The impact of mental health and traumatic life experiences on antiretroviral treatment outcomes for people living with HIV/AIDS

doi:10.1093/jac/dkp006

J Antimicrob Chemother. 2009 April; 63(4): 636–640.

Published online 2009 January 18. doi: 10.1093/jac/dkp006

PMCID: PMC2654041

Copyright © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

The impact of mental health and traumatic life experiences on antiretroviral treatment outcomes for people living with HIV/AIDS

Brian Wells Pence^*

Department of Community and Family Medicine, Duke Global Health Institute, and Center for Health Policy, Duke University, Durham, NC, USA

^*Tel: Phone: +1-919-613-6219; Fax: +1-919-684-6246; E-mail: bpence/at/aya.yale.edu

This article has been cited by other articles in PMC.

Abstract

Potent antiretroviral therapy (ART) has transformed HIV from a death sentence to a chronic illness. Accordingly, the goal of HIV care has shifted from delaying death to achieving optimal health outcomes through ART treatment. ART treatment success hinges on medication adherence. Extensive research has demonstrated that the primary barriers to ART adherence include mental illness, especially depression and substance abuse, as well as histories of traumatic experiences such as childhood sexual and physical abuse. These psychosocial factors are highly prevalent in people living with HIV/AIDS (PLWHA) and predict poor ART adherence, increased sexual risk behaviours, ART treatment failure, HIV disease progression and higher mortality rates. The efficacy of standard mental health interventions, such as antidepressant treatment and psychotherapy, has been well-defined, and a small but growing body of research demonstrates the potential for such interventions to improve ART adherence and reduce sexual risk behaviours. Despite this evidence, mental disorders in PLWHA frequently go undiagnosed and untreated. Challenges to the provision of mental healthcare for PLWHA in HIV clinical settings include time and resource constraints, lack of expertise in psychiatric diagnosis and treatment, and lack of available mental health referral services. Future research should prioritize the evaluation of mental health interventions that are cost-effective and feasible for widespread integration into HIV clinical care; the impact of such interventions on ART adherence and clinical outcomes; and interventions to identify individuals with histories of traumatic experiences and to elucidate the mechanisms through which such histories pose barriers to effective HIV treatment.

Keywords: mental illness, depression, trauma, adherence

Introduction

The introduction of increasingly potent combination antiretroviral treatment (ART) regimens over the past 12 years has dramatically reduced HIV-related morbidity and mortality in wealthy countries, with the life expectancy of HIV-infected patients on ART now approaching that of the general population.¹ With the transformation of HIV/AIDS from a practical death sentence to a chronic illness, the objective of HIV clinical care has increasingly focused on using ART to achieve sustained suppression of HIV RNA plasma levels and thereby optimize HIV health outcomes.

Health outcomes among people living with HIV/AIDS (PLWHA) on ART are heavily influenced by medication adherence. The levels of adherence required to prevent viral mutation and ART resistance are very high by the standards of other chronic illnesses,^2,3 and much research has focused on the determinants of and barriers to ART adherence and optimal HIV health outcomes. A large body of literature, recently summarized in a set of comprehensive review articles,^4,5 now demonstrates the important role of psychosocial factors, including depression, substance abuse, stress and traumatic life experiences, in influencing ART adherence and treatment outcomes for PLWHA.

Depression, trauma and other types of psychosocial adversity are highly prevalent in PLWHA.⁶ Mood and anxiety disorders, particularly depression, are the most common psychiatric diagnoses,^7–10 and are 5–10 times more common in PLWHA than in the general population.¹¹ In the USA, approximately half of PLWHA have significant depressive symptoms and 20% to 25% meet diagnostic criteria for a depressive disorder.^12,13 Depression is twice as common in PLWHA as in comparable controls.¹⁴ The presence of multiple rather than a single psychiatric diagnosis (e.g. co-morbid depression and substance abuse) is the norm rather than the exception.¹⁵

While depression is widely recognized as an important concern for PLWHA, perhaps less appreciated are the prevalence and consequences of past and ongoing traumatic experiences.¹⁶ Numerous studies have documented substantially higher prevalence of childhood sexual and physical abuse, exposure to other traumatic experiences and subsequent post-traumatic stress disorder (PTSD) among both men and women living with HIV/AIDS compared with nationally representative general population samples (reviewed in Brief et al.¹⁷). This association between trauma history and HIV status may indicate a causal relationship (e.g. childhood sexual abuse has been linked to higher rates of sexual and drug use behaviours that increase the risk of HIV infection) or may reflect the concentration of HIV in marginalized and disadvantaged populations at high risk of trauma exposure.¹⁷

This tapestry of adversity has important implications for patients' success in HIV clinical care. Current mental illness, especially depression and substance abuse, predict lower ART adherence,¹⁸ a greater likelihood of failing ART¹⁹ and increased mortality.²⁰ Similarly, patients with more lifetime trauma exposure are less adherent to ART,²¹ have more emergency room visits and hospitalizations²² and have faster rates of HIV disease progression and mortality.^23,24 These associations have generally shown consistent dose–response relationships: the odds of ART non-adherence²¹ and the incidence of opportunistic infections²⁴ increase with each additional lifetime traumatic experience, and PLWHA with chronic depression over years of follow-up have higher mortality rates than those with intermittent or no depression.²⁰

The evidence linking depression to adverse HIV-related behaviours and outcomes is striking in its strength and consistency.⁵ The studies that have focused on trauma exposure and PTSD in HIV, particularly as they relate to behaviours and health outcomes, are relatively few in number.¹⁷ The definition of the PTSD diagnosis has engendered much debate, especially related to the ‘criterion A problem’ (which types of events should be allowed as potential precipitators of PTSD),²⁵ the ‘threshold problem’ (whether PTSD represents the upper end of a continuous spectrum of psychological response to extreme stress or a clearly bounded pathological state qualitatively distinct from non-pathological stress responses)²⁶ and the veracity of self-report.²⁷ However, a broad consensus supports the existence of the PTSD diagnosis, and a number of psychometrically sound instruments exist to measure both trauma exposure and PTSD symptomatology.^25,28

The pathways through which mental illness and lifetime trauma influence HIV treatment outcomes have not been fully elucidated. Greater severity of depressive symptoms was linked to faster CD4 decline even before the era of highly active ART,²⁹ and some studies have suggested a direct influence of depression on the immune system,³⁰ possibly mediated by diminished natural killer cell counts.^31,32 However, the effect of these psychosocial factors on virological, immunological and clinical outcomes is presumed to operate primarily through reduced ART adherence. Past trauma may influence adherence through current mental health or substance use, trust in the healthcare system, coping styles, social support or self-efficacy, although adjustment for measures of these constructs in observational data has generally not explained the associations between trauma, adherence and outcomes.²¹ Nevertheless, the evidence supporting the relevance of trauma history and mental illness for HIV treatment outcomes is compelling.

Mental health treatment for PLWHA

Effective interventions to address mental health disorders in PLWHA have been well-defined.^33,34 Recent systematic reviews have underscored the efficacy of standard antidepressant and group therapy-based treatment modalities in depressed PLWHA.^35,36 Strategies to address more complicated psychiatric presentations, such as co-morbid mental health and substance abuse disorders, have also shown promising results in reducing psychiatric morbidity.³⁷ Interventions targeted specifically at addressing PTSD in HIV-infected survivors of childhood sexual abuse are also effective in reducing psychiatric symptoms and improving coping skills.^38,39

Further, there is accumulating evidence that treating mental health disorders leads to improved HIV behaviours and clinical outcomes for depressed PLWHA. A small number of randomized clinical trials have shown beneficial effects of various psychotherapy-based interventions for PLWHA on HIV medication adherence and sexual risk behaviours.^39–42 Antidepressant treatment for depressed PLWHA has also been associated with improved HIV medication adherence in retrospective observational data,^43–45 although no experimental data on this question have been published to date.

Challenges for clinical care

Despite the relevance of mental health disorders for HIV outcomes and the availability of proven mental health interventions, the available evidence indicates that mental disorders in PLWHA frequently go undiagnosed and untreated. In a large cohort of patients experiencing HIV care in the USA, nearly half of those meeting criteria for major depression had no record of such a diagnosis in their medical record,⁴⁶ and one-third of those needing mental health services were not receiving them.⁴⁷ These deficiencies in diagnosis and treatment likely reflect a number of dynamics. In wealthier countries, HIV is primarily affecting disadvantaged populations with limited interaction with the healthcare system. For many HIV patients, therefore, their HIV provider effectively serves as their primary care physician, and HIV clinical care is the primary point at which a mental illness could be identified and an intervention could be pursued. Providers trained as infectious diseases specialists, however, may perceive themselves as ill-equipped to look for and treat psychiatric illnesses and therefore may be reluctant to fill such a role. When a mental illness is identified, HIV providers may make a referral to a mental health specialist, yet patients may fail to complete the referral for a variety of reasons, including the stigma of mental health services and financial and time barriers.

How can mental health disorders be addressed more systematically in HIV clinical care? First, to address the under-diagnosis of such disorders, HIV clinics should screen all presenting patients at regular intervals for mental health problems. Several mental health screening instruments have been adapted successfully for such purposes, including instruments that were designed for and validated in HIV patient populations.⁴⁸ Such instruments can usually be rapidly administered and scored by a nurse, assistant or other clinic staff member as part of a standard check-in process. This class of screening instruments generally has relatively high sensitivity but somewhat lower specificity, implying that positive screens require follow-up from a provider with some level of mental health training, such as a licensed social worker, to confirm the presence of a diagnosis.

Once a mental health disorder is identified, mental health treatment options must be in place. While referral to speciality psychiatric services will be required for some patients, the integration of mental health treatment into HIV clinical care settings will likely have the greatest potential for effectively engaging and retaining patients in mental healthcare. While several examples exist of the successful integration of HIV and psychotherapy-based mental healthcare,^37,49,50 the large-scale adaptation of such psychotherapeutic interventions into HIV clinical care remains challenging because of staffing requirements and resource constraints.

Mental health interventions that equip existing HIV clinic staff with the tools to effectively prescribe and monitor antidepressant treatment may be more readily scaled up into widespread practice. One promising approach, known as measurement-based care (MBC),^51,52 is an evidence-based strategy for providing depression treatment in non-psychiatric settings by giving clinical coordinators the tools and supervision needed to accurately identify and effectively manage depression. In the MBC approach, the clinical coordinator provides decision support to the treating non-psychiatric clinician, addressing the lack of psychiatric expertise that is the norm in most HIV treatment settings without requiring the on-site presence of a psychiatrist. These clinical coordinators perform initial assessments, monitor symptoms and side effects using standardized tools at regular intervals and make dosing recommendations to the treating physician based on best-practices guidelines. The clinical coordinator role can be effectively filled by a social worker or nurse given appropriate training and supervision,⁵³ giving this model the potential to be replicated in a wide range of resource-constrained HIV treatment settings. MBC has been shown to be effective in treating depression in primary care settings⁵⁴ and has been successfully adapted to resource-constrained environments,⁵³ although it has not previously been tested in HIV patients. Such approaches parallel the recent efforts in chronic disease models such as cardiovascular disease and diabetes care to empower ‘care managers’ to safely and effectively implement much of the day-to-day disease management with appropriate oversight from specialty medical providers.

Future directions

Research has demonstrated the high prevalence of mental health disorders as well as traumatic and severely stressful experiences in the lives of PLWHA. Individuals with mental illness, particularly depression and histories of traumatic experiences, are at increased risk of poor HIV medication adherence, HIV treatment failure and adverse clinical outcomes. While the need for comprehensive, accessible and effective mental health services for PLWHA is clear, the challenges are equally evident. At least three areas suggest themselves as high priorities for future research. First, mental health interventions should be developed and evaluated that are affordable, cost-effective and feasible for widespread integration into HIV clinical care. Second, evidence should be gathered on the effectiveness of such interventions not only in improving mental health but also in impacting HIV medication adherence and clinical outcomes so as to guide policy decisions on the appropriate allocation of limited resources. Third, particular attention is warranted for interventions to identify individuals in HIV clinical settings with histories of traumatic experiences and to understand and address the mechanisms through which such histories pose barriers to effective HIV treatment. In this era of highly effective long-term HIV treatment, addressing the mental health burdens of PLWHA will be an essential component of strategies to achieve optimal treatment response and health outcomes in HIV clinical care.

Funding

Not applicable. B. W. P. currently receives salary support from the National Institute of Mental Health and the National Institute of Nursing Research of the National Institutes of Health.

Transparency declarations

In the past 5 years, B. W. P. has received an honorarium from the British HIV Association and has received salary support from the GlaxoSmithKline North Carolina Foundation.

Acknowledgements

I appreciate the critical input of Drs Michael Mugavero, Rae Jean Proescholdbell, Susan Reif and Kathryn Whetten into drafts of this article.

References

1. The Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293–9. [PMC free article] [PubMed]

2. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133:21–30. [PubMed]

3. Bangsberg DR. Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression. Clin Infect Dis. 2006;43:939–41. [PubMed]

4. Leserman J, Temoshok LR. A road well traveled (although not yet a super highway) Psychosom Med. 2008;70:521–2. [PubMed]

5. Leserman J. Role of depression, stress, and trauma in HIV disease progression. Psychosom Med. 2008;70:539–45. [PubMed]

6. Whetten K, Reif S, Whetten R, et al. Trauma, mental health, distrust, and stigma among HIV-positive persons: implications for effective care. Psychosom Med. 2008;70:531–8. [PubMed]

7. Kelly B, Raphael B, Judd F, et al. Psychiatric disorder in HIV infection. Aust N Z J Psychiatry. 1998;32:441–53. [PubMed]

8. Kilbourne AM, Justice AC, Rabeneck L, et al. General medical and psychiatric comorbidity among HIV-infected veterans in the post-HAART era. J Clin Epidemiol. 2001;54(Suppl 1):S22–8. [PubMed]

9. Lyketsos CG, Hanson A, Fishman M, et al. Screening for psychiatric morbidity in a medical outpatient clinic for HIV infection: the need for a psychiatric presence. Int J Psychiatry Med. 1994;24:103–13. [PubMed]

10. Pence BW, Miller WC, Whetten K, et al. Prevalence of DSM-IV-defined mood, anxiety, and substance use disorders in an HIV clinic in the Southeastern United States. J Acquir Immune Defic Syndr. 2006;42:298–306. [PubMed]

11. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8–19. [PubMed]

12. Bing EG, Burnam MA, Longshore D, et al. Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Arch Gen Psychiatry. 2001;58:721–8. [PubMed]

13. Orlando M, Burnam MA, Beckman R, et al. Re-estimating the prevalence of psychiatric disorders in a nationally representative sample of persons receiving care for HIV: results from the HIV Cost and Services Utilization Study. Int J Methods Psychiatr Res. 2002;11:75–82. [PubMed]

14. Ciesla JA, Roberts JE. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry. 2001;158:725–30. [PubMed]

15. Gaynes BN, Pence BW, Eron JJ, Jr, et al. Prevalence and comorbidity of psychiatric diagnoses based on reference standard in an HIV+ patient population. Psychosom Med. 2008;70:505–11. [PMC free article] [PubMed]

16. Whetten-Goldstein K, Nguyen TQ. ‘You're the first one I've told’: New faces of HIV in the South. New Brunswick, NJ: Rutgers University Press; 2002.

17. Brief DJ, Bollinger AR, Vielhauer MJ, et al. Understanding the interface of HIV, trauma, post-traumatic stress disorder, and substance use and its implications for health outcomes. AIDS Care. 2004;16(Suppl 1):S97–120. [PubMed]

18. Gordillo V, del Amo J, Soriano V, et al. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS. 1999;13:1763–9. [PubMed]

19. Pence BW, Miller WC, Gaynes BN, et al. Psychiatric illness and virologic response in patients initiating highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2007;44:159–66. [PubMed]

20. Ickovics JR, Hamburger ME, Vlahov D, et al. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA. 2001;285:1466–74. [PubMed]

21. Mugavero M, Ostermann J, Whetten K, et al. Barriers to antiretroviral adherence: the importance of depression, abuse, and other traumatic events. AIDS Patient Care STDS. 2006;20:418–28. [PubMed]

22. Leserman J, Whetten K, Lowe K, et al. How trauma, recent stressful events, and PTSD affect functional health status and health utilization in HIV-infected patients in the south. Psychosom Med. 2005;67:500–7. [PubMed]

23. Leserman J, Pence BW, Whetten K, et al. Relation of lifetime trauma and depressive symptoms to mortality in HIV. Am J Psychiatry. 2007;164:1707–13. [PubMed]

24. Mugavero MJ, Pence BW, Whetten K, et al. Predictors of AIDS-related morbidity and mortality in a southern U.S. cohort. AIDS Patient Care STDS. 2007;21:681–90. [PubMed]

25. Weathers FW, Keane TM. The criterion A problem revisited: controversies and challenges in defining and measuring psychological trauma. J Trauma Stress. 2007;20:107–21. [PubMed]

26. Ruscio AM, Ruscio J, Keane TM. The latent structure of posttraumatic stress disorder: a taxometric investigation of reactions to extreme stress. J Abnorm Psychol. 2002;111:290–301. [PubMed]

27. Fairbank JA, McCaffrey RJ, Keane TM. Psychometric detection of fabricated symptoms of posttraumatic stress disorder. Am J Psychiatry. 1985;142:501–3. [PubMed]

28. Keane TM, Marshall AD, Taft CT. Posttraumatic stress disorder: etiology, epidemiology, and treatment outcome. Annu Rev Clin Psychol. 2006;2:161–97. [PubMed]

29. Burack JH, Barrett DC, Stall RD, et al. Depressive symptoms and CD4 lymphocyte decline among HIV-infected men. JAMA. 1993;270:2568–73. [PubMed]

30. Herbert TB, Cohen S. Depression and immunity: a meta-analytic review. Psychol Bull. 1993;113:472–86. [PubMed]

31. Greeson JM, Hurwitz BE, Llabre MM, et al. Psychological distress, killer lymphocytes and disease severity in HIV/AIDS. Brain Behav Immun. 2008;22:901–11. [PubMed]

32. Evans DL, Lynch KG, Benton T, et al. Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome. Biol Psychiatry. 2008;63:899–905. [PMC free article] [PubMed]

33. Angelino AF, Treisman GJ. Management of psychiatric disorders in patients infected with human immunodeficiency virus. Clin Infect Dis. 2001;33:847–56. [PubMed]

34. Treisman G, Angelino AF. The Psychiatry of AIDS: A Guide to Diagnosis and Treatment. Baltimore, MD: The Johns Hopkins University Press; 2004.

35. Himelhoch S, Medoff DR. Efficacy of antidepressant medication among HIV-positive individuals with depression: a systematic review and meta-analysis. AIDS Patient Care STDS. 2005;19:813–22. [PubMed]

36. Himelhoch S, Medoff DR, Oyeniyi G. Efficacy of group psychotherapy to reduce depressive symptoms among HIV-infected individuals: a systematic review and meta-analysis. AIDS Patient Care STDS. 2007;21:732–9. [PubMed]

37. Whetten K, Reif S, Ostermann J, et al. Improving health outcomes among individuals with HIV, mental illness, and substance use disorders in the Southeast. AIDS Care. 2006;18(Suppl 1):S18–26. [PubMed]

38. Sikkema KJ, Hansen NB, Kochman A, et al. Outcomes from a group intervention for coping with HIV/AIDS and childhood sexual abuse: reductions in traumatic stress. AIDS Behav. 2007;11:49–60. [PubMed]

39. Wyatt GE, Longshore D, Chin D, et al. The efficacy of an integrated risk reduction intervention for HIV-positive women with child sexual abuse histories. AIDS Behav. 2004;8:453–62. [PubMed]

40. Weber R, Christen L, Christen S, et al. Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antivir Ther. 2004;9:85–95. [PubMed]

41. Safren S, Kraus RO, O'Cleirigh C, et al. CBT for HIV medication adherence and depression: process and outcomes at post-treatment and three-month cross over. Ann Behav Med. 2006;31:S006.

42. Sikkema KJ, Wilson PA, Hansen NB, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr. 2008;47:506–13. [PubMed]

43. Yun LW, Maravi M, Kobayashi JS, et al. Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients. J Acquir Immune Defic Syndr. 2005;38:432–8. [PubMed]

44. Walkup J, Wei W, Sambamoorthi U, et al. Antidepressant treatment and adherence to combination antiretroviral therapy among patients with AIDS and diagnosed depression. Psychiatr Q. 2008;79:43–53. [PMC free article] [PubMed]

45. Horberg MA, Silverberg MJ, Hurley LB, et al. Effects of depression and selective serotonin reuptake inhibitor use on adherence to highly active antiretroviral therapy and on clinical outcomes in HIV-infected patients. J Acquir Immune Defic Syndr. 2008;47:384–90. [PubMed]

46. Asch SM, Kilbourne AM, Gifford AL, et al. Underdiagnosis of depression in HIV: who are we missing? J Gen Intern Med. 2003;18:450–60. [PMC free article] [PubMed]

47. Taylor SL, Burnam MA, Sherbourne C, et al. The relationship between type of mental health provider and met and unmet mental health needs in a nationally representative sample of HIV-positive patients. J Behav Health Serv Res. 2004;31:149–63. [PubMed]

48. Pence BW, Gaynes BN, Whetten K, et al. Validation of a brief screening instrument for substance abuse and mental illness in HIV-positive patients. J Acquir Immune Defic Syndr. 2005;40:434–44. [PubMed]

49. Sorensen JL, Dilley J, London J, et al. Case management for substance abusers with HIV/AIDS: a randomized clinical trial. Am J Drug Alcohol Abuse. 2003;29:133–50. [PubMed]

50. Andersen M, Paliwoda J, Kaczynski R, et al. Integrating medical and substance abuse treatment for addicts living with HIV/AIDS: evidence-based nursing practice model. Am J Drug Alcohol Abuse. 2003;29:847–59. [PubMed]

51. Gaynes BN, Rush AJ, Trivedi MH, et al. Primary versus specialty care outcomes for depressed outpatients managed with measurement-based care: results from STAR*D. J Gen Intern Med. 2008;23:551–60. [PMC free article] [PubMed]

52. Trivedi MH, Rush AJ, Gaynes BN, et al. Maximizing the adequacy of medication treatment in controlled trials and clinical practice: STAR*D measurement-based care. Neuropsychopharmacology. 2007;32:2479–89. [PubMed]

53. Landis SE, Gaynes BN, Morrissey JP, et al. Generalist care managers for the treatment of depressed medicaid patients in North Carolina: a pilot study. BMC Fam Pract. 2007;8:7. [PMC free article] [PubMed]

54. Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007;164:201–4. [PubMed]

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