UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Palliative care: Issues in HIV/AIDS in adults

Authors
Jessica Merlin, MD
Meera Pahuja, MD
Peter A Selwyn, MD, MPH
Section Editor
R Sean Morrison, MD
Deputy Editors
Diane MF Savarese, MD
Allyson Bloom, MD

INTRODUCTION

Palliative care is an interdisciplinary medical specialty that focuses on preventing and relieving suffering and on supporting the best possible quality of life for patients facing serious illness and their families. The primary tenets are symptom management; establishing goals of care that are in keeping with the patient’s values and preferences; consistent and sustained communication between the patient and caregivers; and psychosocial, spiritual, and practical support, both to patients and their caregivers. For patients with a variety of advanced illnesses, palliative care is applicable early in the course of the disease in conjunction with disease-modifying therapies (the simultaneous care model); it is not limited to end of life care [1]. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)

In the early days of the human immunodeficiency virus (HIV) epidemic, all care for individuals with HIV-related disease was, by definition, palliative. With the introduction of tolerable, effective antiretroviral therapy (ART), HIV infection was transformed from a terminal disease with a uniformly poor prognosis to a serious chronic illness, at least in resource-rich settings among individuals who know their HIV status and are adherent to ART [2]. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "The natural history and clinical features of HIV infection in adults and adolescents".)

However, even in the modern treatment era, individuals with HIV fit well within the “serious illness” paradigm for which early integration of palliative care plays a complementary role to active treatment of the underlying disease. These patients have a substantial burden of medical and psychiatric comorbidities, pain, and other symptoms throughout the course of the disease, and a wide-ranging need for psychosocial, family, and care-planning support. Although no studies have investigated this to date, it is possible that treatment of these comorbidities could improve HIV outcomes, such as adherence to ART, retention in HIV primary care, and virologic suppression.

This topic review describes an approach to palliative care in patients with HIV/acquired immunodeficiency syndrome (AIDS) in resource-rich settings that is based on the available literature and our clinical experience. The specific areas in which palliative care principles and expertise might assist in the care of individuals with HIV infection include establishing goals of care, advance care planning, making decisions about continuing or discontinuing ART as the end of life approaches, and symptom management.

OVERVIEW OF HIV STAGES AND TREATMENT

HIV infection can be divided into the following stages:

                          

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: May 2017. | This topic last updated: Jun 01, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. World Heealth Organization. Guidelines for palliative care. http://www.who.int/entity/cancer/palliative/definition/en (Accessed on August 22, 2016).
  2. Aberg JA, Kaplan JE, Libman H, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2009; 49:651.
  3. UNAIDS. Global AIDS update, 2016. http://www.unaids.org/sites/default/files/media_asset/global-AIDS-update-2016_en.pdf.
  4. Harrison KM, Song R, Zhang X. Life expectancy after HIV diagnosis based on national HIV surveillance data from 25 states, United States. J Acquir Immune Defic Syndr 2010; 53:124.
  5. May MT, Gompels M, Delpech V, et al. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS 2014; 28:1193.
  6. Cowell A, Shenoi SV, Kyriakides TC, et al. Trends in hospital deaths among human immunodeficiency virus-infected patients during the antiretroviral therapy era, 1995 to 2011. J Hosp Med 2015; 10:608.
  7. Bhaskaran K, Hamouda O, Sannes M, et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 2008; 300:51.
  8. Rodger AJ, Lodwick R, Schechter M, et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 2013; 27:973.
  9. Djawe K, Buchacz K, Hsu L, et al. Mortality Risk After AIDS-Defining Opportunistic Illness Among HIV-Infected Persons--San Francisco, 1981-2012. J Infect Dis 2015; 212:1366.
  10. Schwarcz L, Chen MJ, Vittinghoff E, et al. Declining incidence of AIDS-defining opportunistic illnesses: results from 16 years of population-based AIDS surveillance. AIDS 2013; 27:597.
  11. Lima VD, Lourenço L, Yip B, et al. AIDS incidence and AIDS-related mortality in British Columbia, Canada, between 1981 and 2013: a retrospective study. Lancet HIV 2015; 2:e92.
  12. Smit M, Brinkman K, Geerlings S, et al. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis 2015; 15:810.
  13. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011; 53:1120.
  14. Centers for Disease Control and Prevention (CDC). Vital signs: HIV testing and diagnosis among adults--United States, 2001-2009. MMWR Morb Mortal Wkly Rep 2010; 59:1550.
  15. Mocroft A, Lundgren JD, Sabin ML, et al. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE). PLoS Med 2013; 10:e1001510.
  16. Langebeek N, Gisolf EH, Reiss P, et al. Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis. BMC Med 2014; 12:142.
  17. Rebeiro P, Althoff KN, Buchacz K, et al. Retention among North American HIV-infected persons in clinical care, 2000-2008. J Acquir Immune Defic Syndr 2013; 62:356.
  18. Fleishman JA, Yehia BR, Moore RD, et al. Establishment, retention, and loss to follow-up in outpatient HIV care. J Acquir Immune Defic Syndr 2012; 60:249.
  19. Mugavero MJ, Lin HY, Willig JH, et al. Missed visits and mortality among patients establishing initial outpatient HIV treatment. Clin Infect Dis 2009; 48:248.
  20. Antiretroviral Therapy Cohort Collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis 2010; 50:1387.
  21. Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384:241.
  22. Shen JM, Blank A, Selwyn PA. Predictors of mortality for patients with advanced disease in an HIV palliative care program. J Acquir Immune Defic Syndr 2005; 40:445.
  23. Gopal S, Patel MR, Yanik EL, et al. Temporal trends in presentation and survival for HIV-associated lymphoma in the antiretroviral therapy era. J Natl Cancer Inst 2013; 105:1221.
  24. Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. AIDS 2014; 28:453.
  25. Valderas JM, Starfield B, Sibbald B, et al. Defining comorbidity: implications for understanding health and health services. Ann Fam Med 2009; 7:357.
  26. Le Reste JY, Nabbe P, Rivet C, et al. The European general practice research network presents the translations of its comprehensive definition of multimorbidity in family medicine in ten European languages. PLoS One 2015; 10:e0115796.
  27. Hasse B, Ledergerber B, Furrer H, et al. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis 2011; 53:1130.
  28. Desquilbet L, Jacobson LP, Fried LP, et al. A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men. J Gerontol A Biol Sci Med Sci 2011; 66:1030.
  29. Önen NF, Overton ET. A review of premature frailty in HIV-infected persons; another manifestation of HIV-related accelerated aging. Curr Aging Sci 2011; 4:33.
  30. Joshi D, O'Grady J, Dieterich D, et al. Increasing burden of liver disease in patients with HIV infection. Lancet 2011; 377:1198.
  31. Rodriguez-Penney AT, Iudicello JE, Riggs PK, et al. Co-morbidities in persons infected with HIV: increased burden with older age and negative effects on health-related quality of life. AIDS Patient Care STDS 2013; 27:5.
  32. Glass TR, Ungsedhapand C, Wolbers M, et al. Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study. HIV Med 2006; 7:404.
  33. Izzedine H, Hulot JS, Vittecoq D, et al. Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study. Nephrol Dial Transplant 2005; 20:743.
  34. Operskalski EA, Kovacs A. HIV/HCV co-infection: pathogenesis, clinical complications, treatment, and new therapeutic technologies. Curr HIV/AIDS Rep 2011; 8:12.
  35. Bedimo RJ, McGinnis KA, Dunlap M, et al. Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression. J Acquir Immune Defic Syndr 2009; 52:203.
  36. Walker Harris V, Brown TT. Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. J Infect Dis 2012; 205 Suppl 3:S391.
  37. Galvan FH, Burnam MA, Bing EG. Co-occurring psychiatric symptoms and drug dependence or heavy drinking among HIV-positive people. J Psychoactive Drugs 2003; 35 Suppl 1:153.
  38. 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.
  39. Gaynes BN, Pence BW, Eron JJ Jr, Miller WC. Prevalence and comorbidity of psychiatric diagnoses based on reference standard in an HIV+ patient population. Psychosom Med 2008; 70:505.
  40. Halman M, Carusone SC, Stranks S, et al. Complex care needs of patients with late-stage HIV disease: a retrospective study. AIDS Care 2014; 26:320.
  41. Tegger MK, Crane HM, Tapia KA, et al. The effect of mental illness, substance use, and treatment for depression on the initiation of highly active antiretroviral therapy among HIV-infected individuals. AIDS Patient Care STDS 2008; 22:233.
  42. Gonzalez JS, Batchelder AW, Psaros C, Safren SA. Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr 2011; 58:181.
  43. Mellins CA, Havens JF, McDonnell C, et al. Adherence to antiretroviral medications and medical care in HIV-infected adults diagnosed with mental and substance abuse disorders. AIDS Care 2009; 21:168.
  44. Dalessandro M, Conti CM, Gambi F, et al. Antidepressant therapy can improve adherence to antiretroviral regimens among HIV-infected and depressed patients. J Clin Psychopharmacol 2007; 27:58.
  45. Power R, Koopman C, Volk J, et al. Social support, substance use, and denial in relationship to antiretroviral treatment adherence among HIV-infected persons. AIDS Patient Care STDS 2003; 17:245.
  46. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 2007; 46:32.
  47. Justice AC, Holmes W, Gifford AL, et al. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol 2001; 54 Suppl 1:S77.
  48. Justice AC, McGinnis KA, Skanderson M, et al. Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers. HIV Med 2010; 11:143.
  49. Justice AC, Modur SP, Tate JP, et al. Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: a North American cross cohort analysis. J Acquir Immune Defic Syndr 2013; 62:149.
  50. Taskforce. Saacmg.. Medical Guidelines for Determining Prognosis in Selected Non-cancer Disease, 2nd ed, The National Hospice Organization, Arlington, VA 1996.
  51. Merlins JS, Tucker RO, Saag MS, Selwyn PA. The role of palliative care in the current HIV treatment era in developed countries. Top Antivir Med 2013; 21:20.
  52. Selwyn PA, Forstein M. Overcoming the false dichotomy of curative vs palliative care for late-stage HIV/AIDS: "let me live the way I want to live, until I can't". JAMA 2003; 290:806.
  53. World Health Organization policy on Palliative care in HIV/AIDS http://www.who.int/hiv/topics/palliative/PalliativeCare/en/.
  54. Joint United Nations progam on HIV/AIDS (UNAIDS). AIDS palliative care: a techinical update. Geneva:UNAIDS; 2000. http://data.unaids.org/Publications/IRC-pub05/JC453-PalliCare-TU_en.pdf (Accessed on February 02, 2017).
  55. Rhodes RL, Nazir F, Lopez S, et al. Use and Predictors of End-of-Life Care Among HIV Patients in a Safety Net Health System. J Pain Symptom Manage 2016; 51:120.
  56. Perry BA, Westfall AO, Molony E, et al. Characteristics of an ambulatory palliative care clinic for HIV-infected patients. J Palliat Med 2013; 16:934.
  57. Johnson A, Condon KD, Mapas-Dimaya AC, et al. Report of an HIV clinic-based pain management program and utilization of health status and health service by HIV patients. J Opioid Manag 2012; 8:17.
  58. Lofgren S, Friedman R, Ghermay R, et al. Integrating early palliative care for patients with HIV: provider and patient perceptions of symptoms and need for services. Am J Hosp Palliat Care 2015; 32:829.
  59. Ruiz M, Cefalu C. Palliative care program for human immunodeficiency virus-infected patients: rebuilding of an academic urban program. Am J Hosp Palliat Care 2011; 28:16.
  60. Green K, Tuan T, Hoang TV, et al. Integrating palliative care into HIV outpatient clinical settings: preliminary findings from an intervention study in Vietnam. J Pain Symptom Manage 2010; 40:31.
  61. Wube M, Horne CJ, Stuer F. Building a palliative care program in Ethiopia: the impact on HIV and AIDS patients and their families. J Pain Symptom Manage 2010; 40:6.
  62. Harding R, Simms V, Alexander C, et al. Can palliative care integrated within HIV outpatient settings improve pain and symptom control in a low-income country? A prospective, longitudinal, controlled intervention evaluation. AIDS Care 2013; 25:795.
  63. Harding R, Karus D, Easterbrook P, et al. Does palliative care improve outcomes for patients with HIV/AIDS? A systematic review of the evidence. Sex Transm Infect 2005; 81:5.
  64. Nickel JT, Salsberry PJ, Caswell RJ, et al. Quality of life in nurse case management of persons with AIDS receiving home care. Res Nurs Health 1996; 19:91.
  65. Hardon AP, Akurut D, Comoro C, et al. Hunger, waiting time and transport costs: time to confront challenges to ART adherence in Africa. AIDS Care 2007; 19:658.
  66. Ammassari A, Murri R, Pezzotti P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr 2001; 28:445.
  67. Roura M, Busza J, Wringe A, et al. Barriers to sustaining antiretroviral treatment in Kisesa, Tanzania: a follow-up study to understand attrition from the antiretroviral program. AIDS Patient Care STDS 2009; 23:203.
  68. Quill TE, Abernethy AP. Generalist plus specialist palliative care--creating a more sustainable model. N Engl J Med 2013; 368:1173.
  69. Merlin JS, Cen L, Praestgaard A, et al. Pain and physical and psychological symptoms in ambulatory HIV patients in the current treatment era. J Pain Symptom Manage 2012; 43:638.
  70. Lee KA, Gay C, Portillo CJ, et al. Symptom experience in HIV-infected adults: a function of demographic and clinical characteristics. J Pain Symptom Manage 2009; 38:882.
  71. Jaggers JR, Dudgeon WD, Burgess S, et al. Psychological correlates of HIV-related symptom distress. J Assoc Nurses AIDS Care 2014; 25:309.
  72. Lampe FC, Harding R, Smith CJ, et al. Physical and psychological symptoms and risk of virologic rebound among patients with virologic suppression on antiretroviral therapy. J Acquir Immune Defic Syndr 2010; 54:500.
  73. Gay C, Portillo CJ, Kelly R, et al. Self-reported medication adherence and symptom experience in adults with HIV. J Assoc Nurses AIDS Care 2011; 22:257.
  74. Cooper V, Gellaitry G, Hankins M, et al. The influence of symptom experiences and attributions on adherence to highly active anti-retroviral therapy (HAART): a six-month prospective, follow-up study. AIDS Care 2009; 21:520.
  75. Billings JA, Bernacki R. Strategic targeting of advance care planning interventions: the Goldilocks phenomenon. JAMA Intern Med 2014; 174:620.
  76. Kimmel AL, Wang J, Scott RK, et al. FAmily CEntered (FACE) advance care planning: Study design and methods for a patient-centered communication and decision-making intervention for patients with HIV/AIDS and their surrogate decision-makers. Contemp Clin Trials 2015; 43:172.
  77. Mouton C, Teno JM, Mor V, Piette J. Communication of preferences for care among human immunodeficiency virus-infected patients. Barriers to informed decisions? Arch Fam Med 1997; 6:342.
  78. Wenger NS, Kanouse DE, Collins RL, et al. End-of-life discussions and preferences among persons with HIV. JAMA 2001; 285:2880.
  79. Erlandson KM, Allshouse AA, Duong S, et al. HIV, aging, and advance care planning: are we successfully planning for the future? J Palliat Med 2012; 15:1124.
  80. Ho VW, Thiel EC, Rubin HR, Singer PA. The effect of advance care planning on completion of advance directives and patient satisfaction in people with HIV/AIDS. AIDS Care 2000; 12:97.
  81. Hirschman KB, Abbott KM, Hanlon AL, et al. What factors are associated with having an advance directive among older adults who are new to long term care services? J Am Med Dir Assoc 2012; 13:82.e7.
  82. Alano GJ, Pekmezaris R, Tai JY, et al. Factors influencing older adults to complete advance directives. Palliat Support Care 2010; 8:267.
  83. Dobalian A. Advance care planning documents in nursing facilities: results from a nationally representative survey. Arch Gerontol Geriatr 2006; 43:193.
  84. Sangarlangkarn A, Merlin JS, Tucker RO, Kelley AS. Advance Care Planning and HIV Infection in the Era of Antiretroviral Therapy: A Review. Top Antivir Med 2016; 23:174.
  85. Mosack KE, Wandrey RL. Discordance in HIV-positive patient and health care provider perspectives on death, dying, and end-of-life care. Am J Hosp Palliat Care 2015; 32:161.
  86. Pecanac KE, Repenshek MF, Tennenbaum D, Hammes BJ. Respecting Choices® and advance directives in a diverse community. J Palliat Med 2014; 17:282.
  87. Respecting choices http://www.gundersenhealth.org/respecting-choices/about-us/stages-of-planning (Accessed on December 07, 2015).
  88. Fast Facts and cooncepts #102. Highly active antiretroviral therapy and hospice. Palliative Care Network of Wisconsin, June 2015 http://www.mypcnow.org/blank-ip7pk (Accessed on January 30, 2017).
  89. Simpson DM, Haidich AB, Schifitto G, et al. Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels. AIDS 2002; 16:407.
  90. McArthur JC, McClernon DR, Cronin MF, et al. Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann Neurol 1997; 42:689.
  91. Frenkel LM, Mullins JI. Should patients with drug-resistant HIV-1 continue to receive antiretroviral therapy? N Engl J Med 2001; 344:520.
  92. Gudin J. Opioid therapies and cytochrome p450 interactions. J Pain Symptom Manage 2012; 44:S4.
  93. Merskey H, Bogduk, N. Part III: Pain terms, a current list with definitions and notes on usage. In: Classification of Chronic Pain, 2nd ed, IASP Task Force on Taxonomy, Merskey H, Bogduk, N (Eds), IASP Press, 1994.
  94. Merlin JS, Walcott MM, Herbey I, et al. Qualitative investigation of a Brief Chronic Pain Screening tool in HIV-infected patients. AIDS Patient Care STDS 2014; 28:176.
  95. Merlin JS, Westfall AO, Raper JL, et al. Pain, mood, and substance abuse in HIV: implications for clinic visit utilization, antiretroviral therapy adherence, and virologic failure. J Acquir Immune Defic Syndr 2012; 61:164.
  96. Miaskowski C, Penko JM, Guzman D, et al. Occurrence and characteristics of chronic pain in a community-based cohort of indigent adults living with HIV infection. J Pain 2011; 12:1004.
  97. Cervia LD, McGowan JP, Weseley AJ. Clinical and demographic variables related to pain in HIV-infected individuals treated with effective, combination antiretroviral therapy (cART). Pain Med 2010; 11:498.
  98. Silverberg MJ, Gore ME, French AL, et al. Prevalence of clinical symptoms associated with highly active antiretroviral therapy in the Women's Interagency HIV Study. Clin Infect Dis 2004; 39:717.
  99. Uebelacker LA, Weisberg RB, Herman DS, et al. Chronic Pain in HIV-Infected Patients: Relationship to Depression, Substance Use, and Mental Health and Pain Treatment. Pain Med 2015; 16:1870.
  100. Aouizerat BE, Miaskowski CA, Gay C, et al. Risk factors and symptoms associated with pain in HIV-infected adults. J Assoc Nurses AIDS Care 2010; 21:125.
  101. Epidemiology of chronic pain in HIV-infected individuals.. In: Chronic Pand and HIV: A Practical Approach, Merlin JS, Selwyn PA, Treisman GJ, Giovanniello AG (Eds), Wiley-Blackwell, 2016.
  102. Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research, The National Academies Press, Washington, DC 2011.
  103. Ruiz M, Armstrong M, Ogboukiri T, Anwar D. Patterns of pain medication use during last months of life in HIV-infected populations: the experience of an academic outpatient clinic. Am J Hosp Palliat Care 2014; 31:793.
  104. Merlin JS, Walcott M, Ritchie C, et al. 'Two pains together': patient perspectives on psychological aspects of chronic pain while living with HIV. PLoS One 2014; 9:e111765.
  105. Tsao JC, Soto T. Pain in persons living with HIV and comorbid psychologic and substance use disorders. Clin J Pain 2009; 25:307.
  106. Malvar J, Vaida F, Sanders CF, et al. Predictors of new-onset distal neuropathic pain in HIV-infected individuals in the era of combination antiretroviral therapy. Pain 2015; 156:731.
  107. Berg KM, Cooperman NA, Newville H, Arnsten JH. Self-efficacy and depression as mediators of the relationship between pain and antiretroviral adherence. AIDS Care 2009; 21:244.
  108. Merlin JS, Westfall AO, Chamot E, et al. Pain is independently associated with impaired physical function in HIV-infected patients. Pain Med 2013; 14:1985.
  109. Tsui JI, Cheng DM, Quinn E, et al. Pain and Mortality Risk in a Cohort of HIV-Infected Persons with Alcohol Use Disorders. AIDS Behav 2016; 20:583.
  110. Merlin JS, Westfall AO, Chamot E, et al. Quantitative Evaluation of an Instrument to Identify Chronic Pain in HIV-Infected Individuals. AIDS Res Hum Retroviruses 2015; 31:623.
  111. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994; 23:129.
  112. Krebs EE, Lorenz KA, Bair MJ, et al. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med 2009; 24:733.
  113. Molony E, Westfall AO, Perry BA, et al. Low back pain and associated imaging findings among HIV-infected patients referred to an HIV/palliative care clinic. Pain Med 2014; 15:418.
  114. Turk DC, Dworkin RH, Allen RR, et al. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain 2003; 106:337.
  115. Merlin JS, Bulls HW, Vucovich LA, et al. Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review. AIDS Care 2016; 28:1506.
  116. Hahn K, Arendt G, Braun JS, et al. A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies. J Neurol 2004; 251:1260.
  117. Simpson DM, Schifitto G, Clifford DB, et al. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology 2010; 74:413.
  118. Simpson DM, Brown S, Tobias J, NGX-4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008; 70:2305.
  119. Clifford DB, Simpson DM, Brown S, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr 2012; 59:126.
  120. Blinderman CD, Sekine R, Zhang B, et al. Methadone as an analgesic for patients with chronic pain in methadone maintenance treatment programs (MMTPs). J Opioid Manag 2009; 5:107.
  121. Newshan G, Lefkowitz M. Transdermal fentanyl for chronic pain in AIDS: a pilot study. J Pain Symptom Manage 2001; 21:69.
  122. Koeppe J, Lyda K, Johnson S, Armon C. Variables associated with decreasing pain among persons living with human immunodeficiency virus: a longitudinal follow-up study. Clin J Pain 2012; 28:32.
  123. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015; 162:276.
  124. Hansen L, Penko J, Guzman D, et al. Aberrant behaviors with prescription opioids and problem drug use history in a community-based cohort of HIV-infected individuals. J Pain Symptom Manage 2011; 42:893.
  125. Knowlton AR, Nguyen TQ, Robinson AC, et al. Pain Symptoms Associated with Opioid Use among Vulnerable Persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention. J Palliat Care 2015; 31:228.
  126. Merlin JS, Walcott M, Kerns R, et al. Pain self-management in HIV-infected individuals with chronic pain: a qualitative study. Pain Med 2015; 16:706.
  127. Weisberg DF, Gordon KS, Barry DT, et al. Long-term Prescription of Opioids and/or Benzodiazepines and Mortality Among HIV-Infected and Uninfected Patients. J Acquir Immune Defic Syndr 2015; 69:223.
  128. Koeppe J, Armon C, Lyda K, et al. Ongoing pain despite aggressive opioid pain management among persons with HIV. Clin J Pain 2010; 26:190.
  129. Koeppe J, Lyda K, Armon C. Association between opioid use and health care utilization as measured by emergency room visits and hospitalizations among persons living with HIV. Clin J Pain 2013; 29:957.
  130. Lum PJ, Little S, Botsko M, et al. Opioid-prescribing practices and provider confidence recognizing opioid analgesic abuse in HIV primary care settings. J Acquir Immune Defic Syndr 2011; 56 Suppl 1:S91.
  131. Starrels JL, Peyser D, Fox AD, et al. HIV treatment providers' perspectives on opioid prescribing for chronic pain: The overriding concern to retain patients in care [oral abstract presentation]. Paper presented at: Association of Medical Education and Research in Substance Abuse, Bethesda MD, November 8, 2013.
  132. Gaither JR, Goulet JL, Becker WC, et al. Guideline-concordant management of opioid therapy among human immunodeficiency virus (HIV)-infected and uninfected veterans. J Pain 2014; 15:1130.
  133. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med 2005; 6:432.
  134. Nuckols TK, Anderson L, Popescu I, et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med 2014; 160:38.
  135. McGowan J, Sherr L, Rodger A, et al. Effects of age on symptom burden, mental health and quality of life amongst people with HIV in the UK. J Int AIDS Soc 2014; 17:19511.
  136. Edelman EJ, Gordon K, Justice AC. Patient and provider-reported symptoms in the post-cART era. AIDS Behav 2011; 15:853.
  137. Barroso J, Leserman J, Harmon JL, et al. Fatigue in HIV-Infected People: A Three-Year Observational Study. J Pain Symptom Manage 2015; 50:69.
  138. Pence BW, Barroso J, Harmon JL, et al. Chronicity and remission of fatigue in patients with established HIV infection. AIDS Patient Care STDS 2009; 23:239.
  139. Jong E, Oudhoff LA, Epskamp C, et al. Predictors and treatment strategies of HIV-related fatigue in the combined antiretroviral therapy era. AIDS 2010; 24:1387.
  140. Barroso J, Hammill BG, Leserman J, et al. Physiological and psychosocial factors that predict HIV-related fatigue. AIDS Behav 2010; 14:1415.
  141. Payne BA, Hateley CL, Ong EL, et al. HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms? HIV Med 2013; 14:247.
  142. Leserman J, Barroso J, Pence BW, et al. Trauma, stressful life events and depression predict HIV-related fatigue. AIDS Care 2008; 20:1258.
  143. Barroso J, Harmon JL, Madison JL, Pence BW. Intensity, chronicity, circumstances, and consequences of HIV-related fatigue: a longitudinal study. Clin Nurs Res 2014; 23:514.
  144. Al-Dakkak I, Patel S, McCann E, et al. The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: a systematic review and meta-analysis. AIDS Care 2013; 25:400.
  145. Pence BW, Barroso J, Leserman J, et al. Measuring fatigue in people living with HIV/AIDS: psychometric characteristics of the HIV-related fatigue scale. AIDS Care 2008; 20:829.
  146. Mücke M, Mochamat, Cuhls H, et al. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev 2015; :CD006788.
  147. Rabkin JG, Wagner GJ, Rabkin R. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatry 2000; 57:141.
  148. Knapp PE, Storer TW, Herbst KL, et al. Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Am J Physiol Endocrinol Metab 2008; 294:E1135.
  149. Rabkin JG, Wagner GJ, McElhiney MC, et al. Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol 2004; 24:379.
  150. Wagner GJ, Rabkin R. Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial. J Clin Psychiatry 2000; 61:436.
  151. Breitbart W, Rosenfeld B, Kaim M, Funesti-Esch J. A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Arch Intern Med 2001; 161:411.
  152. Rabkin JG, McElhiney MC, Rabkin R, McGrath PJ. Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study. J Clin Psychiatry 2010; 71:707.
  153. Rabkin JG, McElhiney MC, Rabkin R. Treatment of HIV-related fatigue with armodafinil: a placebo-controlled randomized trial. Psychosomatics 2011; 52:328.
  154. O'Brien K, Nixon S, Glazier RH, Tynan AM. Progressive resistive exercise interventions for adults living with HIV/AIDS. Cochrane Database Syst Rev 2004; :CD004248.
  155. O'Brien K, Nixon S, Tynan AM, Glazier R. Aerobic exercise interventions for adults living with HIV/AIDS. Cochrane Database Syst Rev 2010; :CD001796.
  156. Dworkin MS, Williamson JM, Adult/Adolescent Spectrum of HIV Disease Project. AIDS wasting syndrome: trends, influence on opportunistic infections, and survival. J Acquir Immune Defic Syndr 2003; 33:267.