Optimizing Management of HIV: Integrated Treatment for

Depression and Adherence

Focus area: Increasing

Adherence to HIV Medications

Life-Steps*• Psychoeducation/Motivation for

Adherence• Getting to Appointments• Communication with Treatment

Team• Coping with Side Effects• Obtaining Medications• Formulating a Daily Medication

Schedule

*Safren SA, Otto MW, Worth J. Life-Steps: Applying cognitive behavioral therapy to HIV medication adherence. Cogn Behav Pract. 1999;6:332-341.

• Storing Medications• Cue Control Strategies for Taking

Medication• Guided Imagery/Rehearsal• Handling Slips in Adherence• Review

Depression is Highly Prevalent

in Patients with HIV• Rates of depression among persons with HIV infection range from 20-37% in epidemiological and sample studies (Atkinson & Grant, 1994; Bing et al., 2001; Cruess et al., 2003)

• Depression is 2x more prevalent in patients with HIV than patients without HIV (Cielsa & Roberts, 2001)

Why Target Depression in an HIV Medication Adherence

Study?• Depression is associated with poor

medication adherence and accelerated disease progression (Pence et al., 2007; Safren et al., 2001)

• Depressed patients are 3x more likely to be non-adherent to medical treatment regimens than non-depressed patients (DiMatteo et al., 2000)

• Depression may moderate the ability of a patient to benefit from health-behavior interventions that do not address depression

• HIV adherence interventions for individuals with mental health disorders are lacking (Amico et al., 2006; Simoni et al., 2006)

CBT for Adherence and Depression (CBT-AD) in HIV

• Life-Steps (1 session)• Psychoeducation/Motivational

Interviewing about CBT for Depression (1 session)

• Behavioral Activation/Activity Scheduling (1 session)

• Adaptive thinking (3 sessions)

Each session builds on the previous session and each session integrates adherence skills.

• Problem Solving (3 sessions)

• Relaxation/Diaphragmatic Breathing (1 session)

Life-Steps*• Psychoeducation/Motivation for

Adherence• Getting to Appointments• Communication with Treatment

Team• Coping with Side Effects• Obtaining Medications• Formulating a Daily Medication

Schedule

*Safren SA, Otto MW, Worth J. Life-Steps: Applying cognitive behavioral therapy to HIV medication adherence. Cogn Behav Pract. 1999;6:332-341.

• Storing Medications• Cue Control Strategies for Taking

Medication• Guided Imagery/Rehearsal• Handling Slips in Adherence• Review

Play Video

Electronic Life Steps WorkbookCasey Claborn, M.S. Thad R. Leffingwell,. Ph.D.

Department of PsychologyOklahoma State University

1. Two arm RCT (full CBT versus LifeSteps and provider letter)

2. Cross over: those who still met initial inclusion criteria could cross over from comparison group after post

3. Outcome: Adherence (MEMs), Depression (Independent assessor, self-report)

CBT-AD: Study 1

>300 phone screens, 118 baseline evaluations

45 patients randomized (3 dropped post-randomization)

42 participants completed baseline and T229% AA, 15% Latino/Hispanic, 7% other; mean age = 44 64% had at least one additional DSM-IV diagnosis38% had two additional DSM-IV diagnoses

Most frequent comorbid diagnoses (includes participants with >1 comorbid diagnoses):

PTSD 13 (31%) ADHD 2 (5%)Social Phobia 9 (21%) OCD 2 (5%)

Panic disorder 11 (26%) GAD 2 (5%)

CBT-AD Study 1: Sample Issues

Study 1 Integrating the Treatment of Depression with Adherence Counseling

in HIV†

• 2 Arm, cross-over design comparing 12 sessions of CBT-AD to a single session of adherence counseling

• Participants: 45 randomized, 42 completers with DSM-IV diagnosable depression

• CBT-AD resulted in improved adherence (MEMS=pill cap) and depression at 3 months, and gains were maintained at 6 and 12 months.

• Those who “crossed over” caught up after completing the full intervention

HAM-D outcomes

0

5

10

15

20

25

BASE T2

†Safren SA, O’Cleirigh CO, Tan JY, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol. 2009;28:1-10.

F(1,42) = 6.32, p < .02, Cohen d = .82

MEMS Adherence outcomes

0

25

50

75

100

BASELINE T2CBT ETAU

F(1,42) = 21.94, p< .0001, Effect size (Cohen d) = 1.0

CBT-AD Study 2 Method• CBT for Medication Adherence and

Depression in HIV+ Methadone Patients o Participants recruited from methadone clinics and

community in Massachusetts and Rhode Islando Randomized to either ETAU or CBT-AD o Stratified by sex, depression severity (current MDD or

residual symptoms only), and adherence (baseline MEMS adherence above or below 80%)

• Inclusion Criteria:o HIV-positiveo Prescribed antiretroviral

therapyo History of injection drug use

and enrollment in a drug abuse treatment program for at least one month

o Current or subsyndromal depression

o Between the ages of 18 and 65

MeasuresClinician-

administered:• Mini International

Neuropsychiatric Interview (MINI; Sheehan et al., 1998)

• Montgomery-Asberg Depression Rating Scale (MADRS; Montgomery & Asberg, 1979)

• Clinical Global Impression (CGI; NIMH, 1985) for Depression and Substance Abuse Severity (1 = “Not at all ill” to 7 = “Extremely ill)”

Self-report:• Beck Depression

Inventory- Short Form (BDI-SF; Beck et al., 1961, 1988)

Biological Heath:• HIV plasma RNA viral

load• CD4+ lymphocyte count

MeasuresAdherence:• Electronic pill-cap

(Medication Event Monitoring System, MEMS; AARDEX)

• Monitored most frequently dosed or most difficult to remember

medication • Non-adherence defined as

missed dose or dose late by more than 2 hours

• Data corrected for pocketed doses, etc.

3 Month Assessment (n = 41)

Baseline Diagnostic Assessment (n = 154)

Baseline Independent Assessment

Life-Steps (n = 89) and Randomization

Excluded (n = 65)Did not meet inclusion criteria (n = 37)Dropped out (n = 28)

CBT-AD(n = 44)

CBT-AD(n = 45)

3 Month Assessment (n = 40)

6 Month Assessment (n = 35)

6 Month Assessment (n = 38)

12 Month Assessment (n = 36)

12 Month Assessment (n = 30)

Study Design &Participant Flow Diagram

Participants• 89 HIV-infected adults with a diagnosis of

depression in treatment for injection drug use were randomized– Sex and Age

• 61% men, mean age = 47 (SD = 7)– Substance Abuse Treatment

• 70% in methadone maintenance therapy, 6% in suboxone therapy, 24% in group or individual substance abuse therapy

– Employment• 66% on disability, 4% full-time work or school

– Race• 49% White, 32% Black

– Ethnicity• 25% self-identified as Hispanic or Latino

– Sexual Orientation• 79% exclusively heterosexual

– Disease Characteristics at Baseline• Mean CD4 = 449 (SD = 265), mean viral load = 3669 (SD

= 13808)– Exceptionally high psychiatric comorbidity

• 61% one additional DSM-IV diagnosis, 41% 2+There were no significant differences between conditions for any of these variables.

CBT-AD had greater acute adherence outcomes:

Longitudinal (HLM) Analysis of MEMS

65

70

75

80

85ETAUCBT-AD

Improvement in the CBT-AD condition was greater than in the ETAU condition (γslope = 0.717, t (87) = 2.01, p = .047).

Acute MEMS Adherence Outcomes

CBT-AD had Better Acute Depression Outcomes:

Longitudinal (HLM) Analysis of BDI-13

68

10121416 ETAU

CBT-AD

Trajectory of improvement in self-reported depression was greater for the CBT-AD condition than the ETAU condition (γslope = -0.30, t (87) = -2.60, p = .01).

Acute BDI Outcomes

CBT Had Better Clinician-Assessed Depression Outcomes: Analysis of CGI

& MADRS

2

3

4

5

Pre Randomization Post Treatment

Control

CBT-AD

15

17

19

21

23

25

27

29

31

Pre Randomization Post Treatment

ControlCBT-AD

F = 6.52, df (1,79), p < .01

Post Treatment MADRS Outcomes

Post Treatment CGI Outcomes

F = 14.77, df = (1,79), p < .001

Follow-up Adherence Gains in CBT-AD were not maintained after

treatment endedFollow Up MEMS Adherence

Outcomes

50

55

60

65

70

75

80

3 Month 6 Month 12 Month

CBT

ETAU

Significant decrease in medication adherence across the follow-up time period (γslope = -0.294, t (79) = -3.24, p < .01); and differences in adherence change over the follow up time period did not differ significantly between the conditions (γslope = 0.13, t (77) = -0.77, p = .44)

Depression Gains Were Maintained After Treatment

Ended• The significant decreases in MADRS scores for

the CBT-AD condition and non-significant decrease in the ETAU condition were maintained during the follow up period – A trend for a continuing decrease in depression

symptoms for the whole sample (γslope = -0.62, t (79) = -1.78, p = .08)

• The significant decreases in CGI scores for the CBT-AD condition and non-significant decrease in the ETAU condition were maintained during the follow up period– Continuing decrease in depression symptoms for the

whole sample (γslope = -0.10, t (79) = -2.29, p = .03)

Viral Load Did Not Differ by Study Condition at Follow Up: Repeated Measures (GLM) & Longitudinal

(HLM) Analysis• There were no significant differences

between the ETAU and CBT-AD conditions in HIV viral loadlog 10 at post treatment (F (1,87) = 0.168, p = .85)

• After controlling for resistance and HIV viral load at baseline, there was no significant change in viral loadlog 10 during the course of the study (γslope = -0.0015, t (84) = -0.801, p = .43) or significant differences between conditions (γslope = -.0016, t (81) = -0.450, p = .65) over the course of the study

CD4, However, Did Differ by Study Condition at Follow Up: Repeated Measures (GLM) & Longitudinal

(HLM) Analysis• There were no significant differences

between the ETAU and CBT-AD conditions in HIV viral loadlog 10 at post treatment (F (1,87) = 0.168, p = .85)

• After controlling for resistance and HIV viral load at baseline, there was no significant change in viral loadlog 10 during the course of the study (γslope = -0.590, t (79) = -1.08, p = .29).

• BUT there was a or significant differences between conditions (γslope = 2.09, t (76) = 2.20, p = .03) over the course of the study. This was a 61.2 DC4 cell increase compared to a 22.4 CD4 cell decrease

Conclusions• CBT-AD had acute and significant effects

on both adherence and depression during the intervention for triply diagnosed HIV-infected IDU

• Post-intervention discontinuation, adherence rates decreased but improvements in depression remained relatively stable

• Individuals struggling with multiple comorbidities, such as substance abuse and depression, may benefit from continued adherence counseling even after depression improves

• Integrated Life Steps Treatment Manuals

Thank YouCollaborators:• Dr. Kenneth Mayer• Dr. Roger Weiss• Dr. Deb Herman• Dr. Nafisseh

Soroudi• Dr. Robert Malow• Dr. Christina

Psaros• Dr. Andres Bedoya• Dr. Jonathan Lerner• Dr. Jeffrey

Gonzalez• Dr. Joseph Greer• Dr. Robert Knauz• Norma Reppucci• Joan Cremins• Susan Adams• Betty Bredin• Cal Dyer

Research Coordinators:

• Giselle Perez• Susie Michelson• Pamela Handelsman• Luis Serpa• Laura Reilly• Jared Israel• Jackie Bullis

NIDA Funding: R01 DA018603

The Participants!The Substance Abuse Treatment Clinics

Bay CoveHabit OpCoCSAC

Questions?