Associations Between Anxiety and Adherence to Antiretroviral Medications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

  • James WykowskiEmail author
  • Christopher G. Kemp
  • Jennifer Velloza
  • Deepa Rao
  • Paul K. Drain
Substantive Review


Untreated mental health disorders among people living with HIV (PLHIV) may prevent low- and middle-income countries (LMICs) from achieving the UNAIDS 90-90-90 targets. Anxiety disorders may be associated with decreased adherence to antiretroviral therapy (ART). We sought to review and meta-analyze studies estimating associations between anxiety and ART adherence in LMICs. We searched PubMed, PsychINFO, CINAHL and EMBASE for relevant studies published before July 18, 2018. We defined anxiety as reported anxiety scores from screening questionnaires or having a clinical diagnosis of an anxiety disorder, and poor ART adherence as missed doses, poor visit attendance, or scores from structured adherence questionnaires. We used a random effects model to conduct a meta-analysis for calculating a pooled odds ratio, and conducted sensitivity analyses by time on ART, anxiety evaluation method, and study region. From 472 screened manuscripts, thirteen studies met our inclusion criteria. Eleven studies were included in the meta-analysis. PLHIV who reported anxiety had 59% higher odds of poor ART adherence compared with those who did not report anxiety disorder (pooled odds ratio [pOR]: 1.59, 95% confidence interval [CI] 1.29–1.96, p < 0.001). When excluding PLHIV who initiated ART within 6 months, reported anxiety remained strongly associated with poor ART adherence (pOR: 1.61, 95% CI 1.18–2.20, p = 0.003). Among PLHIV in LMICs, reported anxiety was associated with poor ART adherence. This association persisted after the ART initiation period. Increased resources for mental health may be important for achieving virologic suppression in LMICs.


HIV Antiretroviral therapy Anxiety Adherence Low-income countries 



The authors would like to thank Adrienne Shapiro MD, PhD, Rachel Kubiak, Haylea Hannah, and the other members of the Drain TB/HIV Research Lab for their mentorship and editing support.


Infectious Disease Society of America Medical Scholars Program. Research reported in this publication was supported by the Infectious Disease Society of America Education & Research Foundation (IDSA ERF) and National Foundation for Infectious Diseases (NFID), the National Institute of Allergy and Infectious Disease of the National Institutes of Health (K23 AI108293), the National Institute for Mental Health (F31 MH112397), the Harvard University Center for AIDS Research (P30 AI060354), the Massachusetts General Hospital Executive Committee on Research, and the University of Washington/Fred Hutch Center for AIDS Research, an NIH-funded program under Award Number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other funding agencies.

Compliance with Ethical Standards

Conflict of interest

Authors Wykowski, Kemp, Velloza, Rao and Drain all declare they have no conflicts of interest to report.

Ethical Approval

This article does not contain any studies with human participants performed by any of the authors.


  1. 1.
    UNAIDS. 90-90-90 An ambitious treatment target to help end the AIDS epidemic. United Nations. 2014.Google Scholar
  2. 2.
    UNAIDS. Ending Aids Progress Towards the 90-90-90 Targets. Glob Aids Update. 2017;198. Available from:
  3. 3.
    Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine JP, et al. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys. JAMA. 2004;291(21):2581–90.Google Scholar
  4. 4.
    World Health Organization. Mental Health Atlas. Vol. 93, Bulletin of the World Health Organization. 2015.Google Scholar
  5. 5.
    Nakimuli-Mpungu E, Bass JK, Alexandre P, Mills EJ, Musisi S, Ram M, et al. Depression, alcohol use and adherence to antiretroviral therapy in sub-Saharan Africa: a systematic review. AIDS Behav. 2012;16(8):2101–8.Google Scholar
  6. 6.
    Wagner GJ, Ghosh-Dastidar B, Holloway IW, Kityo C, Mugyenyi P. Depression in the pathway of HIV antiretroviral effects on sexual risk behavior among patients in Uganda. AIDS Behav. 2012;16(7):1862–9.Google Scholar
  7. 7.
    Alemu H, Mariam DH, Tsui A, Ahmed S, Shewamare A. Effect of depressive symptoms and social support on weight and CD4 count increase at HIV clinic in Ethiopia. AIDS Care. 2012;24(7):866–76. Scholar
  8. 8.
    Krumme AA, Kaigamba F, Binagwaho A, Murray MB, Rich ML, Franke MF. Depression, adherence and attrition from care in HIV-infected adults receiving antiretroviral therapy. J Epidemiol Commun Health. 2015;69(3):284–9.Google Scholar
  9. 9.
    Marconi VC, Wu B, Hampton J, Ordonez CE, Johnson BA, Singh D, et al. Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic. AIDS Patient Care STDS. 2013;27(12):657–68.Google Scholar
  10. 10.
    Brandt C, Zvolensky MJ, Woods SP, Gonzalez A, Safren SA, O’Cleirigh CM. Anxiety symptoms and disorders among adults living with HIV and AIDS: a critical review and integrative synthesis of the empirical literature. Clin Psychol Rev. 2017;51:164–84.Google Scholar
  11. 11.
    Gonzalez A, Solomon SE, Zvolensky MJ, Miller CT. The interaction of mindful-based attention and awareness and disengagement coping with HIV/AIDS-related stigma in regard to concurrent anxiety and depressive symptoms among adults with HIV/AIDS. J Health Psychol. 2009;14(3):403–13.Google Scholar
  12. 12.
    Nilsson Schonnesson L, Diamond PM, Ross MW, Williams M, Bratt G. Baseline predictors of three types of antiretroviral therapy (ART) adherence: a 2-year follow-up. AIDS Care. 2006;18(4):407–14.Google Scholar
  13. 13.
    van Servellen G, Chang B, Garcia L, Lombardi E. Individual and system level factors associated with treatment nonadherence in human immunodeficiency virus-infected men and women. AIDS Patient Care STDS. 2002;16(6):269–81.Google Scholar
  14. 14.
    Wang Z. Chinese version of Zung’s self-rating anxiety scale. J Shanghai Psychiatry. 1984;2:73–4.Google Scholar
  15. 15.
    Rooks-Peck CR, Adegbite AH, Wichser ME, Ramshaw R, Mullins MM, Higa D, et al. Mental health and retention in HIV care: A systematic review and meta-analysis. Health Psychol. 2018;37(6):574–85.Google Scholar
  16. 16.
    Comulada WS, Rotheram-Borus MJ, Pequegnat W, Weiss RE, Desmond KA, Arnold EM, et al. Relationships over time between mental health symptoms and transmission risk among persons living with HIV. Psychol Addict Behav. 2010;24(1):109–18.Google Scholar
  17. 17.
    Mimiaga MJ, Biello K, Reisner SL, Crane HM, Wilson J, Grasso C, et al. Latent class profiles of internalizing and externalizing psychosocial health indicators are differentially associated with sexual transmission risk: Findings from the CFAR network of integrated clinical systems (CNICS) cohort study of HIV-infected men eng. Health Psychol. 2015;34(9):951–9.Google Scholar
  18. 18.
    Sikkema KJ, Dennis AC, Watt MH, Choi KW, Yemeke TT, Joska JA. Improving mental health among people living with HIV: a review of intervention trials in low- and middle-income countries. Glob Ment Heal. 2015;2:e19.Google Scholar
  19. 19.
    Rabkin JG. Prevalence of psychiatric disorders in HIV illness. Int Rev Psychiatry. 1996;8(2–3):157–66. Scholar
  20. 20.
    APA. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.Google Scholar
  21. 21.
    Radzniwan R, Alyani M, Aida J, Khairani O, Nik Jaafar N, Tohid H. Psychological status and its clinical determinants among people living with HIV/AIDS (PLWHA) in Northern Peninsular Malaysia. HIV AIDS Rev. 2016;15:141–6.Google Scholar
  22. 22.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.Google Scholar
  23. 23.
    Veritas Health Innovation. Covidence Systematic Review Software. Melborne, Australia. 2018.
  24. 24.
    The World Bank. The World Bank In Middle Income Countries.
  25. 25.
    Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111.Google Scholar
  26. 26.
    Calvetti P, Giovelli P, Gauer G, de Moraes J. Psychosocial factors associated with adherence to treatment and quality of life in people living with HIV/AIDS in Brazil. J Bras Psiquiatr. 2014;63:8–15.Google Scholar
  27. 27.
    Amirkhanian Y, Kelly J, DiFranceisco W, Kuznetsova A, Tarima S, Yakovlev A, et al. Predictors of HIV care engagement, antiretroviral medication adherence, and viral suppression among people living with hiv infection in St. Petersburg, Russia. AIDS Behav. 2016;22:791–9.Google Scholar
  28. 28.
    Panigrahi M, Swain T, Mohanty S. Nonadherence to anti-HIV medication is associated with higher level of anxiety: experience from a tertiary care hospital of Odisha. Indian J Pharmacol. 2015;47:672–5.Google Scholar
  29. 29.
    Campos LN, Guimarães M, Remien R. Anxiety and depression symptoms as risk factors for non-adherence to antiretroviral therapy in Brazil. AIDS Behav. 2008;14:1–11.Google Scholar
  30. 30.
    Qiao S, Li X, Zhou Y, Shen Z, Tang Z, Stanton B. The role of enacted stigma in parental HIV disclosure among HIV-infected parents in China. AIDS Care. 2015;27:28–35.Google Scholar
  31. 31.
    Prasithsirikul W, Chongthawonsatid S, Ohata P, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV-infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care. 2017;29:299–305.Google Scholar
  32. 32.
    Nguyen N, Tran B, Hwang L, Markham C, Swartz M, Vidrine J, et al. Effects of cigarette smoking and nicotine dependence on adherence to antiretroviral therapy among HIV-positive patients in Vietnam. AIDS Care. 2016;28:359–64.Google Scholar
  33. 33.
    Nel A, Kagee A. The relationship between depression, anxiety and medication adherence among patients receiving antiretroviral treatment in South Africa. AIDS Care. 2013;25:948–55.Google Scholar
  34. 34.
    Joshi B, Chauhan S, Pasi A, Kulkarni R, Sunil N, Bachani D, et al. Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India. Indian J Med Res. 2014;140:84–95.Google Scholar
  35. 35.
    Guimarães M, Rocha G, Camos L, de Freitas F, Gualberto F, Teixeira R, et al. Difficulties reported by HIV-infected patients using antiretroviral therapy in Brazil. Clinics (Sao Paulo). 2008;63:165–72.Google Scholar
  36. 36.
    Adejumo O, Oladeji B, Akpa O, Malee K, Baiyewu O, Ogunniyi A, et al. Psychiatric disorders and adherence to antiretroviral therapy among a population of HIV-infected adults in Nigeria. Int J STD AIDS [Internet]. 2016;27:938–49.Google Scholar
  37. 37.
    Yunusa MA, Njoku CH, Obembe A. Self-reported adherence to treatment: a study of socioeconomic factors and psychiatric morbidity among male and female patients with HIV infection in Sokoto, Nigeria. Running title: Treatment adherence, socioeconomic factors and psychiatric morbidity in H. Niger J Med. 2014;23:33–9.Google Scholar
  38. 38.
    Pefura-Yone E, Soh E, Kengne A, Balkissou AD, Kuaban C. Non-adherence to antiretroviral therapy in Yaounde: prevalence, determinants and the concordance of two screening criteria. J Infect Public Health. 2013;6:307–15.Google Scholar
  39. 39.
    Tao J, Qian H, Kipp A, Ruan Y, Shepherd B, Amico K, et al. Effects of depression and anxiety on antiretroviral therapy adherence among newly diagnosed HIV-infected Chinese MSM. AIDS. 2017;31:401–6.Google Scholar
  40. 40.
    Yu Y, Luo D, Chen X, Huang Z, Wang M, Xiao S. Medication adherence to antiretroviral therapy among newly treated people living with HIV. BMC Public Health. 2018;18(1):1–8.Google Scholar
  41. 41.
    Pokhrel KN, Sharma VD, Pokhrel KG, Neupane SR, Mlunde LB, Poudel KC, et al. Investigating the impact of a community home-based care on mental health and anti-retroviral therapy adherence in people living with HIV in Nepal : a community intervention study. BMC Infec. 2018;18:1–9.Google Scholar
  42. 42.
    Nguyen NTP, Tran BX, Hwang LY, Markham CM, Swartz MD, Vidrine JI, et al. Effects of cigarette smoking and nicotine dependence on adherence to antiretroviral therapy among HIV-positive patients in Vietnam. AIDS Care. 2015;28:1–6.Google Scholar
  43. 43.
    Joshi B, Chauhan S, Pasi A, Kulkarni R, Sunil N, Bachani D, et al. Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India. Indian J Med Res. 2014;140(1):84–95.Google Scholar
  44. 44.
    Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56(6):893–7.Google Scholar
  45. 45.
    Spitzer RL, Kroenke K, Williams JBW, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7.Google Scholar
  46. 46.
    Stern AF. The hospital anxiety and depression scale. Occup Med (Lond). 2014;64(5):393–4.Google Scholar
  47. 47.
    Zung WW. A rating instrument for anxiety disorders. Psychosomatics. 1971;12(6):371–9.Google Scholar
  48. 48.
    Rabin R, Oemar M, Oppe M, Janssen B, Herdman M. EQ-5D-5L user guide. Basic information on how to use the EQ-5D-5L instrument. 2015.Google Scholar
  49. 49.
    World Health Organization. mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-Specialized Health Settings: Mental Health Gap Action Programme (mhGAP). mhGAP Interv Guid Ment Neurol Subst Use Disord Non-Specialized Heal Settings Ment Heal Gap Action Program. 2010;1–121.Google Scholar
  50. 50.
    Barthel D, Barkmann C, Ehrhardt S, Bindt C. Psychometric properties of the 7-item Generalized Anxiety Disorder scale in antepartum women from Ghana and Cote d’Ivoire. J Affect Disord. 2014;169:203–11.Google Scholar
  51. 51.
    Chibanda D, Verhey R, Gibson LJ, Munetsi E, Machando D, Rusakaniko S, et al. Validation of screening tools for depression and anxiety disorders in a primary care population with high HIV prevalence in Zimbabwe. J Affect Disord. 2016;198:50–5.Google Scholar
  52. 52.
    Sweetland AC, Belkin GS, Verdeli H. Measuring Depression and Anxiety in Sub-Saharan Africa. Depress Anxiety. 2014;31(3):223–32.Google Scholar
  53. 53.
    Tennyson RL, Kemp CG, Rao D. Challenges and strategies for implementing mental health measurement for research in low-resource settings. Int Health. 2016;8(6):374–80.Google Scholar
  54. 54.
    Jiamsakul A, Kerr SJ, Kiertiburanakul S, Azwa I, Zhang F, Chaiwarith R, et al. Early suboptimal ART adherence was associated with missed clinical visits in HIV-infected patients in Asia. AIDS Care. 2018;30:1–7.Google Scholar
  55. 55.
    Berg KM, Arnsten JH. Practical and conceptual challenges in measuring antiretroviral adherence. J Acquir Immune Defic Syndr. 2006;43(Suppl 1):S79–87.Google Scholar
  56. 56.
    WHO. WHO Prequalification of In Vitro Diagnostics PUBLIC REPORT Product : Xpert ® HIV-1 Viral Load with GeneXpert ® Dx, GeneXpert ® Infinity- 48, GeneXpert ® Infinity-48 s and GeneXpert ® Infinity-80 WHO reference numbers : PQDx 0192-070-00, PQDx 0193-070-00. World Health Organization. 2017.Google Scholar
  57. 57.
    Dorward J, Drain PK, Garrett N. Point-of-care viral load testing and differentiated HIV care. Lancet HIV. 2018;5(1):e8–9.Google Scholar
  58. 58.
    Steele GI. Development and validation of the Xhosa translations of the Beck inventories: 2. Item analysis, internal consistency, and factor analysis. J Psychol Afr. 2008;18:217.Google Scholar
  59. 59.
    Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke J, et al. The Composite International Diagnostic Interview. An epidemiologic Instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Arch Gen Psychiatry. 1988;45(12):1069–77.Google Scholar
  60. 60.
    Gureje O, Lasebikan VO, Kola L, Makanjuola VA. Lifetime and 12-month prevalence of mental disorders in the Nigerian Survey of Mental Health and Well-Being. Br J Psychiatry. 2006;188(5):465–71.Google Scholar
  61. 61.
    Gureje O, Obikoya B. The GHQ-12 as a screening tool in a primary care setting. Soc Psychiatry Psychiatr Epidemiol. 1990;25(5):276–80.Google Scholar
  62. 62.
    Gureje O, Ogunniyi A, Kola L, Afolabi E. Functional disability among elderly Nigerians: results from the Ibadan Study of Ageing. J Am Geriatr Soc. 2006;54(11):1784–9.Google Scholar
  63. 63.
    Tran BX, Ohinmaa A, Nguyen LT. Quality of life profile and psychometric properties of the EQ-5D-5L in HIV/AIDS patients. Health Qual Life Outcomes. 2012;10:132.Google Scholar
  64. 64.
    Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and depression scale: an updated literature review. J Psychosom Res. 2002;52(2):69–77.Google Scholar
  65. 65.
    Botega NJ, Bio MR, Zomignani MA, Garcia C Jr, Pereira WA. Mood disorders among inpatients in ambulatory and validation of the anxiety and depression scale HAD. Rev Saude Publica. 1995;29(5):355–63.Google Scholar
  66. 66.
    Lam CLK, Pan PC, Chan AWT, Chan SY, Munro C. Can the Hospital Anxiety and Depression (HAD) Scale be used on Chinese elderly in general practice? Fam Pract. 1995;12(2):149–54. Scholar
  67. 67.
    Abiodun OA. A validity study of the Hospital Anxiety and Depression Scale in general hospital units and a community sample in Nigeria. Br J Psychiatry. 1994;165(5):669–72.Google Scholar
  68. 68.
    Nilchaikovit T, Lotrakul M, Phisansuthideth U. Development of Thai version of Hospital Anxiety and Depression Scale in cancer patients. J Psychiatr Assoc Thail. 1996;41:18–30.Google Scholar
  69. 69.
    Lane DA, Jajoo J, Taylor RS, Lip GY, Jolly K. Cross-cultural adaptation into Punjabi of the english version of the hospital anxiety and depression scale. BMC Psychiatry. 2007;7:5.Google Scholar
  70. 70.
    Thomas BC, Devi N, Sarita GP, Rita K, Ramdas K, Hussain BM, et al. Reliability and validity of the Malayalam hospital anxiety and depression scale (HADS) in cancer patients. Indian J Med Res. 2005;122(5):395–9.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicine, School of MedicineUniversity of WashingtonSeattleUSA
  2. 2.Department of Global Health, School of Public HealthUniversity of WashingtonSeattleUSA
  3. 3.Department of Epidemiology, School of Public HealthUniversity of WashingtonSeattleUSA
  4. 4.Department of Psychiatry and Behavioral SciencesUniversity of WashingtonSeattleUSA

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