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Curr HIV/AIDS Rep. Author manuscript; available in PMC 2013 Mar 25.
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PMCID: PMC3607373

Antiretroviral Adherence Interventions: Translating Research Findings to the Real World Clinic


The success of potent combination antiretroviral therapy (ART) for HIV infection is compromised primarily by failure to maintain optimal levels of adherence over the long term. Recent reviews suggest behavioral interventions to promote ART adherence can have significant effects, but these tend to be small and to diminish over time; sustained improvements in biomarkers are particularly elusive. In this article, we update current reviews, focusing specifically on the 13 studies evaluating behavioral interventions to promote ART adherence published since September 2007. We describe the range of intervention strategies employed and qualitatively summarize findings of their efficacy. In conclusion, we consider implications and offer strategies for enhancing adherence in clinic-based HIV care prior to ART initiation, at initiation, and over the course of treatment.

Keywords: HIV/AIDS, ART, Adherence, Interventions, Review


Soon after the introduction of combination antiretroviral therapy (ART) in the late 1990s, patient adherence emerged as the Achilles’ heel in these otherwise potent regimens [1, 2]. Without strict attention to dosing schedules and dietary restrictions, the efficacy of ART was severely compromised [3, 4]. Indeed, perhaps never before in medical history has a therapeutic regimen required such strict lifetime adherence with such devastating consequences for nonadherence. New formulations have dramatically reduced pill burden to as little as one pill taken once daily, yet adherence remains challenging and is still a long-term predictor of viral suppression. Moreover, inconsistent adherence to simplified regimens continues to threaten treatment options for individuals who develop resistance to known agents.

Given the devastating consequences of suboptimal adherence to ART, including rapid onset of viremia and the development of resistant virus that is transmittable to others [5], an unprecedented amount of research has been undertaken to understand and promote ART adherence. A meta-analysis indicated that among the 24 behavioral interventions to promote antiretroviral adherence published through 2004 [6], there was a “small” but significant average effect (d = 0.35; odds ratio [OR] = 1.88; P < 0.05) on adherence, which was larger in studies that enrolled participants thought to have adherence difficulties. Focusing solely on RCTs, Simoni et al. [7] found that across 19 studies, participants in the intervention arm were about 50% more likely than those in the control arm to achieve 95% adherence (OR = 1.50; 95% CI, 1.16–1.94) and 25% more likely to have an undetectable HIV-1 RNA viral load (VL; OR = 1.25, 95% CI, 0.99–1.59). A recent update extended coverage of the literature through September 2007 to include 48 studies (6,810 participants total) and similarly found support for behavioral interventions targeting improvements in adherence (d = 0.28; OR = 1.66; 95% CI, 1.54–1.78), with somewhat larger effects in studies targeting poor adherers and smaller effects in studies with longer monitoring periods (over 45 weeks) or that targeted ART-naïve patients [8•].

In this article, we highlight recent advances in ART-adherence intervention strategies, focusing specifically on reports evaluating behavioral interventions to promote ART adherence published since September 2007. We describe the range of intervention strategies, with an emphasis on the most successful approaches. In concluding, we suggest how the findings might be incorporated into ongoing primary HIV clinic care.

Selection and Description of Studies

A search of PubMed (Medline) and PsychInfo with the terms “intervention and HIV” and “adherence/compliance and ART/HAART/ARV” yielded 70 peer-reviewed non-redundant articles published in English between September 1, 2007 and October 31, 2009. Among these, 13 were selected for review based on their evaluation of a behavioral intervention to promote ART adherence. Note that three studies in the initial search detailed aspects of adherence-promotion interventions but were excluded from the review because the evaluation of the intervention was initially reported prior to the inclusion date criterion [9•, 10, 11].

The 13 studies are described in Table 1. Nine were conducted in the United States, with the others conducted in Brazil, Canada, China, and Mozambique. Targeted samples included both men and women (11 studies, n = 1849, in addition to the 7018 beneficiary claims reviewed in Hirsh et al. [12•]) and women only (two studies, n = 248). Participants’ ART history varied, with six studies targeting those who were switching regimens and/or were ART naïve, three studies of ART-experienced participants, and four studies of those with a full range of ART backgrounds, from naïve to highly experienced. Samples were largely drawn from a general HIV primary care clinic population, although some studies specifically targeted drug and alcohol users or other high-risk groups.

Table 1
Recent studies of behavioral interventions to promote antiretroviral adherence

Intervention strategies and modalities were heterogeneous, including nurse-delivered individual counseling, peer group and individual peer support, facilitated group sessions, phone-based counseling, text/pager messaging, and data-driven approaches such as using electronic dose monitoring (EDM) as an intervention tool. The total duration of interventions varied from 1 months to 15 months. Most studies lacked any follow-up assessments beyond immediate post-intervention; in others, follow-up was 6 months, 9–12 months, or 18–24 months. Exposure included as-needed patient or provider-initiated phone contacts, tapered daily pages, regularly scheduled individual sessions, and groups that met rarely (monthly) or frequently (5 days per week). Six of the interventions used theoretical approaches to guide the development of intervention content, mainly drawing from well-known theories of health behavior changes (eg, Information, Motivation, Behavioral Skills Model [13, 14], Transtheoretical Model [15], and Self-regulation Theory [16]). In five of the interventions, empirically supported approaches to facilitate health behavior change were specified (eg, motivational interviewing, cognitive-behavioral techniques, problem solving, and harm reduction approaches).

Study methodology to evaluate outcomes was generally rigorous, with ten randomized controlled trials. Most employed an intent-to-treat analysis followed by more specific or qualified outcome investigations. Nine studies included some self-reported measure of adherence, typically a recall of missed doses over the prior several days. Four studies used EDM, and three included a pharmacy refill or claims-based assessment of adherence; none used pill counts. Three studies evaluated their outcomes on multiple measures of adherence; the others used one. The majority of studies incorporated biomarkers as outcome indicators: CD4 only (one study), VL only (three studies), or both (five studies).

Overall, most studies demonstrated a clear or qualified impact on adherence. Only two failed to find support for any adherence metric, and both of these involved fairly intensive interventions in the control arm (Sampaio-Sa et al. [17] studied intervention contrasting an Information, Motivation, Behavioral Skills model-based educational workshop with a group video-based control of similar content, and Whol et al. [18] examined intensive weekly case management contrasted with standard case management). Six studies demonstrated efficacy in primary analyses and an additional five evaluations provided qualified support (eg, efficacy within a given group, for select adherence measures, or for some portion of the monitoring period). As indicated in Table 1, successful interventions included adherence approaches incorporated into pharmacy usual care [12•], one-on-one and group-based peer support [19, 20]; peer-delivered modified directly observed therapy [21]; patient-centered or motivational interviewing-based approaches delivered by a nurse in person or by telephone [2224]; and one-on-one approaches covering specific aspects of adherence [25, 26]. Additionally, Koenig et al. [27] reported positive outcomes on adherence for their multicomponent intervention that involved both the patient-participant and an individual within the patient’s support system identified as an adherence support person in individual and group sessions delivered by trained nurses. Sabin et al. [28] reported support for their approach of training participants in EDM use and using EDM data printouts with patients to review their adherence patterns, identify missed or outside of dose time doses, and explore barriers around those events. As noted in Table 1, the initial positive impact of an intervention on adherence outcomes often was attenuated at follow-up when interventions were discontinued.

Of the nine studies evaluating biomarker outcomes, three demonstrated clear support and three demonstrated qualified support for intervention efficacy. All of these studies reported generally positive findings in terms of ART adherence measures. Among the three studies failing to note effects on biological outcomes, two had demonstrated positive adherence outcomes [24, 28] and one [17] found no effects on biomarkers or adherence.

Implications for Clinic-Based HIV Primary Care

Building upon past literature, the more recent published work targeting adherence offers additional guidance in terms of specific strategies that might be considered for inclusion in clinical practice. It is important to note that although we can select strategies that may be effective from the current literature, individual or discrete strategies are rarely evaluated outside of the context of larger comprehensive intervention approaches. What the most recent activity in adherence intervention design clearly signals is a movement towards compendium or multicomponent interventions that mobilize several support strategies and delivery modalities. Adopting a single approach from a multifaceted program (eg, making phone calls to check in with patients on their adherence, suggesting an adherence support person be identified within a patient’s social network to help him or her with adherence, or creating an accessible 24-h adherence call-in line for use in clinic) may compromise its overall efficacy. Thus, independent strategies presented here are not clearly established or demonstrated as independent active ingredients, but they may nonetheless offer approaches that might be cautiously considered for incorporation in clinical care.

With this proviso in mind, we present in Table 2 some strategies to consider, based both on the studies reviewed here as well as the accumulated recommendations of previous reviews of this literature [29•]. These are grouped in terms of the pressing treatment and adherence tasks at hand when individuals are preparing to initiate ART, when they commence a regimen, and as they continue over time. These are somewhat artificial distinctions, as ART regimens are changed and individuals cycle among adherence phases. Overall, the strategies emphasize adopting a multidisciplinary team-based approach to anticipating challenges in adherence and directly assessing and addressing it with a diverse array of strategies, some brief and inexpensive (sensitively assessing adherence as part of routine clinical care) and other resource-intensive and long term (providing ongoing case management to address situational barriers such as mental health issues, housing instability, and substance abuse). Past studies suggest ongoing support is needed. Ideally, strategies should be considered for delivery over time and not delivered solely for intensive periods.

Table 2
Strategies for promoting antiretroviral adherence

Clinics must weigh the intensity of contact required with respect to their financial and personnel resources. In the face of increasingly complex interventions (intensive one-on-one counseling, frequent professionally facilitated group sessions, automated text messaging), many clinics may find themselves ill equipped. Unfortunately, researchers only rarely provide cost-benefit data on adherence interventions; only one of the 13 studies reviewed here did so [21]. Issues germane to initial start-up costs, training required, person hours required, supplies to be purchased (eg, pill boxes, EDM devices), services maintained (eg, cell phone monthly fees, text messaging services, toll-free phone lines), and implementation support over time are all critical to consider. Cost considerations are even more influential in resource-constrained settings.


Published reports of behavioral interventions both recently and in the past decade suggest it is possible to intervene in ways that promote antiretroviral medication adherence, but effects are generally small and transitory and there are no clearly demonstrated simple strategies. Multifaceted, long-term, and flexible approaches are needed to support adherence behavior, which itself is complex and dynamic. As Sandelowski et al. [30] has recently noted, most of the interventions have an “individualistic and rationalistic” slant. Intervention strategies need to be refined and evaluated that target all the different domains of factors empirically demonstrated to impact antiretroviral adherence. These include societal factors as encompassing as stigma, situational factors such as clinic location and convenience, and even regimen characteristics such as less complicated, more easily tolerated regimens.

While awaiting further research, perhaps with outcomes on comparative effectiveness, clinicians should consider monitoring and evaluating their own strategies as part of quality assurance procedures. These results of approaches based in actual clinical and not research settings will provide a perspective on feasibility and implementation currently lacking in the published literature on randomized controlled trials. Finally, focusing on medication adherence is necessary and appropriate but should not divert attention from efforts to retain patients in care once initiated. In fact, it is likely that interventions and strategies intended to enhance overall engagement in HIV care may prove particularly useful in both retaining individuals in care and encouraging frank discussions about ART adherence difficulties with providers. Finally, future research and practice should consider intervention approaches that address the “lived experience” of individuals in HIV care, which includes adherence challenges for those on ART but also other life priorities that influence treatment-related decisions. Only in full collaboration with patients, in recognition of their often trying life circumstances, can providers form partnerships with the best prospects for optimal health outcomes.


Disclosure No potential conflicts of interest relevant to this article were reported.

Contributor Information

Jane M. Simoni, Department of Psychology, University of Washington, Campus Box 351525, Seattle, WA 98195-1525, USA, ude.wu@inomisj..

K. Rivet Amico, Center for Health, Intervention & Prevention, University of Connecticut, 2006 Hillside Road, Storrs, CT 06269, USA, ten.hcraeserhtlaehdeilppa@ocimatevir.

Laramie Smith, Center for Health, Intervention & Prevention, Department of Psychology, University of Connecticut, 2006 Hillside Road, Unit 1248, Storrs, CT 06269, USA, ude.nnocu@htimS.eimaraL.

Kimberly Nelson, Department of Psychology, University of Washington, Campus Box 351525, Seattle, WA 98195-1525, USA, ude.notgnihsaw.u@6noslenk.


Papers of particular interest, published recently, have been highlighted as:

• Of importance

1. Chesney MA, Morin M, Sherr L. Adherence to HIV combination therapy. Soc Sci Med. 2000;50:1599–1605. [PubMed]
2. Williams AB. Adherence to highly active antiretroviral therapy. Nurs Clin North Am. 1999;34:113–129. [PubMed]
3. Mannheimer S, Friedland G, Matts J, et al. The consistency of adherence to an antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis. 2002;34:1115–1121. [PubMed]
4. Paterson DL, Swindells S, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133:21–30. [PubMed]
5. Ross L, Lim LM, Wine B, et al. Prevalence of antiretroviral drug resistance and resistance-associated mutations in antiretroviral therapy-naïve HIV-infected individuals from 40 United States cities. HIV Clin Trial. 2007;8:1–8. [PubMed]
6. Amico KR, Harman JJ, Johnson BT. Efficacy of antiretroviral therapy adherence interventions: a research synthesis of trials, 1996 to 2004. J Acquir Immune Defic Syndr. 2006;41:285–297. [PubMed]
7. Simoni JM, Pearson CR, Pantalone DW, et al. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load: a meta-analytic review of randomized controlled trials. J Acquir Immune Defic Syndr December. 2006;43(Suppl 1):S23–S35. [PMC free article] [PubMed]
8. Amico KR, Harman JJ, O’Grady M, Johnson B. Research synthesis of ART adherence interventions: A synthesis of published adherence intervention outcomes research from 1996 to September. Paper presented at 4th Annual HIV Treatment Adherence Conference of the International Association of Providers in AIDS Care; April 2009; Miami, FL. A meta-analysis of published studies of antiretroviral adherence promotion interventions through September 2007 that systematically considers their efficacy.
9. Cote J, Godin G, Ramirez-Garcia P, et al. Program development for enhancing adherence to antiretroviral therapy among persons living with HI. AIDS Patient Care STD. 2008;22:965–975. [PubMed] An excellent example of intervention mapping and its application in the development of theory-based adherence interventions.
10. Lester RT, Mills EJ, Kariri A, et al. The HAART cell phone adherence trial (WelTel Kenya I): a randomized controlled trial protocol. Trials. 2009;10:87–95. [PMC free article] [PubMed]
11. Nishigaki M, Shimada M, Ideda K, et al. Process and contents of telephone concultations between registered nurses and clients with HIV/AIDS in Japan. J Assoc Nurses AIDS Care. 2007;18:85–96. [PubMed]
12. Hirsch JD, Rosenquist A, Best BM, Miller TA, et al. Evaluation of the first year of a pilot program in a community pharmacy: HIV/AIDS Medication Therapy Managment for Medi-Cal Beneficiaries. J Manag Care Pharmacy. 2009;15:32–41. [PubMed] This intervention approach was at the level of providing incentives through state funding for pharmacies to adopt more comprehensive approaches to adherence.
13. Fisher JD, Fisher WA. Theoretical approaches to individual-level change in HIV risk behavior. In: Peterson R, DiClemente J, editors. Handbook of HIV Prevention. New York: Klewer Academic/Plenum; 2000. pp. 3–55.
14. Fisher JD, Fisher WA, Amico KR, Harman JJ. An information-motivation-behavioral skills model fo adherence to antoretroviral therapy. Health Psychology. 2006;25:262–473. [PubMed]
15. Prochazka JO, DiClemente CC. Stages of change in the modification of problem behaviors. In: Herson M, Miller PM, Eisler R, editors. Progress in Behavior Change Modification. New York: Wadsworth Publishing; 1992. pp. 184–218.
16. Rosenbaum MA. A model for research on self-regulation: reducing the schism between behaviorism and general psychology. In: Eifert GH, Evans IM, editors. Unifying Behavior Therapy. New York: Springer Publishing Co.; 1990. pp. 126–149.
17. Sampaio-Sa M, Page-Shafer K, Bangsberg DR, et al. 100% Adherence study: educational workshops vs. video sessions to improve adherence among ART-naïve patients in Salvador, Brazil. AIDS Behav. 2008;12:S54–S62. [PubMed]
18. Whol AR, Garland WH, Witt MD, et al. An adherence-focused case management intervention for HIV-positive patients in a public care setting. J HIV/AIDS Social Serv. 2009;8:80–94.
19. Deering KN, Shannon K, Sinclair H, et al. Piloting a peer-driven intervention model to increase access and adherence to antiretroviral therapy and HIV care among street-entrenched HIV-positive women in Vancouver. AIDS Patient Care STD. 2009;23:603–609. [PubMed]
20. Simoni JM, Huh D, Frick PA, et al. Peer support and pager messaging to promote antiretroviral modifying therapy in Seattle: a randomized controlled Trial. J Acquir Immune Defic Syndr. 2009;52:499–507. [PMC free article] [PubMed]
21. Pearson CR, Micek MA, Simoni JM, et al. Randomized control trial of peer-delivered, modified directly observed therapy for HAART in Mozambique. J Acquir Immune Defic Syndr. 2007;46:238–244. [PMC free article] [PubMed]
22. DiIorio C, McCarty F, Resnicow K, et al. Using motivational interviewing to promote adherence to antiretroviral medications: a randomized controlled study. AIDS Care. 2008;20:273–283. [PMC free article] [PubMed]
23. Parsons JT, Colub SA, Rosof E, Holder C. Motivational interviewing and Cognitive-Behavioral interventiont o improve HIV medication adherence among hazardous drinkers: a randomized controlled trial. J Acquir Immune Defic Syndr. 2007;46:443–450. [PMC free article] [PubMed]
24. Reynolds NR, Testa MA, Su M, et al. Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial. J Acquir Immune Defic Syndr. 2008;47:62–68. [PubMed]
25. Johnson MO, Charlebois E, Morin SF, et al. Effects of a behavioral intervention on antiretroviral medication adherence among people living with HIV: The Healty Living Project randomized controlled study. J Acquir Immune Defic Syndr. 2007;46:574–580. [PMC free article] [PubMed]
26. Lopez E, Jones DL, Ishii M, et al. HIV mediation adherence and substance use: The Smartest Women’s Project. Am J Infect Dis. 2007;3:240–247. [PMC free article] [PubMed]
27. Koenig LJ, Pals SL, Bush T, et al. Raondomized controlled trila of an interventiont o prevent adherence failure among HIV-infected patients initiating antiretroviral therapy. Health Psychol. 2008;27:159–169. [PubMed]
28. Sabin LL, Bachman DeSilva M, Hamer DH, et al. Using electronic drug monitor feedback to improve adherence to antiretroviral therapy among HIV-positive patients in China. AIDS Behav. 2009 Sep 22; (Epub ahead of print). [PMC free article] [PubMed]
29. Simoni JS, Amico KR, Pearson CR, Malow RM. Strategies for promoting adherence to antiretroviral therapy: a review of the liteature. Curr Infect Dis Rep. 2008;10:515–521. [PubMed] This is a qualitative review of adherence intervention studies that highlights some of the most recent and innovative research in the areas of patient education and case management, modified early direct observed therapy, contingency management, and interventions emphasizing social support.
30. Sandelowski M, Voils CI, Chang Y, Lee E. A systematic review comparing antiretroviral adherence descriptive intervention studies conducted in the USA. AIDS Care. 2009;21:953–966. [PMC free article] [PubMed]
31. Segal-Isaacson CJ, Tobin JN, Weiss SM, et al. Improving dietary habits in disadvantaged women with HIV/AIDS: The SMART/EST Women’s Project. AIDS Behav. 2006;10:659–670. [PMC free article] [PubMed]
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