Depression and Adherence to Antiretroviral Therapy in Low-, Middle- and High-Income Countries: A Systematic Review and Meta-Analysis
We investigated the associations between depressive symptoms and adherence to antiretroviral therapy (ART) among people living with HIV (PLHIV). We searched the PubMed, EMBASE and Cochrane CENTRAL databases for studies that reported an association between depression and adherence to ART as a primary or secondary outcome. We used a random-effect model to pool the risk estimates from the individual studies. The odds ratio (OR) with their 95 % CIs were used as summary estimates. Of 2861 citations, 111 studies that recruited 42,366 PLHIV met our inclusion criteria. When reported, the rate of PLHIV with depressive symptoms ranged from 12.8 to 78 % and the proportion of PLHIV who achieved good adherence (≥80 %) ranged from 20 to 98 %. There were no significant differences in rate of depressive symptoms in PLHIV by country income group; however, the proportion of PLHIV who achieved good adherence was significantly higher in lower-income countries (as defined in the 2012 World Bank Country Income Groups) (pooled rate = 86 %) compared to higher-income countries (pooled rate = 67.5 %; p < .05). We found that the likelihood of achieving good ART adherence was 42 % lower among those with depressive symptoms compared to those without (pooled OR = 0.58, 95 % CI 0.55 to 0.62). The relationship between depressive symptoms and adherence to ART was consistent across the country’s income group, study design and adherence rates. We found that the magnitude of the association significantly decreases with more recent publications and increasing study sample size. The higher the prevalence of depressive symptoms of PLHIV recruited in the studies, the lower the likelihood of achieving good adherence to ART. In conclusion, the likelihood of achieving good adherence was lower among those with depressive symptoms compared to those without.
KeywordsHIV ART Depression Adherence Co-infections and comorbidity
We thank Ms. Joyce Snyder, Pittsburgh University, Department of Epidemiology, Pittsburgh, PA, USA; and Ms. Debbie Harrison, Stellenbosch University, Department of Medicine and Center for Infectious Diseases, Cape Town, South Africa, for administrative support.
The US National Institutes for Allergy and Infectious Disease-National Institutes of Health (NIAID-NIH), AIDS Clinical Trial Group (ACTG), Stellenbosch University (SU)-Clinical Trial Unit (CTU) Award: 2UM1AI069521-08 (J. B. N.); the US NIH-Fogarty International Center (FIC)/Health Resources and Services Administration (HRSA)/US President Emergency Plan for AIDS Relief (PEPFAR) Grant Award, T84HA21652-01-00 for Medical Education Partnership Initiative (MEPI) (J. B. N.); the European Developing Countries Clinical Trial Partnership (EDCTP) Senior Fellowship Award: TA-08-40200-021 (J. B. N.); the Wellcome Trust Southern Africa Consortium for Research Excellence (SACORE): WT087537MA (J. B. N.); FAS Marie Curie International Post Doc: 2012–0064 (O. A. U.); The MGH Global Psychiatric Clinical Research Training Program: NIH T32MH093310 (J. F. M); K24MH094214 (S. A. S.).
The agencies had no role in the conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript. The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the NIH, the US Department of Health and Human Services, PEPFAR, HRSA and the Wellcome Trust.
Compliance with Ethics Guidelines
Conflict of Interest
Olalekan A. Uthman, Jessica F. Magidson, Steven A. Safren, Jean B. Nachega declare that they have no conflict of interest
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
- 14.Nachega JB, Uthman OA, Anderson J, Peltzer K, Wampold S, Cotton MF, et al. Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis. AIDS. 2012;26(16):2039–52. doi: 10.1097/QAD.0b013e328359590f.PubMedGoogle Scholar
- 15.Lipsey MW, Wilson DB. Practical meta-analysis. Thousand Oaks: Sage; 2001.Google Scholar
- 16.Borenstein M, Hedges LV, Higgins JPT. Introduction to meta-analysis (Statistics in practice). Chichester: Wiley; 2009.Google Scholar
- 24.Amberbir A, Woldemichael K, Getachew S, Girma B, Deribe K. Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia. BMC Pub Health. 2008;8(265). doi: 10.1186/1471-2458-8-265.
- 25.Amico KR, Konkle-Parker DJ, Cornman DH, Barta WD, Ferrer R, Norton WE, et al. Reasons for ART non-adherence in the Deep South: adherence needs of a sample of HIV-positive patients in Mississippi. AIDS Care Psychol Sociol Med Asp AIDS/HIV. 2007;19(10):1210–8. doi: 10.1080/09540120701426516.Google Scholar
- 29.Arnsten JH, Li X, Mizuno Y, Knowlton AR, Gourevitch MN, Handley K et al. Factors associated with antiretroviral therapy adherence and medication errors among HIV-infected injection drug users. J Acquir Immune Defic Syndr. 2007;46(SUPPL. 2):S64-S71. doi: 10.1097/QAI.0b013e31815767d6.
- 31.Barfod TS, Gerstoft J, Rodkjaer L, Pedersen C, Nielsen H, Moller A, et al. Patients' answers to simple questions about treatment satisfaction and adherence and depression are associated with failure of HAART: a cross-sectional survey.[Erratum appears in AIDS Patient Care STDS. 2005 Aug;19(8):544]. AIDS Patient Care STDS. 2005;19(5):317–25.PubMedGoogle Scholar
- 37.Byakika-Tusiime J, Crane J, Oyugi JH, Ragland K, Kawuma A, Musoke P, et al. Longitudinal antiretroviral adherence in HIV+ Ugandan parents and their children initiating HAART in the MTCT-Plus family treatment model: role of depression in declining adherence over time. AIDS Behav. 2009;13 Suppl 1:82–91. doi: 10.1007/s10461-009-9546-x.PubMedGoogle Scholar
- 40.Catz SL, Heckman TG, Kochman A, DiMarco M. Rates and correlates of HIV treatment adherence among late middle-aged and older adults living with HIV disease. Psychol Health Med. 2001;6(1):47–58.Google Scholar
- 47.Demas P, Schoenbaum EE, Hirky AE, Wills TA, Doll LS, Hartel DM, et al. The relationship of HIV treatment acceptance and adherence to psyschosocial factors among injecting drug users. AIDS Behav. 1998;2(4):283–91.Google Scholar
- 49.Do HM, Dunne MP, Kato M, Pham CV, Nguyen KV. Factors associated with suboptimal adherence to antiretroviral therapy in Viet Nam: a cross-sectional study using audio computer-assisted self-interview (ACASI). BMC Infectious Diseases. 2013;13(1). doi: 10.1186/1471-2334-13-154.
- 50.Do NT, Phiri K, Bussmann H, Gaolathe T, Marlink RG, Wester CW. Psychosocial factors affecting medication adherence among HIV-1 infected adults receiving combination antiretroviral therapy (cART) in Botswana. AIDS Res Hum Retrovir. 2010;26(6):685–91. doi: 10.1089/aid.2009.0222.PubMedCentralPubMedGoogle Scholar
- 53.Farley J, Miller E, Zamani A, Tepper V, Morris C, Oyegunle M, et al. Screening for hazardous alcohol use and depressive symptomatology among HIV-infected patients in Nigeria: prevalence, predictors, and association with adherence. J Int Assoc Phys AIDS Care (Chic). 2010;9(4):218–26. doi: 10.1177/1545109710371133.Google Scholar
- 59.Hilerio CM, Martinez J, Zorrilla CD, Torres R. Posttraumatic stress disorder symptoms and adherence among women living with HIV. Ethn Dis. 2005;15(4 SUPPL. 5).Google Scholar
- 61.Horberg MA, Silverberg MJ, Hurley LB, Towner WJ, Klein DB, Bersoff-Matcha S, 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(3):384–90. doi: 10.1097/QAI.0b013e318160d53e.PubMedGoogle Scholar
- 62.Horne R, Cooper V, Gellaitry G, Date HL, Fisher M. Patients' perceptions of highly active antiretroviral therapy in relation to treatment uptake and adherence: the utility of the necessity-concerns framework. J Acquir Immune Defic Syndr. 2007;45(3):334–41. doi: 10.1097/QAI.0b013e31806910e3.PubMedGoogle Scholar
- 64.Ironson G, O'Cleirigh C, Fletcher MA, Laurenceau JP, Balbin E, Klimas N, et al. Psychosocial factors predict CD4 and viral load change in men and women with human immunodeficiency virus in the era of highly active antiretroviral treatment. Psychosom Med. 2005;67(6):1013–21.PubMedCentralPubMedGoogle Scholar
- 65.Johnson MO, Catz SL, Remien RH, Rotheram-Borus MJ, Morin SF, Charlebois E, et al. Theory-guided, empirically supported avenues for intervention on HIV medication nonadherence: findings from the Healthy Living Project. AIDS Patient Care STDS. 2003;17(12):645–56. doi: 10.1089/108729103771928708.PubMedGoogle Scholar
- 67.Kacanek D, Jacobson DL, Spiegelman D, Wanke C, Isaac R, Wilson IB. Incident depression symptoms are associated with poorer HAART adherence: a longitudinal analysis from the nutrition for healthy living study. J Acquir Immune Defic Syndr. 2010;53(2):266–72. doi: 10.1097/QAI.0b013e3181b720e7.PubMedCentralPubMedGoogle Scholar
- 71.Kekwaletswe C, Morojele N, Nkosi S. Depression, alcohol use and adherence to antiretroviral therapy (ART). 6th International AIDS Society Conference on HIV Pathogenesis and Treatment. Rome; 2011.Google Scholar
- 80.Markos E, Worku A, Davey G. Adherence to ART in PLWHA at Yirgalem hospital, South Ethiopia. Ethiop J Health Dev. 2008;22:174–9.Google Scholar
- 84.Moss AR, Hahn JA, Perry S, Charlebois ED, Guzman D, Clark RA et al. Adherence to highly active antiretroviral therapy in the homeless population in San Francisco: a prospective study. Clin Infect Dis. 39(8):1190–8. doi: 10.1086/424008.
- 88.Nachega J, Morroni C, Ram M, Efron E, Chaisson RE, Maartens G. Impact of concurrent TB treatment on ART adherence and liver toxicity in South African adults. [Poster#883]. 18th Conference on retroviruses and opportunistic infection; Boston; 2011.Google Scholar
- 90.Nakimuli–Mpungu E, Munyaneza G. Depression alcohol abuse and disclosure of HIV serostatus among rural HIV-positive individuals in western Uganda. Neurobehav HIV Med. 2011;3:19–25.Google Scholar
- 97.Palepu A, Horton NJ, Tibbetts N, Meli S, Samet JH. Uptake and adherence to highly active antiretroviral therapy among HIV-infected people with alcohol and other substance use problems: the impact of substance abuse treatment. Addiction (Abingdon, England). 2004. doi: 10.1111/j.1360-0443.2003.00670.x.
- 102.Ramadhani HO, Thielman NM, Landman KZ, Ndosi EM, Gao F, Kirchherr JL, et al. Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;45(11):1492–8. doi: 10.1086/522991.Google Scholar
- 103.Roux P, Carrieri MP, Villes V, Dellamonica P, Poizot-Martin I, Ravaux I, et al. The impact of methadone or buprenorphine treatment and ongoing injection on highly active antiretroviral therapy (HAART) adherence: evidence from the MANIF2000 cohort study. Addiction. 2008;103(11):1828–36. doi: 10.1111/j.1360-0443.2008.02323.x.PubMedGoogle Scholar
- 104.Royal SW, Kidder DP, Patrabansh S, Wolitski RJ, Holtgrave DR, Aidala A, et al. Factors associated with adherence to highly active antiretroviral therapy in homeless or unstably housed adults living with HIV. AIDS Care Psychol Sociol Med Asp AIDS/HIV. 2009;21(4):448–55. doi: 10.1080/09540120802270250.Google Scholar
- 115.Stone VE, Jordan J, Tolson J, Miller R, Pilon T. Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy: self-report of the relative importance of multiple attributes of highly active antiretroviral therapy (HAART) regimens in predicting adherence. J Acquir Immune Defic Syndr. 2004;36(3):808–16.PubMedGoogle Scholar
- 118.Tucker JS, Burnam MA, Sherbourne CD, Kung FY, Gifford AL. Substance use and mental health correlates of nonadherence to antiretroviral medications in a sample of patients with human immunodeficiency virus infection. Am J Med. 2003;114(7):573–80. doi: 10.1016/S0002-9343%2803%2900093-7.PubMedGoogle Scholar
- 124.Wagner JH, Justice AC, Chesney M, Sinclair G, Weissman S, Rodriguez-Barradas M. Patient- and provider-reported adherence: toward a clinically useful approach to measuring antiretroviral adherence. J Clin Epidemiol. 2001;1:S91–8.Google Scholar
- 126.Webb MS, Vanable PA, Carey MP, Blair DC. Medication adherence in HIV-infected smokers: The mediating role of depressive symptoms. AIDS Educ Prev. 2009;21(SUPPL. 3):94–105. doi: 10.1521/aeap.2009.21.3_supp.94.
- 134.Pence BW, Gaynes BN, Williams Q, Modi R, Adams J, Quinlivan EB, et al. Assessing the effect of Measurement-Based Care depression treatment on HIV medication adherence and health outcomes: rationale and design of the SLAM DUNC Study. Contemp Clin Trials. 2012;33(4):828–38. doi: 10.1016/j.cct.2012.04.002.PubMedCentralPubMedGoogle Scholar
- 136.Nachega JB, Parienti JJ, Uthman OA, Gross R, Dowdy DW, Sax PE, et al. Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: a meta-analysis of randomized controlled trials. Clin Infect Dis Off Publ Infect Dis Soc Am. 2014;58(9):1297–307. doi: 10.1093/cid/ciu046.Google Scholar
- 137.Safren SA, O'Cleirigh C, Tan JY, Raminani SR, Reilly LC, Otto MW, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol Off J Div Health Psychol Am Psychol Assoc. 2009;28(1):1–10. doi: 10.1037/a0012715.Google Scholar
- 138.Safren SA, O'Cleirigh CM, Bullis JR, Otto MW, Stein MD, Pollack MH. Cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected injection drug users: a randomized controlled trial. J Consult Clin Psychol. 2012;80(3):404–15. doi: 10.1037/a0028208.PubMedCentralPubMedGoogle Scholar