Mark V. Bradley, M.D.
Research Fellow, HIV Center for Clinical
and Behavioral Studies, New York State
Psychiatric Institute and Columbia
University
HIV Center for Clinical and
Behavioral Studies
Grand Rounds June 26, 2008
The effectiveness of antiretroviral
regimens depends upon high levels of
patient adherence.
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Treatment failure is predicted by poor
adherence
High levels of adherence are required to ensure
virologic suppression and prevent resistant
strains (varies by regimen class type).
Most studies show that 40-60% of patients are
less than 90% adherent
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Structural
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Housing
Access to care
Financial resources
Transportation
Medication Regimen Characteristics
• Complexity/Pill burden
• Side effects
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Individual-level factors
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Education and health literacy
Physical symptoms
Use of avoidant coping strategies
Health beliefs
Psychiatric symptoms/disorders
 Substance
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use disorders
Intravenous drug use
Marijuana
Cocaine use including crack
Problem alcohol use
Methamphetamine
 “Serious
mental illness”: psychotic illnesses
and bipolar disorder
 Anxiety
disorders including PTSD
 Depressive
symptoms / disorders
 High
prevalence of depressive disorders
in HIV+ samples
 Depression
predicts poorer medical
outcomes in HIV (Clinical progression,
mortality), even after controlling for
adherence
Depression is a robust
predictor of
nonadherence across
a range of studies and
methodologies
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Most of these studies
have examined
depression symptoms
rather than categorical
diagnoses.
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Wagner et al, J Clin Epidemiol, 2001. 54 Suppl 1: p.
S91-8.
Palepu et al, substance abuse treatment. Addiction,
2004. 99(3): p. 361-8.
Barfod et al AIDS Patient Care STDS, 2005. 19(5): p.
317-25.
Ammassari A., et al., Psychosomatics, 2004. 45(5):
p. 394-402.
Arnsten et al, J Gen Intern Med, 2002. 17(5): p. 37781.
Blanco et al, AIDS Res Hum Retroviruses, 2005.
21(8): p. 683-8.
Boarts et al, AIDS Behav, 2006.
Carrieri et al., Int J Behav Med, 2003. 10(1): p. 1-14.
Catz et al., Health Psychol, 2000. 19(2): p. 124-33.
Gonzalez et al, Health Psychol, 2004. 23(4): p. 4138.
Gordillo, et al Aids, 1999. 13(13): p. 1763-9.
Murphy et al., Arch Pediatr Adolesc Med, 2005.
159(8): p. 764-70.
Holzemer et al., AIDS Patient Care STDS, 1999.
13(3): p. 185-97.
Reynolds et al., AIDS Behav, 2004. 8(2): p. 141-50.
Tucker et al., Am J Med, 2003. 114(7): p. 573-80.
Waldrop-Valverde et al, Patient Care STDS, 2005.
19(5): p. 326-34.
Cardiac disease and
diabetes research
has also found that
depression predicts
poor medication
adherence
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Gehi, A., et al., Depression and
medication adherence in outpatients
with coronary heart disease: findings
from the Heart and Soul Study. Arch
Intern Med, 2005. 165(21): p. 2508-13.
Kalsekar, I.D., et al., Depression in
patients with type 2 diabetes: impact
on adherence to oral hypoglycemic
agents. Ann Pharmacother, 2006.
40(4): p. 605-11.
Lustman, P.J. and R.E. Clouse,
Depression in diabetic patients: the
relationship between mood and
glycemic control. J Diabetes
Complications, 2005. 19(2): p. 113-22.
Barth, J., M. Schumacher, and C.
Herrmann-Lingen, Depression as a
risk factor for mortality in patients with
coronary heart disease: a metaanalysis. Psychosom Med, 2004. 66(6):
p. 802-13.
Two studies provide retrospective evidence
that treatment of depression improves
adherence in HIV+ populations (Yun et al,
JAIDS 2005; Cook et al, AIDS Care 2006)
Research in other medical illnesses (diabetes,
cardiocascular disease) have suggested
prospectively and retrospectively that treating
depression may improve adherence (Lustman,
Arch Gen Psychiatry 2006; Katon et al, Arch
Intern Med 2005 )
•
To date, no published prospective research has
demonstrated that treating depression improves
adherence in HIV-positive depressed, nonadherent
medical patients.
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The symptom threshold for adherence problems is
not known.
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The time from depression response to adherence
improvement is not known.
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The specific components of depression
symptomatology responsible for adherence failures
are not known.
 Naturalistic
design
 Following depressed, antiretroviral
nonadherent HIV+ clinic patients who
have recently started or optimized
treatment for depression
 Monitoring their depressive symptoms
and antiretroviral adherence as they
continue antidepressant treatment.
 HIV+
adult patients
 Referred to study based on history of
depression and/or nonadherence
 Recent initiation or change in antidepressant
treatment (medication switch, titration, or
augmentation) or initiation of psychotherapy
 Followed in one of three HIV medical or
mental health clinics at Columbia Med Ctr.,
or the Center for Special Studies at Cornell.
 Currently
on antiretrovirals
 Meet the criteria for Major Depressive
Disorder, Minor Depressive Disorder, or
Dysthymic Disorder (SCID)
 Demonstrates <80% adherence at baseline
 Does not meet criteria for substance use
disorder in the past month
 Fluent in English
 No h/o bipolar disorder
 Adherence :
• Chesney’s ACTG Follow-Up Questionnaire for
Adherence to Antiretroviral Medications
• Visual Analog Scale
• Pill Count
• Viral load
 Depression :
• Hamilton Depression Scale
• Depression Module of the SCID
 Substance
use: HIV Center Substance Use
Questionnaire (potential depressionnonadherence mediator)
 Cognition:
• Rey Verbal Learning Test
• WAIS Letter-Number Sequence
• Stroop
• Color Trails A and B
• Controlled Oral Word Association
• WAIS Test of Adult Reading
Assessment Baseline
Time
assessment
(0 weeks)
Follow up assessment 1
(4 weeks)
Follow up
assessment 2
(8 weeks)
Measures
-Adherence
measures
-Adherence
measures
-Substance use
questionnaire
-Substance use
questionnaire
-HAM-D
-HAM-D
-Depression module
of SCID
-Depression
module of SCID
-SCID
-Adherence
measures
-HAM-D
-Substance use
Questionnaire
-Demographics
-Brief Cognitive
Battery
-Brief Cognitive
Battery
Linear regression models to examining
associations between changes in adherence scores
and changes in HAM-D scores, controlling for
substance use at each time point.
 Generalized estimating equations will be used to
account for within-subject correlation across the
three time points.
 In secondary analyses, we will examine
relationships between specific depression
symptoms (such as depressed mood, insomnia,
and anergia) and adherence
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Recruitment procedures commenced in November,
2007
Recruitment represented a major challenge to this
study
The intersection of specific eligibility criteria in several
domains resulted in many patients being screened out
of the study:
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Depressive disorder
<80% adherent in past 4 days - 1 week
Recent onset/change in depression treatment
Fluent in English
Not actively using substances
No history of bipolar disorder
No psychotic symptoms
 Many
patients identified and treated for
depression demonstrate good adherence
 Many
patients systematically identified
as nonadherent by their clinicians also
demonstrate other exlusionary features,
especially active substance use and
comorbid psychopathology
9 participants recruited to date
N
Gender
%
5 men
4 women
56
44
AfricanAmerican
4
44
White
3
33
More than one
2
22
Inclusion
diagnosis
6 MDD
3 Dysthymic
66
33
Sexual
orientation
5 straight
4 gay
56
44
Unmployed
8
89
Ethnicity
mean
Baseline 21-item
Hamilton
13.67
Baseline
Adherence
69.3
range
3-22
52.5-80.5
4
participants have completed to date.
• These subjects have overall demonstrated some
evidence of improvement in adherence which
occurred alongside improvements in depression
scores
2
participants have not followed up after
baseline due to re-emergent, severe
substance use problems
 3 participants remain in the process of data
collection
Baseline
Subject HAM- ADH
D
%
1
11
67.5
2
13
64.1
3
20
52.5
4
10
80.5
Means
13.5
4 weeks
HAM- ADH
D
%
2
81.5
9
95
10
98
7
90.5
66.3 7
91.3
Dep
Dx
None
None
None
MDD
8 weeks
HAM- ADH
D
%
3
67.3
15
95
4
100
3
100
6.25
90.6
Dep
Dx
None
None
None
None
 Depressed, nonadherent
HIV-positive
patients demonstrate a degree of
psychosocial complexity and comorbidity
that makes recruitment challenging.
 Studies
designed to examine this population
may require a degree of “tolerance” for this
complexity, rather than highly restrictive
eligibility criteria
 When
substance use disorders are not an
active issue, individual cases suggest that
treating depressive disorders may be one
method for improving adherence in depressed
patients
 Future
research will require larger samples and
longer follow-up periods in order to elucidate
relationships between depression treatment
and adherence changes.

This study has been funded by the HIV Center’s Pilot Studies Program and
by the Columbia Department of Psychiatry Frontier Fund.

Dr. Bradley is supported by a training grant from NIMH (T32 MH19139;
Behavioral Sciences Research in HIV Infection; Principal Investigator,
Anke A. Ehrhardt Ph.D.; Training Director: Theo Sandfort, Ph.D.).

The HIV Center for Clinical and Behavioral Studies at the New York State
Psychiatric Institute and Columbia University is supported by a grant from
NIMH (P30-MH43520; Principal Investigator: Anke A. Ehrhardt Ph.D.).
Mentor
Robert H. Remien, PhD
Study Advisors
Judith G. Rabkin, PhD
Milton Wainberg, MD
Cheng-Shiun Leu, PhD
HIV Center Expertise
Patricia Warne, PhD
Katherine Elkington, PhD
Research Assistant
Elizabeth Arias, MA
Harkness-6
Karen Brudney, MD
Noga Shalev, MD
Anne Skomorowsky, MD
Lucy Ann Wicks Clinic
Joan Storey, PhD
Vera Smith, PhD
Alexandra Bloom, PhD
Elizabeth Wade, PhD
Center for Special
Studies
Todd P. Loftus, MD
Joseph F. Murray, MD