Table Of ContentAssociation between stress and antiretroviral therapy adherence among
women living with HIV in Toronto, Ontario: Assessment of correlates,
mediation and moderation
By
Anita C. Benoit
A thesis submitted in conformity with the requirements
for the degree of Master of Science
Health Service Research
Health Services Outcomes and Evaluation
Institute of Health Policy, Management and Evaluation
University of Toronto
© Copyright by Anita C. Benoit, 2015
Association between stress and antiretroviral therapy adherence among
women living with HIV in Toronto, Ontario: Assessment of correlates,
mediation and moderation
Anita C. Benoit
Master of Science
Health Service Research
Health Services Outcomes and Evaluation
Institute of Health Policy, Management and Evaluation
University of Toronto
2015
Abstract
This cross-sectional study sought to: “Determine the association between stress, depression and
ART adherence among women living with and accessing care for HIV in Toronto, Ontario,
between 2007 and 2012”. Using OCS data, logistic regression models were used to identify
covariates of (≥95%) adequate adherence and mediators and moderators in the association between
stress and adherence. Among 307 women, 34.5% and 65.5% had poor and adequate adherence,
respectively. Women with poor versus adequate adherence had more reports of hazardous alcohol
use, stress events and depressive symptoms. No hazardous alcohol use (aOR=2.20, 95%CI:1.12-
4.32) and fewer stress events (aOR=0.56, 95%CI:0.33-0.94) were associated with increased odds
of adequate adherence. The association between environmental stress and adequate adherence was
attenuated among women ≤35 years (aOR=0.73, 95%CI:0.56-0.94) versus ≥45 years (aOR=0.51,
95%CI:0.34-0.77). Interventions to improve adherence and ensure levels ≥95% must address stress
and promote adaptive coping strategies to reduce or eliminate hazardous alcohol use.
ii
Acknowledgements
I would like to sincerely thank Dr. Mona Loutfy for her supervision and guidance.
I would also like to express a warm thanks to my thesis advisory committee members –Drs. Ann
Burchell, Janet Raboud and Kelly O’Brien – for their feedback and guidance on this project as
well as Drs. Sandra Gardner and Lucia Light for their invaluable guidance on statistical analysis.
I am grateful to all for being so generous with their time.
My gratitude also extends to the participants of the Ontario HIV Treatment Network (OHTN)
Cohort Study (OCS), who shared their information for the purposes of conducting research that
aims to improve the health and well-being of persons living with HIV.
I would also like to acknowledge the Canadian Institutes of Health Research (CIHR) for awarding
me with the IAPH Quantitative Research Fellowship (2012-2013) and the Aboriginal Research
Methodologies Fellowship (2013-2014), both of which enabled me to pursue this degree.
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Table of Contents
Abstract ........................................................................................................................................... ii
Acknowledgements ........................................................................................................................ iii
Table of Contents ........................................................................................................................... iv
List of Tables ................................................................................................................................ vii
List of Figures .............................................................................................................................. viii
List of Appendices ......................................................................................................................... ix
Abbreviations .................................................................................................................................. x
1. Background and Literature Review ........................................................................................ 1
1.1. Research Question ............................................................................................................ 1
1.2. Women and HIV .............................................................................................................. 1
1.2.1. HIV Prevalence and Incidence for Women .............................................................. 1
1.2.2. HIV Risk Factors for Women: Biology and Life Stressors ...................................... 2
1.3. Mental Health and HIV .................................................................................................... 6
1.3.1. Mental Health............................................................................................................ 6
1.3.2. Stress ......................................................................................................................... 6
1.3.3. Depression................................................................................................................. 7
1.4. Stress, Depression and HIV ............................................................................................. 9
1.4.1. HIV and Depression .................................................................................................. 9
1.4.2. Association between Stress and Depression for Women Living with HIV .............. 9
1.5. Antiretroviral Therapy.................................................................................................... 10
1.5.1. ART Adherence ...................................................................................................... 10
1.5.2. Healthy Service Utilization and ART Adherence ................................................... 13
1.5.3. ART Adherence and Stress ..................................................................................... 14
1.5.4. ART Adherence and Depression ............................................................................ 16
1.5.5. Women and ART Adherence .................................................................................. 17
2. Research Purpose and Objectives ......................................................................................... 18
2.1. Purpose ........................................................................................................................... 18
2.2. Specific Objectives ......................................................................................................... 18
3. Theoretical Framework ......................................................................................................... 20
3.1. Adherence Theoretical Framework ................................................................................ 20
3.2. Stress, Depression and Adherence Explained by the Modified Andersen-Newman
Framework ................................................................................................................................ 22
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4. Design and Methods ............................................................................................................. 25
4.1. The Ontario HIV Treatment Network Cohort Study ..................................................... 25
4.2. Project Study Design and Population ............................................................................. 25
4.3. Definition of Variables ...................................................................................................... 26
4.3.1. Socio-demographic, Psychosocial and Clinic Characteristics .................................... 26
4.3.2. Measuring Stress ......................................................................................................... 26
4.3.3. Measuring Depression ................................................................................................ 28
4.3.4. Measuring ART Adherence ........................................................................................ 29
4.3.5. Measuring Alcohol Use .............................................................................................. 30
4.3.6. Moderating Variables.................................................................................................. 31
4.4. Data Analysis ..................................................................................................................... 31
4.4.1. Descriptive Statistics ................................................................................................... 31
4.4.2. Sample Size Selection ................................................................................................. 32
4.4.3. Univariate and Multivariable Regression Analysis .................................................... 35
4.4.4. Regression Analysis for Testing Mediation and Moderation ..................................... 35
5. Results ................................................................................................................................... 38
5.1. Study Participant Characteristics ................................................................................... 38
5.2. Prevalence and Severity of Stress and Depression......................................................... 45
5.2.1. Describe Stress ........................................................................................................ 45
5.2.2. Describe the Psychosocial Characteristic, Stress Subscales and Items .................. 48
5.3. Prevalence and Severity of Depression as Measured using the CES-D ......................... 51
5.3.1. Describe Depression ............................................................................................... 51
5.4. Univariate and Multivariable Regression Analysis ........................................................ 52
5.5. Mediator and Moderator Effects .................................................................................... 56
5.5.1. Assess whether depression mediates the association between stress and adequate
adherence (Figure 1). ............................................................................................................ 56
5.5.2. Assess whether employment status, ethnicity, living alone or age at interview
moderate the association between stress and adequate adherence (Figure 2). ..................... 57
6. Conclusions ........................................................................................................................... 60
6.1. Discussions ..................................................................................................................... 60
6.1.1. Summary of Key Findings .......................................................................................... 60
6.1.2. Implication and Consequences of Stress and Depression on Adherence ................... 61
6.1.2.1. Stress and Stressors among Women Living with HIV and Accessing Care........ 61
6.1.2.2. Depression among women living with HIV accessing care ................................ 65
6.1.2.3. Hazardous alcohol use among women living with HIV accessing care .............. 67
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6.1.2.4. Addressing stress among women living with HIV .............................................. 69
6.1.2.5. Addressing hazardous alcohol use among women living with HIV .................... 72
6.1.2.6. Addressing depression among women living with HIV ...................................... 74
6.1.3. Adherence and Viral Load Proxies for Health Care Utilization ................................. 78
6.2. Future Research Using the OCS Data ................................................................................ 79
6.3. Considerations for Analysis ............................................................................................... 82
6.4. Research with the OCS: Merits and Limitations ............................................................... 84
7. Knowledge Translation and Exchange Plan ......................................................................... 86
7.1. Community Engagement ................................................................................................ 86
7.2. Knowledge Translation and Exchange ........................................................................... 87
References ..................................................................................................................................... 89
Appendix A. National Population Health Survey – Stress Questionnaire. ................................. 111
Appendix B. Center for Epidemiologic Studies Depression Scale. ............................................ 114
Appendix C. Adult Clinical Trials Group (ACTG) Adherence Follow-Up Questionnaire. ....... 116
Appendix D. Assessment of the linearity of the association between stress and adherence. ..... 119
1. Linearity of the association between stress and the logit of adherence with 6 groups (A)
and 10 groups (B) for the stress variable (recent life events/ specific chronic stress). ........... 119
2. Linearity of the association between stress and the logit of adherence with 6 groups (A)
and 10 groups (B) for the stress variable (recent life events/ general chronic stress). ........... 120
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List of Tables
Table 1. ART adherence: Cross-tabulation of missed medication responses to the ACTG
questions. ...................................................................................................................................... 33
Table 2. Power calculation to detect a difference in stress score as a continuous variable. ......... 34
Table 3. Baseline socio-demographic, psychosocial and clinic characteristics at last interview
(n=307). ......................................................................................................................................... 39
Table 4. Antiretroviral therapy characteristics at last interview (n=307). .................................... 42
Table 5. Comparison of socio-demographic, psychosocial and clinical characteristics between
women with poor and adequate ART adherence. ......................................................................... 43
Table 6. Comparison of psychosocial measures between women with poor and adequate ART
adherence. ..................................................................................................................................... 47
Table 7. Differences in the specific sources of stress between women having poor and adequate
ART adherence. ............................................................................................................................ 49
Table 8. Univariate and multivariable logistic regression models with outcomes for adequate
adherence. ..................................................................................................................................... 53
Table 9. Multivariable logistic regression models for viral load and health service visit. ........... 55
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List of Figures
Figure 1. Hypothesized mediated association between stress, depression and ART adherence
(objective #5a) and role for moderators between stress and ART adherence (objective #5b). .... 19
Figure 2. Conceptual framework for adherence modified from the Andersen and Newman
Framework of Health Service Utilization (191) (objective #5b). ................................................. 24
Figure 3. Mediation model. ........................................................................................................... 36
Figure 4. Model depicting depression (A) and hazardous alcohol use (B) as mediators of total
stress (RLE/OP-GCS) to adherence. ............................................................................................. 58
Figure 5. Moderator variables involved in the association between stress and adherence. .......... 59
viii
List of Appendices
Appendix A. National Population Health Survey – Stress Questionnaire. ................................. 111
Appendix B. Center for Epidemiologic Studies Depression Scale. ............................................ 114
Appendix C. Adult Clinical Trials Group (ACTG) Adherence Follow-Up Questionnaire. ....... 116
Appendix D. Assessment of the linearity of the association between stress and adherence. ..... 119
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Abbreviations
ACTG AIDS Clinical Trial Group
AIDS Acquired Immunodeficiency Syndrome
AOR Adjusted Odds Ratio
ART Antiretroviral Therapy
ASO AIDS Service Organization
AUDIT Alcohol Use Disorders Identification Test
CCHS Canadian Community Health Survey
CES-D Center for Epidemiological Studies Depression
CI Confidence Interval
DSM-V Diagnostic and Statistical Manual of Mental Disorders, Fifth Editio n
ECA Early Childhood Adversities
EI Entry Inhibitors
GCS General Chronic Stress
HIV Human Immunodeficiency Virus
IE Indirect Effect
II Integrase Inhibitors
IQR Interquartile Range
MOS SSS Medical Outcomes Study Social Support Survey
NNRTI Non-Nucleoside Reverse Transcriptase Inhibitors
NPHS National Population Health Survey
OCS OHTN Cohort Study
OHTN Ontario HIV Treatment Network
OP Ongoing Problems
x
