Mark V. Bradley, M.D.
Research Fellow, HIV Center for Clinical
and Behavioral Studies, NewYork State
Psychiatric Institute and Columbia
HIV Center for Clinical and
Grand Rounds June 26, 2008
The effectiveness of antiretroviral
regimens depends upon high levels of
Treatment failure is predicted by poor
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
• Access to care
• Financial resources
Medication Regimen Characteristics
• Complexity/Pill burden
• Side effects
• Education and health literacy
• Physical symptoms
• Use of avoidant coping strategies
• Health beliefs
• Psychiatric symptoms/disorders
Substance use disorders
Intravenous drug use
Cocaine use including crack
Problem alcohol use
“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
Depression is a robust
a range of studies and
Most of these studies
rather than categorical
Wagner et al, J Clin Epidemiol, 2001. 54 Suppl 1: p.
Palepu et al, substance abuse treatment. Addiction,
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Barfod et al AIDS Patient Care STDS, 2005. 19(5): p.
Ammassari A., et al., Psychosomatics, 2004. 45(5):
Arnsten et al, J Gen Intern Med, 2002. 17(5): p. 377-
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. 413-
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
has also found that
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 meta-
analysis. Psychosom Med, 2004. 66(6):
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
• The symptom threshold for adherence problems is
• The time from depression response to adherence
improvement is not known.
• The specific components of depression
symptomatology responsible for adherence failures
are not known.
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
• Chesney’s ACTG Follow-Up Questionnaire for
Adherence to Antiretroviral Medications
• Visual Analog Scale
• Pill Count
• Viral load
• Hamilton Depression Scale
• Depression Module of the SCID
Substance use: HIV Center Substance Use
Questionnaire (potential depression-
• Rey Verbal Learning Test
• WAIS Letter-Number Sequence
• Color Trails A and B
• Controlled Oral Word Association
• WAIS Test of Adult Reading
Follow up assessment 1
module of SCID
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
Recruitment procedures commenced in November,
Recruitment represented a major challenge to this
The intersection of specific eligibility criteria in several
domains resulted in many patients being screened out
of the study:
• 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
9 participants recruited to date
Gender 5 men
White 3 33
More than one 2 22
Unmployed 8 89
4 participants have completed to date.
• These subjects have overall demonstrated some
evidence of improvement in adherence which
occurred alongside improvements in depression
2 participants have not followed up after
baseline due to re-emergent, severe
substance use problems
3 participants remain in the process of data
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
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
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.).
Robert H. Remien, PhD
Judith G. Rabkin, PhD
Milton Wainberg, MD
Cheng-Shiun Leu, PhD
HIV Center Expertise
Patricia Warne, PhD
Katherine Elkington, PhD
Elizabeth Arias, MA
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
Todd P. Loftus, MD
Joseph F. Murray, MD