Elsevier

The Lancet HIV

Volume 3, Issue 11, November 2016, Pages e529-e538
The Lancet HIV

Articles
Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial

https://doi.org/10.1016/S2352-3018(16)30053-4Get rights and content

Summary

Background

Depression is highly prevalent in people with HIV and has consistently been associated with poor antiretroviral therapy (ART) adherence. Integrating cognitive behavioural therapy (CBT) for depression with adherence counselling using the Life-Steps approach (CBT-AD) has an emerging evidence base. The aim of this study was to test the efficacy of CBT-AD.

Methods

In this three-arm randomised controlled trial in HIV-positive adults with depression, we compared CBT-AD with information and supportive psychotherapy plus adherence counselling using the Life-Steps approach (ISP-AD), and with enhanced treatment as usual (ETAU) including Life-Steps adherence counselling only. Participants were recruited from three sites in New England, USA (two hospital settings and one community health centre). Patients were randomly assigned (2:2:1) to receive CBT-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), ISP-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), or ETAU (one Life-Steps session and five assessment visits roughly every 2 weeks), randomisation was done with allocation software, in pairs, and stratified by three variables: study site, whether or not participants had been prescribed antidepressant medication, and whether or not participants had a history of injection drug use. The primary outcome was ART adherence at the end of treatment (4 month assessment) assessed via electronic pill caps (Medication Event Monitoring System [MEMS]) with correction for pocketed doses, analysed by intention to treat.

Findings

Patients were recruited from Feb 26, 2009, to June 21, 2012. Patients who were assigned to CBT-AD (94 randomly assigned, 83 completed assessment) had greater improvements in adherence (estimated difference 1·00 percentage point per visit, 95% CI 0·34 to 1·66, p=0·003) and depression (Center for Epidemiological Studies depression [CESD] score estimated difference −0·41, −0·66 to −0·16, p=0·001; Montgomery-Asberg depression rating scale [MADRS] score −4·69, −8·09 to −1·28, p=0·007; clinical global impression [CGI] score −0·66, −1·11 to −0·21, p=0·005) than did patients who had ETAU (49 assigned, 46 completed assessment) after treatment (4 months). No significant differences in adherence were noted between CBT-AD and ISP-AD (97 assigned, 87 completed assessment). No study-related adverse events were reported.

Interpretation

Integrating evidenced-based treatment for depression with evidenced-based adherence counselling is helpful for individuals living with HIV/AIDS and depression. Future efforts should examine how to best disseminate effective psychosocial depression treatments such as CBT-AD to people living with HIV/AIDS and examine the cost-effectiveness of such approaches.

Funding

National Institute of Mental Health, National Institute of Allergy and Infectious Diseases.

Introduction

Depression is a distressing illness that interferes with activities of daily life, is highly comorbid with HIV/AIDS, and is associated with worse adherence to antiretroviral therapy (ART),1 potentially affecting long-term immune function.2, 3 The less than optimal (albeit statistically significant) effects seen in previous studies of interventions to promote adherence might result from the effects of psychosocial problems such as depression.4

Integrating cognitive behavioural therapy (CBT) for adherence with CBT for depression (CBT-AD) has an emerging evidence base on both adherence and depression outcomes from a small (n=45) randomised controlled crossover trial in people living with HIV/AIDS in HIV care,5 an efficacy trial (n=89) of people with a history of injection drug use in drug abuse treatment,6 a pilot trial on the border between Mexico and the USA,7 and a pilot trial in South Africa.8 These studies generally used an enhanced treatment as usual control comparison and had few follow-up data,5, 6, 7 had a within-subjects design, or were initial studies with small samples.8 The present study extends previous work, with the primary aim of assessing CBT-AD in a full-scale efficacy trial of people in HIV care in three HIV treatment sites. We used a three-arm design so that the effects of the specific psychosocial treatment for adherence and depression (CBT-AD) could be compared with a time-matched alternative psychosocial treatment for depression and adherence (ie, information and supportive psychotherapy with adherence counselling [ISP-AD]), and with an enhanced treatment as usual with adherence counselling (ETAU). ETAU was included so that the intervention could be compared with what enhanced standard of care might be able to offer, without an intense and more costly intervention.

Research in context

Evidence before this study

Clinical depression is highly prevalent (approximately 37%) in individuals living with HIV and is associated with non-adherence to antiretroviral therapy. Cognitive behavioural therapy is a well studied non-pharmacological therapy treatment for depression. However, there is a general scarcity of efficacy studies on psychosocial treatments for depression and adherence in individuals living with HIV. We searched PubMed and PsycINFO, with the search terms “HIV and depression treatment”, “HIV and CBT”, “HIV and behaviour therapy”, and “HIV and psychological treatment” for papers published until about January, 2008, and at various timepoints during the study planning phases, and also monitored emerging studies during this trial.

Added value of this study

In this study, we found that for people living with HIV who have a clinical diagnosis of depression, 12 sessions of counselling integrating cognitive behavioural therapy for depression with a cognitive behavioural approach to enhance antiretroviral medication adherence (Life-Steps), was more effective than a single session of adherence counselling and a letter to the patient's treatment provider documenting the patient's depression. These gains were evident at the end of treatment (roughly 4 months), and over 8 months and 12 months of follow-up. This approach was not superior, however, to another manualised 12 session treatment for depression (information with supportive psychotherapy) that also integrated the same cognitive behavioural approach to adherence counselling. The findings in this study support the integration of cognitive behavioural adherence counselling (Life-Steps) into evidenced-based psychosocial treatments for depression. Accordingly, mental health-care providers who treat patients living with HIV might wish to integrate this counselling into their treatment to improve adherence to antiretroviral therapy, which might, in turn, improve HIV outcomes. These results support the preliminary findings from our group and extend them through a full-scale efficacy trial of HIV-positive individuals with depression in HIV care.

Implications of all the available evidence

Mental health-care providers should consider adding adherence counselling into their psychiatric treatment of patients with HIV who have comorbid depression and poor HIV medication adherence. Cost-effectiveness analyses are needed for policy implications because this study showed that a more intensive treatment for adherence and depression was more effective than a less intensive approach. Implementation and effectiveness trials are also needed.

Section snippets

Study design

This study was a three-arm, randomised controlled efficacy trial in three HIV clinics (two hospital based, one community health centre) in New England, USA. All procedures were reviewed and approved by the respective institutional review boards at Massachusetts General Hospital, Fenway Health, and The Miriam Hospital.

Participants

Eligible patients were those who were 18 years of age or older and HIV positive, had been prescribed ART for at least 2 months, and had either a current diagnosis of depression

Results

Patients were recruited between Feb 26, 2009, and April 12, 2012, with the 12 month follow-up period extending until April 29, 2013. 240 eligible patients were randomly assigned an intervention and included in the intention-to-treat analyses (figure 1). Attrition was lower than had been anticipated, so the ultimate sample sizes were greater than 80 in patients assigned to CBT-AD, 80 in patients assigned to ISP-AD, and 40 in patients assigned to ETAU. For 4 month outcomes, data were missing for

Discussion

In this study, CBT-AD outperformed ETAU on MEMS-based adherence at the end of the 4 month treatment period and over the subsequent 8 month follow-up, but did not outperform ISP-AD, a time-matched treatment for depression that integrated adherence counselling. Results from the 4 month assessment also favoured CBT with regard to depression outcomes compared with ETAU. These depression results were generally maintained over the follow-up period. Analyses that did not impute missing values revealed

References (30)

  • SA Safren et al.

    Life-steps: applying cognitive behavioural therapy to HIV medication adherence

    Cogn Behav Pract

    (1999)
  • SA Safren et al.

    Two strategies to increase adherence to HIV antiretroviral medication: life-steps and medication monitoring

    Behav Res Ther

    (2001)
  • JS Gonzalez et al.

    Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis

    J Acquir Immune Defic Syndr

    (2011)
  • A Alciati et al.

    Major depression-related immunological changes and combination antiretroviral therapy in HIV-seropositive patients

    Hum Psychopharmacol Clin Exp

    (2007)
  • G Ironson et al.

    Psychosocial and neurohormonal predictors of HIV disease progression (CD4 cells and viral load): a 4 year prospective study

    AIDS Behav

    (2015)
  • AJ Blashill et al.

    Mental health: a focus on stress, coping, and mental illness as it relates to treatment retention, adherence, and other health outcomes

    Curr HIV/AIDS Rep

    (2011)
  • SA Safren et al.

    A randomized controlled trial of cognitive behavioural therapy for adherence and depression (CBT-AD) in HIV-infected individuals

    Health Psychol

    (2009)
  • SA Safren et al.

    Cognitive behavioural therapy for adherence and depression (CBT-AD) in HIV-infected injection drug users: a randomized controlled trial

    J Consult Clin Psychol

    (2012)
  • JM Simoni et al.

    A preliminary RCT of CBT-AD for adherence and depression among HIV-positive Latinos on the U.S.–Mexico border: the Nuevo Día study

    AIDS Behav

    (2013)
  • LS Andersen et al.

    A pilot study of a nurse-delivered cognitive behavioral therapy intervention (Ziphamandla) for adherence and depression in HIV in South Africa

    J Health Psychol

    (2016)
  • K Kroenke et al.

    The Patient Health Questionnaire-2: validity of a two-item depression screener

    Med Care

    (2003)
  • M Saghaei

    Random allocation software for parallel group randomized trials

    BMC Med Res Methodol

    (2004)
  • U Simson et al.

    Psychotherapy intervention to reduce depressive symptoms in patients with diabetic foot syndrome

    Diabet Med

    (2008)
  • A Winston et al.

    Introduction to supportive psychotherapy

    (2004)
  • SA Safren et al.

    Coping with chronic illness: cognitive behavioural therapy for adherence and depression, therapist guide

    (2007)
  • Cited by (110)

    • Medical regimen adherence

      2023, Encyclopedia of Mental Health, Third Edition: Volume 1-3
    View all citing articles on Scopus
    View full text