prison release on adherence and HIV treatment outcomes. Antiviral Therapy. 2004;9(5):713–719. [PubMed] [Google Scholar]
  45. Prentiss D, Power R, Balmas G, Tzuang G, Israelski DM. Patterns of marijuana use among patients with HIV/AIDS followed in a public health care setting. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2004;35(1):38–45. doi: 10.1097/00126334-200401010-00005. [DOI] [PubMed] [Google Scholar]
  46. Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Applied Psychological Measurement. 1977;1(3):385–401. [Google Scholar]
  47. Richardson L, Wood E, Li K, Kerr T. Factors associated with employment among a cohort of injection drug users. Drug & Alcohol Review. 2010;29(3):293–300. doi: 10.1111/j.1465-3362.2009.00141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sangsari S, Milloy M, Ibrahim A, Kerr T, Zhang R, Montaner J, Wood E. Physician experience and rates of plasma HIV-1 RNA suppression among illicit drug users: An observational study. BMC Infectious Diseases. 2012;12(22) doi: 10.1186/1471-2334-12-22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sharpe TT, Lee LM, Nakashima AK, Elam-Evans L, Fleming PL. Crack cocaine use and adherence to antiretroviral treatment among HIV-infected black women. Journal of Community Health. 2004;29(2):117–127. doi: 10.1023/b:johe.0000016716.99847.9b. [DOI] [PubMed] [Google Scholar]
  50. Tapp C, Milloy M, Kerr T, Zhang R, Guillemi S, Hogg RS, Wood E. Female gender predicts lower access and adherence to antiretroviral therapy in a setting of free healthcare. BMC Infectious Diseases. 2011;11:86–86. doi: 10.1186/1471-2334-11-86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: Results of a nationwide survey. International Journal of Clinical Practice. 2005;59(3):291–295. doi: 10.1111/j.1742-1241.2004.00271.x. [DOI] [PubMed] [Google Scholar]
  52. Ware MA, Rueda S, Singer J, Kilby D. Cannabis use by persons living with HIV/AIDS: Patterns and prevalence of use. Journal of Cannabis Therapeutics. 2003;3(2):3–15. [Google Scholar]
  53. Wilson K, Doxanakis A, Fairley K. Predictors for non-adherence to antiretroviral therapy. Sexual Health. 2004;1(4):251–257. doi: 10.1071/sh04020. [DOI] [PubMed] [Google Scholar]
  54. Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy M, Montaner J. Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 × 10(9) cells/L. Annals of Internal Medicine. 2003a;139(10):810. doi: 10.7326/0003-4819-139-10-200311180-00008. [DOI] [PubMed] [Google Scholar]
  55. Wood E, Hogg RS, Lima VD, Kerr T, Yip B, Marshall BDL, Montaner JSG. Highly active antiretroviral therapy and survival in HIV-infected injection drug users. JAMA: The Journal of the American Medical Association. 2008;300(5):550–554. doi: 10.1001/jama.300.5.550. [DOI] [PubMed] [Google Scholar]
  56. Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JSG. Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy? AIDS (London, England) 2003b;17(5):711–720. doi: 10.1097/00002030-200303280-00009. [DOI] [PubMed] [Google Scholar]
  57. Wood E, Montaner JSG, Yip B, Tyndall MW, Schechter MT, O'Shaughnessy MV, Hogg RS. Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users. CMAJ: Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. 2003c;169(7):656–661. [PMC free article] [PubMed] [Google Scholar]
  58. Woolridge E, Barton S, Samuel J, Osorio J, Dougherty A, Holdcroft A. Cannabis use in HIV for pain and other medical symptoms. Journal of Pain & Symptom Management. 2005;29(4):358–367. doi: 10.1016/j.jpainsymman.2004.07.011. [DOI] [PubMed] [Google Scholar]
  59. Zvolensky MJ, Lewinsohn P, Bernstein A, Schmidt NB, Buckner JD, Seeley J, Bonn-Miller MO. Prospective associations between cannabis use, abuse, and dependence and panic attacks and disorder. Journal of Psychiatric Research. 2008;42(12):1017–1023. doi: 10.1016/j.jpsychires.2007.10.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Zwahlen M, Harris R, May M, Hogg R, Costagliola D, de Wolf F, Egger M. Mortality of HIV-infected patients starting potent antiretroviral therapy: Comparison with the general population in nine industrialized countries. International Journal of Epidimiology. 2009;38(6):1624–1633. doi: 10.1093/ije/dyp306. Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries. [DOI] [PMC free article] [PubMed] [Google Scholar]

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