AIDS and Behavior

, Volume 17, Issue 1, pp 41–60 | Cite as

A Meta-Analysis of Adherence to Antiretroviral Therapy and Virologic Responses in HIV-Infected Children, Adolescents, and Young Adults

  • Shoshana Y. KahanaEmail author
  • Jennifer Rohan
  • Susannah Allison
  • Thomas W. Frazier
  • Dennis Drotar
Substantive Review


The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) <100, VL < 400, and continuously measured VL. The analyses included 5,344 HIV+ children, adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report indices elicited very small to small magnitude effects across both VL < 100 and VL < 400 outcomes and combined informant reporting (youth/adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials reported smaller relationships between adherence and categorical clinical outcomes, such that year of publication significantly negatively correlated with VL < 100 (r = −.71(14), p < .005) and VL < 400 (r = −.43(26), p < .02). The data suggest that the magnitude of the relationship between ART adherence and virologic outcomes among heterogeneous samples of HIV+ children, adolescents and young adults varies across virologic outcomes and may be affected by moderating sample and methodological factors. Methodological and research recommendations for the interpretation of the current findings as well as for future HIV adherence related research are presented.


Adherence Pediatric Youth Young adult Antiretroviral therapy Highly active HIV 



The authors would like to acknowledge Marvin Belzer, M.D., Pim Brouwers, Ph.D., Richard Jenkins, Ph.D., Lisa Hightow-Weidman, M.D., MPH, Bill G. Kapogiannis, M.D., Michael J. Stirratt, Ph.D., and Christopher Sarampote, Ph.D. for their aid in the conceptualization of the current study; Justin Drott, B.A. for his editorial assistance; and all study authors who responded to inquiries about relevant papers. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of NIDA or any of the sponsoring organizations, agencies, or the US government.


  1. 1.
    Drotar D, Bonner MS. Influences on adherence to pediatric asthma treatment: a review of correlates and predictors. J Dev Behav Pediatr. 2009;30(6):574–82.PubMedCrossRefGoogle Scholar
  2. 2.
    Pritchard MT, Butow PN, Stevens MM, Duley JA. Understanding medication adherence in pediatric acute lymphoblastic leukemia: a review. J Pediatr Hematol Oncol. 2006;28(12):816–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Simoni JM, Montgomery A, Martin E, New M, Demas PA, Rana S. Adherence to antiretroviral therapy for pediatric HIV infection: a qualitative systematic review with recommendations for research and clinical management. Pediatrics. 2007;119(6):e1371–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Steele RG, Grauer D. Adherence to antiretroviral therapy for pediatric HIV infection: review of the literature and recommendations for research. Clin Child Fam Psychol Rev. 2003;6(1):17–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Vreeman RC, Wiehe SE, Pearce EC, Nyandiko WM. A systematic review of pediatric adherence to antiretroviral therapy in low- and middle-income countries. Pediatr Infect Dis J. 2008;27(8):686–91.PubMedCrossRefGoogle Scholar
  6. 6.
    Haberer J, Mellins C. Pediatric adherence to HIV antiretroviral therapy. Curr HIV/AIDS Rep. 2009;6(4):194–200.PubMedCrossRefGoogle Scholar
  7. 7.
    Sutcliffe CG, van Dijk JH, Bolton C, Persaud D, Moss WJ. Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa. Lancet Infect Dis. 2008;8(8):477–89.PubMedCrossRefGoogle Scholar
  8. 8.
    Ciaranello AL, Chang Y, Margulis AV, et al. Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Clin Infect Dis. 2009;49(12):1915–27.PubMedCrossRefGoogle Scholar
  9. 9.
    Sabin CA, Smith CJ, d’Arminio Monforte A, et al. Response to combination antiretroviral therapy: variation by age. AIDS. 2008;22(12):1463–73.PubMedCrossRefGoogle Scholar
  10. 10.
    Marston M, Zaba B, Salomon JA, Brahmbhatt H, Bagenda D. Estimating the net effect of HIV on child mortality in African populations affected by generalized HIV epidemics. J Acquir Immune Defic Syndr. 2005;38(2):219–27.PubMedCrossRefGoogle Scholar
  11. 11.
    Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004;364(9441):1236–43.PubMedCrossRefGoogle Scholar
  12. 12.
    Hedges LV, Olkin I. Statistical methods for meta-analysis. San Diego: Academic Press; 1985.Google Scholar
  13. 13.
    Lipsey MW, Wilson DB. Practical meta-analysis. Thousand Oaks: Sage Publications; 2001.Google Scholar
  14. 14.
    Prendergast A, Mphatswe W, Tudor-Williams G, et al. Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. AIDS. 2008;22(11):1333–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Belzer ME, Fuchs DN, Luftman GS, Tucker DJ. Antiretroviral adherence issues among HIV-positive adolescents and young adults. J Adolesc Health. 1999;25(5):316–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years—United States, 2008. MMWR Recomm Rep. 2008;57(RR-10):1–12.PubMedGoogle Scholar
  17. 17.
    World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. 2007, Geneva, Switzerland: WHO Press. Available at
  18. 18.
    Rosenthal R. Meta-analytic procedures for social research (Revised ed.). Newbury Park: Sage; 1991.Google Scholar
  19. 19.
    Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10(1):101–29.CrossRefGoogle Scholar
  20. 20.
    Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale: Lawrence Erlbaum Associates; 1988.Google Scholar
  21. 21.
    Ahoua L, Guenther G, Rouzioux C, et al. Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda. BMC Pediatr. 2011;11:67.PubMedCrossRefGoogle Scholar
  22. 22.
    Bagenda A, Barlow-Mosha L, Bagenda D, Sakwa R, Fowler MG, Musoke PM. Adherence to tablet and liquid formulations of antiretroviral medication for paediatric HIV treatment at an urban clinic in Uganda. Ann Trop Paediatr. 2011;31(3):235–45.PubMedCrossRefGoogle Scholar
  23. 23.
    Burack G, Gaur S, Marone R, Petrova A. Adherence to antiretroviral therapy in pediatric patients with human immunodeficiency virus (HIV-1). J Pediatr Nurs. 2010;25(6):500–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Charles M, Noel F, Leger P, et al. Survival, plasma HIV-1 RNA concentrations and drug resistance in HIV-1-infected Haitian adolescents and young adults on antiretrovirals. Bull World Health Organ. 2008;86(12):970–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Davies MA, Boulle A, Fakir T, Nuttall J, Eley B. Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study. BMC Pediatr. 2008;8:34.PubMedCrossRefGoogle Scholar
  26. 26.
    Elise A, France AM, Louise WM, et al. Assessment of adherence to highly active antiretroviral therapy in a cohort of African HIV-infected children in Abidjan, Cote d’Ivoire. J Acquir Immune Defic Syndr. 2005;40(4):498–500.PubMedCrossRefGoogle Scholar
  27. 27.
    Flynn PM, Rudy BJ, Douglas SD, et al. Virologic and immunologic outcomes after 24 weeks in HIV type 1-infected adolescents receiving highly active antiretroviral therapy. J Infect Dis. 2004;190(2):271–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Garvie PA, Wilkins ML, Kolivas ED, Young JC. Multimethod adherence assessment in children with perinatally acquired HIV-1: The influence of off-schedule dosing in predicting biological markers. Pediatr Infect Dis J. 2009;29(4):1–3.Google Scholar
  29. 29.
    Giacomet V, Albano F, Starace F, et al. Adherence to antiretroviral therapy and its determinants in children with human immunodeficiency virus infection: a multicentre, national study. Acta Paediatr. 2003;92(12):1398–402.PubMedCrossRefGoogle Scholar
  30. 30.
    Gibb DM, Goodall RL, Giacomet V, McGee L, Compagnucci A, Lyall H. Adherence to prescribed antiretroviral therapy in human immunodeficiency virus-infected children in the PENTA 5 trial. Pediatr Infect Dis J. 2003;22(1):56–62.PubMedCrossRefGoogle Scholar
  31. 31.
    Gody JC, Charpentier C, Mbitikon O, et al. High prevalence of antiretroviral drug resistance mutations in HIV-1 non-B subtype strains from African children receiving antiretroviral therapy regimen according to the 2006 revised WHO recommendations. J Acquir Immune Defic Syndr. 2008;49(5):566–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Haberer JE, Cook A, Walker AS, et al. Excellent adherence to antiretrovirals in HIV+ Zambian children is compromised by disrupted routine, HIV nondisclosure, and paradoxical income effects. PLoS One. 2011;6(4):e18505.PubMedCrossRefGoogle Scholar
  33. 33.
    Hammami N, Nöstlinger C, Hoerée T, Lefèvre P, Jonckheer T, Kolsteren P. Integrating adherence to highly active antiretroviral therapy into children’s daily lives: a qualitative study. Pediatrics. 2004;114(5):e591–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Hansudewechakul R, Jourdain G, Plangraun N. A comprehensive programme to strengthen adherence to antiretroviral drug therapy and achieve virological control in HIV infected children in Thailand. Vulnerable Child Youth Stud. 2006;1(2):180–91.CrossRefGoogle Scholar
  35. 35.
    Katko E, Johnson GM, Fowler SL, Turner RB. Assessment of adherence with medications in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2001;20(12):1174–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Khan M, Song X, Williams K, Bright K, Sill A, Rakhmanina N. Evaluating adherence to medication in children and adolescents with HIV. Arch Dis Child. 2009;94(12):970–3.PubMedCrossRefGoogle Scholar
  37. 37.
    LePrevost M, Green H, Flynn J, et al. Adherence and acceptability of once daily Lamivudine and abacavir in human immunodeficiency virus type-1 infected children. Pediatr Infect Dis J. 2006;25(6):533–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Macdonell KE, Naar-King S, Murphy DA, Parsons JT, Harper GW. Predictors of medication adherence in high risk youth of color living with HIV. J Pediatr Psychol. 2010;35(6):593–601.PubMedCrossRefGoogle Scholar
  39. 39.
    Martin S, Elliott-DeSorbo DK, Wolters PL, et al. Patient, caregiver and regimen characteristics associated with adherence to highly active antiretroviral therapy among HIV-infected children and adolescents. Pediatr Infect Dis J. 2007;26(1):61–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Mellins CA, Brackis-Cott E, Dolezal C, Abrams EJ. The role of psychosocial and family factors in adherence to antiretroviral treatment in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2004;23(11):1035–41.PubMedCrossRefGoogle Scholar
  41. 41.
    Muller AD, Jaspan H, Lewis A, et al. A comparison of multiple methods to measure adherence in young children. Poster presentation at the 3rd NIMH/IAPAC international conference on HIV treatment. 2008; Jersey City, NJ.Google Scholar
  42. 42.
    Muller AD, Bode S, Myer L, Roux P, von Steinbüchel N. Electronic measurement of adherence to pediatric antiretroviral therapy in South Africa. Pediatr Infect Dis J. 2008;27(3):257–62.PubMedCrossRefGoogle Scholar
  43. 43.
    Murphy DA, Wilson CM, Durako SJ, Muenz LR, Belzer M. Antiretroviral medication adherence among the REACH HIV-infected adolescent cohort in the USA. AIDS Care. 2001;13(1):27–40.PubMedCrossRefGoogle Scholar
  44. 44.
    Naar-King S, Frey M, Harris M, Arfken C. Measuring adherence to treatment of paediatric HIV/AIDS. AIDS Care. 2005;17(3):345–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Naar-King S, Templin T, Wright K, Frey M, Parsons JT, Lam P. Psychosocial factors and medication adherence in HIV-positive youth. AIDS Patient Care STDS. 2006;20(1):44–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Nachega JB, Hislop M, Nguyen H, et al. Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa. J Acquir Immune Defic Syndr. 2009;51(1):65–71.PubMedCrossRefGoogle Scholar
  47. 47.
    Park J, Nachman S. The link between religion and HAART adherence in pediatric HIV patients. AIDS Care. 2010;22(5):556–61.PubMedCrossRefGoogle Scholar
  48. 48.
    Reddington C, Cohen J, Baldillo A, et al. Adherence to medication regimens among children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2000;19(12):1148–53.PubMedCrossRefGoogle Scholar
  49. 49.
    Reitz C, Coovadia A, Ko S, et al. Initial response to protease-inhibitor-based antiretroviral therapy among children less than 2 years of age in South Africa: effect of cotreatment for tuberculosis. J Infect Dis. 2010;201(8):1121–31.PubMedCrossRefGoogle Scholar
  50. 50.
    Rongkavilit C, Naar-King S, Chuenyam T, Wang B, Wright K, Phanuphak P. Health risk behaviors among HIV-infected youth in Bangkok, Thailand. J Adolesc Health. 2007;40(4):351–8.CrossRefGoogle Scholar
  51. 51.
    Rudy BJ, Murphy DA, Harris DR, Muenz L, Ellen J. Patient-related risks for nonadherence to antiretroviral therapy among HIV-infected youth in the United States: a study of prevalence and interactions. AIDS Patient Care STDS. 2009;23(3):185–94.PubMedCrossRefGoogle Scholar
  52. 52.
    Rudy BJ, Murphy DA, Harris DR, Muenz L, Ellen J. Prevalence and interactions of patient-related risks for nonadherence to antiretroviral therapy among perinatally infected youth in the United States. AIDS Patient Care STDS. 2010;24(2):97–104.PubMedCrossRefGoogle Scholar
  53. 53.
    van Dijk JH, Sutcliffe CG, Munsanje B, et al. HIV-infected children in rural Zambia achieve good immunologic and virologic outcomes two years after initiating antiretroviral therapy. PLoS One. 2011;6(4):e19006.PubMedCrossRefGoogle Scholar
  54. 54.
    Van Dyke RB, Lee S, Johnson GM, et al. Reported adherence as a determinant of response to highly active antiretroviral therapy in children who have human immunodeficiency virus infection. Pediatrics. 2002;109(4):e61.PubMedCrossRefGoogle Scholar
  55. 55.
    Wamalwa DC, Farquhar C, Obimbo EM, et al. Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial. J Int AIDS Soc. 2009;12(8):1–10.Google Scholar
  56. 56.
    Wiener L, Riekert K, Ryder C, Wood LV. Assessing medication adherence in adolescents with HIV when electronic monitoring is not feasible. AIDS Patient Care STDS. 2004;18(9):527–38.PubMedCrossRefGoogle Scholar
  57. 57.
    Williams PL, Storm D, Montepiedra G, et al. Predictors of adherence to antiretroviral medications in children and adolescents with HIV infection. Pediatrics. 2006;118(6):e1745–57.PubMedCrossRefGoogle Scholar
  58. 58.
    Orwin RG. A fail-safe N for effect size in meta-analysis. J Educ Stat. 1983;8(2):157–9.CrossRefGoogle Scholar
  59. 59.
    Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. October 14, 2011, pp 1–167. Available at
  60. 60.
    Cambiano V, Lampe FC, Rodger AJ, et al. Long-term trends in adherence to antiretroviral therapy from start of HAART. AIDS. 2010;24(8):1153–62.PubMedCrossRefGoogle Scholar
  61. 61.
    Mannheimer S, Friedland G, Matts J, Child C, Chesney M. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis. 2002;34(8):1115–21.PubMedCrossRefGoogle Scholar
  62. 62.
    Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet. 2010;376(9755):1838–45.PubMedCrossRefGoogle Scholar
  63. 63.
    Pop-Eleches C, Thirumurthy H, Habyarimana JP, et al. Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders. AIDS. 2011;25(6):825–34.PubMedCrossRefGoogle Scholar
  64. 64.
    Rosenblum M, Deeks SG, van der Laan M, Bangsberg DR. The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy. PLoS One. 2009;4(9):e7196.PubMedCrossRefGoogle Scholar
  65. 65.
    Lima VD, Bangsberg DR, Harrigan PR, et al. Risk of viral failure declines with duration of suppression on highly active antiretroviral therapy irrespective of adherence level. J Acquir Immune Defic Syndr. 2010;55(4):460–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Bae JW, Guyer W, Grimm K, Altice FL. Medication persistence in the treatment of HIV infection: a review of the literature and implications for future clinical care and research. AIDS. 2011;25(3):279–90.PubMedCrossRefGoogle Scholar
  67. 67.
    Wilson IB, Carter AE, Berg KM. Improving the self-report of HIV antiretroviral medication adherence: is the glass half full or half empty? Curr HIV/AIDS Rep. 2009;6(4):177–86.PubMedCrossRefGoogle Scholar
  68. 68.
    Kahana S, Drotar D, Frazier T. Meta-analysis of psychological interventions to promote adherence to treatment in pediatric chronic health conditions. J Pediatr Psychol. 2008;33(6):590–611.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  • Shoshana Y. Kahana
    • 1
    Email author
  • Jennifer Rohan
    • 2
  • Susannah Allison
    • 3
  • Thomas W. Frazier
    • 4
  • Dennis Drotar
    • 5
  1. 1.Services Research Branch, Division of Epidemiology, Services and Prevention ResearchNational Institute on Drug AbuseBethesdaUSA
  2. 2.Cincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Infants, Children, and Adolescents ProgramNational Institute of Mental HealthBethesdaUSA
  4. 4.Cleveland ClinicCenter for Autism and ADHD CenterClevelandUSA
  5. 5.Division of Behavioral Medicine and Clinical PsychologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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