Skip Navigation LinksHome > March 2014 - Volume 28 - Issue > Interventions to improve adherence to antiretroviral therapy...
doi: 10.1097/QAD.0000000000000252
Service delivery

Interventions to improve adherence to antiretroviral therapy: a rapid systematic review

Chaiyachati, Krisda H.a; Ogbuoji, Osondub; Price, Matthewb; Suthar, Amitabh B.c; Negussie, Eyerusalem K.c; Bärnighausen, Tillb,d

Free Access
Supplemental Author Material
Open Access Icon
Article Outline
Collapse Box

Author Information

aYale School of Medicine, New Haven

bDepartment of Global Health and Population, Harvard School of Public Health, Boston, USA

cHIV Department, World Health Organization, Geneva, Switzerland

dWellcome Trust Africa Centre for Health and Population Science, University of KwaZulu-Natal, Mtubatuba, South Africa.

Correspondence to Till Bärnighausen, 665 Huntington Avenue, Boston 02115, Boston, MA. Tel: +1 617 379 0372; fax: +1 617 432 6733; e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

Collapse Box


Introduction: Access to antiretroviral treatment (ART) has substantially improved over the past decade. In this new era of HIV as a chronic disease, the continued success of ART will depend critically on sustained high ART adherence. The objective of this review was to systematically review interventions that can improve adherence to ART, including individual-level interventions and changes to the structure of ART delivery, to inform the evidence base for the 2013 WHO consolidated antiretroviral guidelines.

Design: A rapid systematic review.

Methods: We conducted a rapid systematic review of the global evidence on interventions to improve adherence to ART, utilizing pre-existing systematic reviews to identify relevant research evidence complemented by screening of databases for articles published over the past 2 years on evidence from randomized controlled trials (RCTs). We searched five databases for both systematic reviews and primary RCT studies (Cochrane Library, EMBASE, MEDLINE, Web of Science, and WHO Global Health Library); we additionally searched for RCT studies. We examined intervention effectiveness by different study characteristics, in particular, the specific populations who received the intervention.

Results: A total of 124 studies met our selection criteria. Eighty-six studies were RCTs. More than 20 studies have tested the effectiveness of each of the following interventions, either singly or in combination with other interventions: cognitive-behavioural interventions, education, treatment supporters, directly observed therapy, and active adherence reminder devices (such as mobile phone text messages). Although there is strong evidence that all five of these interventions can significantly increase ART adherence in some settings, each intervention has also been found not to produce significant effects in several studies. Almost half (55) of the 124 studies investigated the effectiveness of combination interventions. Combination interventions tended to have effects that were similar to those of single interventions. The evidence base on interventions in key populations was weak, with the exception of interventions for people who inject drugs.

Conclusion: Tested and effective adherence-enhancing interventions should be increasingly moved into implementation in routine programme and care settings, accompanied by rigorous evaluation of implementation impact and performance. Major evidence gaps on adherence-enhancing interventions remain, in particular, on the cost-effectiveness of interventions in different settings, long-term effectiveness, and effectiveness of interventions in specific populations, such as pregnant and breastfeeding women.

Back to Top | Article Outline


Antiretroviral treatment (ART) has converted a highly fatal HIV infection into a chronic condition that requires lifelong care [1]. Within the past decade, worldwide access to ART has improved significantly, with almost 10 million people receiving ART by the end of 2012 [2]. In addition to its life-prolonging effects, ART can also reduce HIV transmission to uninfected people [3,4]. In this new era of HIV treatment, the continued success of ART will depend on improving our understanding of when to initiate therapy, creating continuity of care, and ensuring high treatment adherence. Adherence is the extent to which a person uses a medication according to medical recommendations, inclusive of timing, dosing, and consistency. Arguably, adherence is the most critical factor in ensuring ART success, because without good adherence, treatment failure is likely, leading to avoidable HIV-related morbidity and mortality. Additionally, imperfect adherence increases the risk of developing resistant HIV strains and transmitting the virus to others [5–7]. Because adherence behaviours and patterns can profoundly affect an individual's treatment response and potentially narrow future therapeutic options, improving and sustaining ART adherence is a critical component and priority of public health efforts.

People living with HIV and their care providers often face challenges in ensuring good adherence. A 2011 meta-analysis, which pooled ART adherence of 33 199 adults in 84 observational studies, reports that only 62% of individuals took at least 90% of their prescribed ART doses [8]. Given these adherence difficulties, effective, feasible and acceptable interventions to enhance ART adherence are urgently needed to ensure the continued success and clinical and financial sustainability of the global ART scale-up [9–11]. Multiple systematic reviews and meta-analysis of ART adherence-enhancing interventions have been conducted over the past few years, but these studies have often been limited to particular interventions, populations, or settings [12–16].

To inform the evidence base for the 2013 WHO consolidated guidelines on the Use Antiretroviral Drugs for Treating and Preventing HIV Infection [17], we conducted a rapid systematic review synthesizing the research results on ART adherence-enhancing interventions across intervention types, populations, and settings. Our review advances the existing literature in three ways: first, it is the most comprehensive compilation of the evidence on adherence-enhancing interventions to date; second, it allows evaluation of robustness of interventions across settings; and third, we indicate studies that focus on specific populations of particular interest because of comorbidities and other vulnerabilities that may interfere with their ability to adhere to ART. In addition to the contribution to the WHO 2013 consolidated guidelines, our review aims to provide a guide for ART programme managers, policy makers, and researchers to the portfolio of ART adherence-enhancing interventions for practice, policy and further study.

Back to Top | Article Outline


General methodology of rapid systematic reviews

We conducted a rapid systematic review of the global evidence on interventions to improve ART medication adherence. Rapid systematic reviews differ from traditional systematic reviews in that they utilize pre-existing systematic reviews to identify relevant research evidence in addition to screening databases for recent primary studies [18–21]. This practice is useful for making health policy decisions, because it allows examination of the evidence while ensuring that information is assimilated as fast as possible given prior work [18–24].

Using pre-existing systematic reviews to identify relevant primary articles reduces the time needed to identify the relevant body of evidence on a particular topic. However, given that the time required to conduct, complete, and publish a systematic review typically ranges from 1 to 2 years [20,22], synthesis solely based on pre-existing systematic reviews runs the danger of failing to incorporate evidence that has accrued over the most recent few years. We thus supplement our systematic review of systematic reviews, with a complete screening of databases of primary evidence, but – in order to maintain rapidity in the identification of primary studies – we constrained these searches to the past 2 years (2010–2012) and to randomized controlled trials (RCTs).

Back to Top | Article Outline
Search strategies

To identify systematic reviews, we conducted searches in the Cochrane Library, EMBASE, MEDLINE, Web of Science, and WHO Global Health Library (which includes both regional and global indices). The search algorithms are shown in Boxes A1 and A2 in the appendix ( Abstracts from conferences and meetings were excluded because they do not undergo the same level of peer review as published full-text articles and they do not provide the necessary references for extracting study-level data. Publications on adherence interventions were excluded if they were letters to the editor, editorials, commentaries, or opinion articles. We further excluded systematic reviews of interventions studying programme retention, efficacy of combination antiretrovirals (fixed or multiple medications), dosing strategies, or use of antiretrovirals for pre-existing or post-exposure prophylaxis. We did not limit our search to particular times, locations, or languages. Additionally, we searched, Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, Web of Science, and WHO Global Health Library for RCTs published between 1 September 2010 and 31 August 2012 that investigated interventions targeted towards improving ART adherence. To be included in this review, RCTs could report an adherence intervention as the primary or secondary aim or simply report adherence measurements in the presence of an intervention. Studies comparing or validating adherence measurement approaches without reporting on an adherence-enhancing intervention were excluded. We followed the reporting standards described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [25].

Back to Top | Article Outline
Study selection

Three investigators (K.C., M.P., and O.O.) worked independently, completing separate screenings of the literature. We screened titles and abstracts of studies that were identified in previous systematic reviews on the effectiveness of interventions aimed at increasing antiretroviral adherence; as well as titles and abstracts of records identified in the search of databases for RCTs investigating adherence interventions. All records were screened by two of the three reviewers; two reviewers have been found to be sufficient to carry out a high-quality systematic review [26]. The same reviewers used the inclusion and exclusion criteria to independently assess the full eligibility of studies identified in the databases. Reviewers were not blinded to study authors, conclusions, or outcomes, because blinding is complicated to implement and has been shown to have little effect on the quality of systematic reviews [27]. Once all potentially relevant full-text articles and abstracts were identified, the three reviewers achieved consensus regarding eligibility and extracted data onto a standardized extraction form. Where consensus was not possible, a fourth reviewer (T.B.) served as arbiter. After relevant systematic reviews were identified, we searched for the primary studies featured in these reviews and extracted the data from the studies. Data entry was compared, and discordant information was resolved by consensus through data checks and discussion between the data extractors. When necessary, the further reviewer (T.B.), who guided but was not directly involved in the primary data extraction process, was asked to mediate. Figures 1 and 2 show flowcharts of the study selection processes.

Fig. 1
Fig. 1
Image Tools
Fig. 2
Fig. 2
Image Tools
Back to Top | Article Outline
Data extraction

We organized the synthesis of results by adherence intervention type, that is, the actual intervention activity, such as directly observed therapy (DOT) or depression treatment. In addition to the intervention types, we extracted from the studies the following data: author and year of publication, study period, study design, country of study, population, source of information, and healthcare setting, in which the study took place; study duration, sample size, loss to follow-up, intervention, control group, adherence measure, and study results. Web Appendix, shows the study characteristics; Table 1 provides an overview of the different adherence-enhancing interventions that were tested in the studies and reports the results by outcome measure. We report on results for subjective adherence measures (self-report by patients), objective adherence measures (pill count, pharmacy refill, and electronic monitoring), and the biological correlates of adherence (viral load, CD4+ cell count, and change in body weight). A few studies report composite adherence indices incorporating information from several outcome measures. We do not include the results in terms of these outcome measures in our review, because the use of these indices is usually particular to one study, and all studies using indices also report results in terms of outcome based on individual measures.

Table 1
Table 1
Image Tools
Table 1
Table 1
Image Tools
Table 1
Table 1
Image Tools
Table 1
Table 1
Image Tools
Back to Top | Article Outline


A total of 124 studies met our selection criteria (Figures 1 and 2). These studies included 86 RCTs, 6 non-randomized controlled trials (NRCT), 19 before-after studies, 8 cohort studies, 4 case-control studies, and 1 cross-sectional study. Seventy-five studies were carried out in North America, 30 in Africa, 11 in Europe, 4 in Asia, 3 in Central and South America, and 2 in Australia. Publication intensity in studies testing ART adherence-enhancing interventions increased over time; each year before 2003 three or fewer articles were published, whereas in 2003 and thereafter, at least six articles were published each year and in many years more than 10 articles (Web Appendix,

Almost half (55) of the 124 studies investigated the effectiveness of combination interventions, that is, interventions that were composed of several clearly identifiable components. The most commonly tested interventions were cognitive-behavioural therapy (CBT) (60), followed by education (28), treatment supporters (26), DOT (20) and active reminder devices (20). The less commonly tested intervention types included structural interventions (such as changes in the person delivering ART, or in the location where ART were provided) (10), counselling (8), nutritional support (7), financial incentives (5), passive reminder devices (5), and drug use treatment (4). Active reminder devices included both telephone reminders and other technologies, such as pagers and pillboxes with in-built timers and alarms. Passive reminder devices included pillboxes and diary cards. Detailed information on intervention types and the interventions are shown in Table 1 . Commonly (in 29 studies), CBT, education or counselling were combined with other interventions. DOT, passive reminder devices, treatment supporters, nutritional support, and financial incentives were combined with other interventions in more than two-fifths of the studies, whereas the other interventions were less likely to be investigated in combination.

The synthetic picture that emerges becomes even more complex when the success of particular interventions is considered across different outcomes. Table 2 shows the distribution of outcome measures used across the 124 studies. Two-fifths of studies followed the general recommendation to use both outcomes that capture adherence (subjective measures-self-reported adherence levels, or objective measures – pill count, pharmacy refill, etc.), as well as those that capture the biological outcomes determined by adherence behaviour (viral load, CD4+ cell count, body weight). However, 16% of the studies measured adherence using only subjective outcomes. Overall, 72 of the 124 studies were found to generate significant positive effects as assessed by at least one outcome measure. But only 24 studies (or one-fifth) found significant positive effects in at least one biological and one (objective or subjective) ART-adherence measure. Combination interventions were not more or less likely to succeed in significantly improving outcomes than single interventions (P = 0.80 for having at least one positive effect across all outcomes; P = 0.55 for having at least one positive effect each for a biological and a subjective or objective adherence outcome).

Table 2
Table 2
Image Tools

Table 3 shows a synthesis of the study results by intervention type. In the case of combination interventions, each component intervention is counted separately. The table shows that for most interventions, at least three-fifths of the studies found a positive result for at least one outcome, but the proportion of studies finding positive results for both at least one biological and one subjective or objective adherence outcome is less than 50%.

Table 3
Table 3
Image Tools

Most studies (87) investigated adherence-enhancing interventions in the general population; the remainder focused on particular sub-populations. The most commonly researched sub-populations were persons who use drugs (PWUD), with 22 studies, followed by women (8 studies), children (4 studies), and persons with mental health disorders (2 studies). It is an important finding that despite overall small sample sizes, there were significant effects in 12 out of the 22 studies in PWUD. Syntheses of results by outcome measure are presented in Table 1 .

Back to Top | Article Outline


A large global evidence base on ART adherence-enhancing interventions – a total of 124 studies including 86 RCTs – provides important information for ART programming and planning. The field of ART adherence intervention research is developing rapidly and relatively more rapidly than research into ART access, linkage to care, and retention. The reason for this differential in research intensity within the overall field of HIV operations and health services research plausibly reflects the importance of ART adherence – we would prefer only to initiate patients on ART once we are able to ensure good ART adherence. It could also reflect the fact that ART adherence is more easily conducted than research into other aspects of ART services, because unlike studies of access, linkage, and retention, it only requires data collection in clinical cohorts and not in HIV-infected populations in communities. Whatever the reason for the intensity of the research on ART adherence-enhancing interventions, the speed of study implementation, analysis, and publication means that evidence syntheses will rapidly grow out of date. Our review provides an updated synthesis on the body of knowledge on the effectiveness of ART adherence-enhancing interventions.

Each of the following interventions has been tested in more than 20, mostly rigorous studies, either singly or in combination with other interventions: CBT, education, treatment supporters, DOT, and active adherence reminder devices (such as mobile phone text messages). Whereas there is strong evidence that all five of these interventions can significantly increase ART adherence in some settings, each intervention has also been found not to produce significant effects in several studies.

The 2013 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection describe the portfolio of adherence-enhancing interventions and recommends that ‘[M]obile phone text messages could be considered as a reminder tool for promoting adherence to ART as part of a package of adherence interventions’. This recommendation, as well as the descriptions of the evidence on other adherence-enhancing interventions in the guidelines, have been informed and are broadly supported by this systematic review. In addition – and with the caveats regarding context-specificity of findings discussed below – our review suggests that the other four interventions which have been widely tested in rigorous studies – CBT, education, treatment supporters, and DOT – warrant consideration by ART programme managers. Given the critical importance of adherence for the long-term individual and population-level success of ART, routine implementation of adherence-enhancing interventions should be considered.

Whereas the current evidence base provides a portfolio of interventions that have been shown to be effective in high-quality studies at least in some settings, adherence is a behaviour and as such is affected by culture and circumstance. The standard approaches to synthesizing evidence on effectiveness take on a different meaning when considering behavioural interventions as opposed to biological interventions. For behavioural interventions, consistency of causal effects across studies is an indicator of the degree of generalizability of an intervention effect to other settings rather than a measure of the degree to which an effect is ‘true’ as in the case of biological interventions.

We would expect that behavioural interventions that have been truly successful in one setting may not be effective in another one with different economic, social and behavioural barriers to adherence. Thus, health policy makers and programme planners need to carefully consider which adherence intervention to choose for routine implementation in a particular setting based on socio-cultural context, feasibility, acceptability, and health systems organization. The adherence-enhancing interventions identified in this review are likely to differ widely in implementation-relevant aspects, such as costs, human resources requirements, and scalability. Thus, other factors than the effectiveness evidence covered in this review will likely guide implementation decisions. For instance, DOT is labour-intensive and expensive, but it may be a good strategy for particular settings, for example, where patients can be easily reached, such as in hospitals or prisons. In contrast, some types of mobile phone text messaging interventions are comparatively inexpensive and do not require substantial human resources investment. As such, they may be a good option for general populations with high individual mobile phone coverage. Future meta-analyses of the contextual predictors of success of particular types of ART adherence interventions can further inform these choices. Additionally, it will be critical to monitor the performance of an adherence-enhancing intervention as it is introduced into routine ART services. Quasi-experimental designs, such as stepped wedge scale-up of adherence interventions across HIV clinics, might offer ‘natural’ opportunities for rigorous confirmation of effectiveness of the five interventions that the currently available body of evidence can increase adherence.

Whereas the global evidence on effectiveness of adherence-enhancing interventions is rich, our review has identified several important knowledge gaps that will be relevant for implementation decisions and should increasingly be filled with evidence from implementation science research. First, more evidence is needed to examine interventions that have shown promise in a few studies, but have only been tested in a limited range of settings. Our review finds that these interventions include the following: alternative health system structures for ART delivery, nutrition support, financial incentives, passive reminder devices (such as diary cards and compartmentalized pill boxes), drug use treatment, and anti-depressive treatment.

Second, comparative information on costs and cost-effectiveness of different effective adherence interventions is largely lacking, and when it is available, it is unclear in how far the costs assessed in a research setting are transferable to routine implementation situations. More cost-benefit studies as part of routine care are needed to provide this critical component for deciding between alternative effective adherence-enhancing interventions. Whereas several studies investigated combination interventions (see Table 1 ), differential effectiveness of alternative combination portfolios and interaction effects between different intervention components were rarely examined. It would seem plausible that combination adherence interventions will be particularly successful in increasing ART adherence because they commonly work through different pathways. However, our synthesis shows that combination interventions tend to be similarly likely to succeed in increasing ART adherence as single interventions. One reason for this finding could be that there is usually one dominant intervention within the combination, and the other interventions merely moderately enhance the effectiveness of the dominant intervention. Another reason could be that combination interventions are more difficult to implement than single interventions, and the achieved effects reflect these implementation difficulties. Future experimental research should increasingly use factorial designs that allow precise determinations of component intervention and interaction effects.

Third, the majority of studies establishing the effectiveness of adherence-enhancing interventions have lasted 2 years or less. Antiretroviral therapy, however, requires life-long adherence, spanning several decades for many patients. Long-term studies of ART adherence are urgently needed, and several teams are currently conducting follow-up studies, which will generate these important results [171–174]. Fourth, many studies are internally inconsistent in their findings, establishing significant effects on some outcomes (e.g. self-reported adherence), but not on other, related outcomes (e.g. immunological recovery). Technological improvements in capturing ART adherence could substantially improve the strength of the evidence regarding adherence behaviours, which tend to be unreliably reported [175] and may also not be accurately measureable with objective approaches, such medication event monitoring systems (MEMS), pill counts, or observation of pharmacy refill. Finally, as ART initiation is moving into earlier disease stages, average effects of ART adherence-enhancing interventions may change, because the population composition of people on ART changes. For instance, people initiating in earlier stages of HIV infection are less likely to have experienced recovery from advanced HIV-related disease and may thus require different cognitive and behavioural strategies and different technological support to ensure good adherence than people who initiated in late stages of the infection [176].

Our study has several limitations. Although it was a systematic review, it was ‘rapid’ in the methodological sense that it utilized existing systematic reviews to identify studies on adherence-enhancing interventions. Some of these systematic reviews may have missed relevant studies related to their objective and timeframe, and these studies could have also been missed in our review. In particular, the reliance on previous systematic reviews and our focused search of recent published results from RCTs imply that our synthesis is largely based on experimental studies, and that an additional review of quasi-experimental and non-experimental evidence may provide important additional insights. Additionally, our selection of reviews to identify primary studies under the rapid review methodology we employed excluded reviews that were not systematic, for example, narrative reviews; and our identification of records reporting primary RCT-based results was limited to studies whose primary aim was to enhance ART adherence. These selection criteria may have led to the exclusion of some interventions that can be of use in enhancing ART adherence, in particular, approaches to optimize ART regimens [177]. One example of such an intervention is single-tablet ART regimens, which have not been included in our review. Recently published reviews concluded that single-tablet regimens improve adherence and quality of life among ART patients in comparison to multi-tablet regimens [178,179].

Another unavoidable limitation of a systematic review based on formally published studies in a fast moving research field is that evidence that is emerging informally but has not yet been formally published will likely have been ignored, because academic writing, review and publication times in global health can last several years. These delays would have been particularly limiting if they led to the exclusion of completely novel interventions, for example, based on new technologies.

Although some studies were identified related to PWUD, data on other key populations were scarce. Given that these populations are disproportionately affected by the HIV epidemic and commonly face multiple challenges in ART adherence, future research focused on ART adherence-enhancing interventions tailored to key populations will be important, in particular, in sub-Saharan Africa, where such focused studies have been especially scarce.

In conclusion, we find a large and overall strong evidence base to support the claim that five interventions – CBT, education, treatment supporters, DOT, and active reminder devices – can improve ART adherence at least in some settings. These tested and effective adherence-enhancing interventions should increasingly be considered for routine implementation in ART programmes and health systems. However, rigorous on-going evaluation of the impact and performance of these interventions will be critical, because all interventions that proved effective in at least one setting were also found not to significantly increase adherence in at least one other setting. Significant evidence gaps on adherence-enhancing interventions need to be closed, including on cost-effectiveness, long-term effectiveness, and effectiveness in specific key populations.

Back to Top | Article Outline


Conflicts of interest

There are no conflicts of interest.

TB and KC were the lead authors, designing the study in close collaboration with EN and AS. KC, OO and MP scrutinized identified studies for eligibility and extracted data. TB and KC wrote the first draft of the manuscript; all authors contributed to the interpretation of the extracted data and critically reviewed the manuscript before submission.

Back to Top | Article Outline


1. Swendeman D, Ingram BL, Rotheram-Borus MJ. Common elements in self-management of HIV and other chronic illnesses: an integrative framework. AIDS Care 2009; 21:1321–1334.

2. WHO, UNICEF, UNAIDS. Global update on HIV treatment 2013: results, impact and opportunities. [Accessed 26 January 2014]

3. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365:493–505.

4. Tanser F, Bärnighausen T, Grapsa E, Zaidi J, Newell ML. High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science 2013; 339:966–971.

5. Press N, Tyndall MW, Wood E, Hogg RS, Montaner JS. Virologic and immunologic response, clinical progression, and highly active antiretroviral therapy adherence. J Acquir Immune Defic Syndr 2002; 31 (Suppl 3):S112–117.

6. Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS. Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 x 10(9) cells/L. Ann Intern Med 2003; 139:810–816.

7. Bangsberg DR, Perry S, Charlebois ED, Clark RA, Roberston M, Zolopa AR, et al. Nonadherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 2001; 15:1181–1183.

8. Ortego C, Huedo-Medina TB, Llorca J, Sevilla L, Santos P, Rodriguez E, et al. Adherence to highly active antiretroviral therapy (HAART): a meta-analysis. AIDS Behav 2011; 15:1381–1396.

9. Altice FL, Kamarulzaman A, Soriano VV, Schechter M, Friedland GH. Treatment of medical, psychiatric, and substance-use comorbidities in people infected with HIV who use drugs. Lancet 2010; 376:367–387.

10. Atkinson MJ, Petrozzino JJ. An evidence-based review of treatment-related determinants of patients’ nonadherence to HIV medications. AIDS Patient Care STDS 2009; 23:903–914.

11. Gordon CM. Commentary on meta-analysis of randomized controlled trials for HIV treatment adherence interventions. Research directions and implications for practice. J Acquir Immune Defic Syndr 2006; 43 (Suppl 1):S36–40.

12. Simoni JM, Pearson CR, Pantalone DW, Marks G, Crepaz N. 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 2006; 43 (Suppl 1):S23–35.

13. Ford N, Nachega JB, Engel ME, Mills EJ. Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials. Lancet 2009; 374:2064–2071.

14. Hart JE, Jeon CY, Ivers LC, Behforouz HL, Caldas A, Drobac PC, et al. Effect of directly observed therapy for highly active antiretroviral therapy on virologic, immunologic, and adherence outcomes: a meta-analysis and systematic review. J Acquir Immune Defic Syndr 2010; 54:167–179.

15. Rueda S, Park-Wyllie Laura Y, Bayoumi A, Tynan A-M, Antoniou T, Rourke S, et al. Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Cochrane Database of Systematic Reviews: John Wiley & Sons, Ltd; 2006.

16. Haddad M, Inch C, Glazier RH, Wilkins AL, Urbshott G, Bayoumi A, et al. Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Cochrane Database Syst Rev 2000; 3:CD001442.

17. World Health OrganizationConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2013; Geneva:World Health Organization, [Accessed 26 January 2014].

18. Smith V, Devane D, Begley CM, Clarke M. Methodology in conducting a systematic review of systematic reviews of healthcare interventions. BMC Med Res Methodol 2011; 11:15.

19. Whitlock EP, Lin JS, Chou R, Shekelle P, Robinson KA. Using existing systematic reviews in complex systematic reviews. Ann Intern Med 2008; 148:776–782.

20. Ganann R, Ciliska D, Thomas H. Expediting systematic reviews: methods and implications of rapid reviews. Implement Sci 2010; 5:56.

21. Bärnighausen T, Tanser F, Dabis F, Newell ML. Interventions to improve the performance of HIV health systems for treatment-as-prevention in sub-Saharan Africa: the experimental evidence. Curr Opin HIV AIDS 2012; 7:140–150.

22. Khangura S, Konnyu K, Cushman R, Grimshaw J, Moher D. Evidence summaries: the evolution of a rapid review approach. Syst Rev 2012; 1:10.

23. Bambra C, Joyce KE, Bellis MA, Greatley A, Greengross S, Hughes S, et al. Reducing health inequalities in priority public health conditions: using rapid review to develop proposals for evidence-based policy. J Public Health (Oxf) 2010; 32:496–505.

24. Greenhalgh T, Peacock R. Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources. Br Med J 2005; 331:1064–1065.

25. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. J Clin Epidemiol 2009; 62:e1–e34.

26. Buscemi N, Hartling L, Vandermeer B, Tjosvold L, Klassen TP. Single data extraction generated more errors than double data extraction in systematic reviews. J Clin Epidemiol 2006; 59:697–703.

27. Berlin JA. Does blinding of readers affect the results of meta-analyses? University of Pennsylvania Meta-analysis Blinding Study Group. Lancet 1997; 350:185–186.

28. Blank MB, Hanrahan NP, Fishbein M, Wu ES, Tennille JA, Ten Have TR, et al. A randomized trial of a nursing intervention for HIV disease management among persons with serious mental illness. Psychiatr Serv 2011; 62:1318–1324.

29. Berg KM, Litwin A, Li X, Heo M, Arnsten JH. Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: a randomized controlled trial. Drug Alcohol Depend 2011; 113:192–199.

30. Chung MH, Richardson BA, Tapia K, Benki-Nugent S, Kiarie JN, Simoni JM, et al. A randomized controlled trial comparing the effects of counseling and alarm device on HAART adherence and virologic outcomes. PLoS Med 2011; 8:e1000422.

31. da Costa TM, Barbosa BJ, Gomes e Costa DA, Sigulem D, de Fatima Marin H, Filho AC, et al. Results of a randomized controlled trial to assess the effects of a mobile SMS-based intervention on treatment adherence in HIV/AIDS-infected Brazilian women and impressions and satisfaction with respect to incoming messages. Int J Med Inform 2012; 81:257–269.

32. de Bruin M, Hospers HJ, van Breukelen GJP, Kok G, Koevoets WM, Prins JM. Electronic monitoring-based counseling to enhance adherence among HIV-infected patients: a randomized controlled trial. 4th ed.2010; United States:American Psychological Association Inc, 421–428.

33. Duncan LG, Moskowitz JT, Neilands TB, Dilworth SE, Hecht FM, Johnson MO. Mindfulness-based stress reduction for HIV treatment side effects: a randomized, wait-list controlled trial. J Pain Symptom Manage 2012; 43:161–171.

34. Fisher JD, Amico KR, Fisher WA, Cornman DH, Shuper PA, Trayling C, et al. Computer-based intervention in HIV clinical care setting improves antiretroviral adherence: the LifeWindows Project. AIDS Behav 2011; 15:1635–1646.

35. Hardy H, Kumar V, Doros G, Farmer E, Drainoni ML, Rybin D, et al. Randomized controlled trial of a personalized cellular phone reminder system to enhance adherence to antiretroviral therapy. AIDS Patient Care STDS 2011; 25:153–161.

36. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885–896.

37. Kalichman SC, Cherry C, Kalichman MO, Amaral CM, White D, Pope H, et al. Integrated behavioral intervention to improve HIV/AIDS treatment adherence and reduce HIV transmission. Am J Public Health 2011; 101:531–538.

38. Kalichman SC, Kalichman MO, Cherry C, Swetzes C, Amaral CM, White D, et al. Brief behavioral self-regulation counseling for HIV treatment adherence delivered by cell phone: an initial test of concept trial. AIDS Patient Care STDS 2011; 25:303–310.

39. Leon A, Caceres C, Fernandez E, Chausa P, Martin M, Codina C, et al. A new multidisciplinary home care telemedicine system to monitor stable chronic human immunodeficiency virus-infected patients: a randomized study. PLoS One 2011. 6.

40. Pyne JM, Fortney JC, Curran GM, Tripathi S, Atkinson JH, Kilbourne AM, et al. Effectiveness of collaborative care for depression in human immunodeficiency virus clinics. Arch Intern Med 2011; 171:23–31.

41. Ramirez-Garcia P, Cote J. An individualized intervention to foster optimal antiretroviral treatment-taking behavior among persons living with HIV: a pilot randomized controlled trial. J Assoc Nurses AIDS Care 2012; 23:220–232.

42. Ruiz I, Olry A, Lopez MA, Prada JL, Causse M. Prospective, randomized, two-arm controlled study to evaluate two interventions to improve adherence to antiretroviral therapy in Spain. 7th ed.2010; Spain:Ediciones Doyma, S.L., Spain, 409–415.

43. Sabin LL, DeSilva MB, Hamer DH, Xu K, Zhang J, Li T, et al. Using electronic drug monitor feedback to improve adherence to antiretroviral therapy among HIV-positive patients in China. AIDS Behav 2010; 14:580–589.

44. 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; 80:404–415.

45. Uzma Q, Emmanuel F, Ather U, Zaman S. Efficacy of interventions for improving antiretroviral therapy adherence in HIV/AIDS cases at PIMS, Islamabad. 6th ed.2011; United States:SAGE Publications Inc, 373–383.

46. Zubaran C, Michelim L, Medeiros G, May W, Foresti K, Madi JM. A randomized controlled trial of a protocol of interviews designed to improve adherence to antiretroviral medications in Southern Brazil. 6th ed.2012; United Kingdom:Royal Society of Medicine Press Ltd, UK, 429–434.

47. DiIorio C, Resnicow K, McDonnell M, Soet J, McCarty F, Yeager K. Using motivational interviewing to promote adherence to antiretroviral medications: a pilot study. J Assoc Nurses AIDS Care 2003; 14:52–62.

48. 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.

49. Fairley CK, Levy R, Rayner CR, Allardice K, Costello K, Thomas C, et al. Randomized trial of an adherence programme for clients with HIV. Int J STD AIDS 2003; 14:805–809.

50. Goujard C, Bernard N, Sohier N, Peyramond D, Lancon F, Chwalow J, et al. Impact of a patient education program on adherence to HIV medication: a randomized clinical trial. J Acquir Immune Defic Syndr 2003; 34:191–194.

51. Lyon ME, Trexler C, Akpan-Townsend C, Pao M, Selden K, Fletcher J, et al. A family group approach to increasing adherence to therapy in HIV-infected youths: results of a pilot project. AIDS Patient Care STDS 2003; 17:299–308.

52. Mann T. Effects of future writing and optimism on health behaviors in HIV-infected women. Ann Behav Med 2001; 23:26–33.

53. Margolin A, Avants SK, Warburton LA, Hawkins KA, Shi J. A randomized clinical trial of a manual-guided risk reduction intervention for HIV-positive injection drug users. Health Psychol 2003; 22:223–228.

54. McPherson-Baker S, Malow RM, Penedo F, Jones DL, Schneiderman N, Klimas NG. Enhancing adherence to combination antiretroviral therapy in nonadherent HIV-positive men. AIDS Care 2000; 12:399–404.

55. Molassiotis A, Lopez-Nahas V, Chung WY, Lam SW. A pilot study of the effects of a behavioural intervention on treatment adherence in HIV-infected patients. AIDS Care 2003; 15:125–135.

56. Murphy DA, Lu MC, Martin D, Hoffman D, Marelich WD. Results of a pilot intervention trial to improve antiretroviral adherence among HIV-positive patients. J Assoc Nurses AIDS Care 2002; 13:57–69.

57. Powell-Cope GM, White J, Henkelman EJ, Turner BJ. Qualitative and quantitative assessments of HAART adherence of substance-abusing women. AIDS Care 2003; 15:239–249.

58. Pradier C, Bentz L, Spire B, Tourette-Turgis C, Morin M, Souville M, et al. Efficacy of an educational and counseling intervention on adherence to highly active antiretroviral therapy: French prospective controlled study. HIV Clin Trials 2003; 4:121–131.

59. Rawlings MK, Thompson MA, Farthing CF, Brown LS, Racine J, Scott RC, et al. Impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients. J Acquir Immune Defic Syndr 2003; 34:174–183.

60. Rigsby MO, Rosen MI, Beauvais JE, Cramer JA, Rainey PM, O’Malley SS, et al. Cue-dose training with monetary reinforcement: pilot study of an antiretroviral adherence intervention. J Gen Intern Med 2000; 15:841–847.

61. Safren SA, Otto MW, Worth JL, Salomon E, Johnson W, Mayer K, et al. Two strategies to increase adherence to HIV antiretroviral medication: life-steps and medication monitoring. Behav Res Ther 2001; 39:1151–1162.

62. Safren SA, Hendriksen ES, Desousa N, Boswell SL, Mayer KH. Use of an on-line pager system to increase adherence to antiretroviral medications. AIDS Care 2003; 15:787–793.

63. Smith SR, Rublein JC, Marcus C, Brock TP, Chesney MA. A medication self-management program to improve adherence to HIV therapy regimens. Patient Educ Couns 2003; 50:187–199.

64. Stenzel MS, McKenzie M, Mitty JA, Flanigan TP. Enhancing adherence to HAART: a pilot program of modified directly observed therapy. AIDS Reader 2001; 11:317–319.

65. Tuldra A, Fumaz CR, Ferrer MJ, Bayes R, Arno A, Balague M, et al. Prospective randomized two-arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000; 25:221–228.

66. Berrien VM, Salazar JC, Reynolds E, McKay K, Group HIVMAI. Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention. AIDS Patient Care Stds 2004; 18:355–363.

67. Bain-Brickley D, Butler LM, Kennedy GE, Rutherford GW. Interventions to improve adherence to antiretroviral therapy in children with HIV infection. Cochrane Database Syst Rev 2011; 12:CD009513.

68. Funck-Brentano I, Dalban C, Veber F, Quartier P, Hefez S, Costagliola D, et al. Evaluation of a peer support group therapy for HIV-infected adolescents. AIDS 2005; 19:1501–1508.

69. Wamalwa DC, Farquhar C, Obimbo EM, Selig S, Mbori-Ngacha DA, Richardson BA, 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.

70. Cantrell RA, Sinkala M, Megazinni K, Lawson-Marriott S, Washington S, Chi BH, et al. A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia. J Acquir Immune Defic Syndr 2008; 49:190–195.

71. Barnighausen T, Chaiyachati K, Chimbindi N, Peoples A, Haberer J, Newell ML. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies. Lancet Infect Dis 2011; 11:942–951.

72. Chang LW, Kagaayi J, Nakigozi G, Ssempijja V, Packer AH, Serwadda D, et al. Effect of peer health workers on AIDS care in Rakai, Uganda: a cluster-randomized trial. PLoS One 2010; 5:e10923.

73. Idoko JA, Agbaji O, Agaba P, Akolo C, Inuwa B, Hassan Z, et al. Direct observation therapy-highly active antiretroviral therapy in a resource-limited setting: the use of community treatment support can be effective. Int J STD AIDS 2007; 18:760–763.

74. Kabore I, Bloem J, Etheredge G, Obiero W, Wanless S, Doykos P, et al. The effect of community-based support services on clinical efficacy and health-related quality of life in HIV/AIDS patients in resource-limited settings in sub-Saharan Africa. AIDS Patient Care STDS 2010; 24:581–594.

75. Lester RT, Ritvo P, Mills EJ, Kariri A, Karanja S, Chung MH, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet 2010; 376:1838–1845.

76. Mugusi F, Mugusi S, Bakari M, Hejdemann B, Josiah R, Janabi M, et al. Enhancing adherence to antiretroviral therapy at the HIV clinic in resource constrained countries; the Tanzanian experience. Trop Med Int Health 2009; 14:1226–1232.

77. Nachega JB, Chaisson RE, Goliath R, Efron A, Chaudhary MA, Ram M, et al. Randomized controlled trial of trained patient-nominated treatment supporters providing partial directly observed antiretroviral therapy. AIDS 2010; 24:1273–1280.

78. Ndekha M, van Oosterhout JJ, Saloojee H, Pettifor J, Manary M. Nutritional status of Malawian adults on antiretroviral therapy 1 year after supplementary feeding in the first 3 months of therapy. Trop Med Int Health 2009; 14:1059–1063.

79. Ndekha MJ, van Oosterhout JJ, Zijlstra EE, Manary M, Saloojee H, Manary MJ. Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial. Br Med J 2009; 338:b1867.

80. Pearson CR, Micek MA, Simoni JM, Hoff PD, Matediana E, Martin DP, 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.

81. Pienaar DH, Myer L, Cleary S, Coetzee D, Michaels D, Cloete K, et al. Models of Care for Antiretroviral Service Delivery. Cape Town:University of Capetown; 2006.

82. Pop-Eleches C, Thirumurthy H, Habyarimana JP, Zivin JG, Goldstein MP, de Walque D, 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; 25:825–834.

83. Roux SM. Diary cards: preliminary evaluation of an intervention tool for improving adherence to antiretroviral therapy and TB preventive therapy in people living with HIV/AIDS [MPH thesis]. University of the Western Cape; 2004.

84. Sarna A, Luchters S, Geibel S, Chersich MF, Munyao P, Kaai S, et al. Short- and long-term efficacy of modified directly observed antiretroviral treatment in Mombasa, Kenya: a randomized trial. J Acquir Immune Defic Syndr 2008; 48:611–619.

85. Sherr KH, Micek MA, Gimbel SO, Gloyd SS, Hughes JP, John-Stewart GC, et al. Quality of HIV care provided by nonphysician clinicians and physicians in Mozambique: a retrospective cohort study. AIDS 2010; 24 (Suppl 1):S59–66.

86. Stubbs BA, Micek MA, Pfeiffer JT, Montoya P, Gloyd S. Treatment partners and adherence to HAART in central Mozambique. AIDS Care 2009; 21:1412–1419.

87. Taiwo BO, Idoko JA, Welty LJ, Otoh I, Job G, Iyaji PG, et al. Assessing the viorologic and adherence benefits of patient-selected HIV treatment partners in a resource-limited setting. J Acquir Immune Defic Syndr 2010; 54:85–92.

88. Thurman TR, Haas LJ, Dushimimana A, Lavin B, Mock N. Evaluation of a case management program for HIV clients in Rwanda. AIDS Care 2010; 22:759–765.

89. Torpey KE, Kabaso ME, Mutale LN, Kamanga MK, Mwango AJ, Simpungwe J, et al. Adherence support workers: a way to address human resource constraints in antiretroviral treatment programs in the public health setting in Zambia. PLoS One 2008; 3:e2204.

90. Antoni MH, Carrico AW, Duran RE, Spitzer S, Penedo F, Ironson G, et al. Randomized clinical trial of cognitive behavioral stress management on human immunodeficiency virus viral load in gay men treated with highly active antiretroviral therapy. Psychosom Med 2006; 68:143–151.

91. Brown JL, Vanable PA. Stress management interventions for HIV-infected individuals: review of recent intervention approaches and directions for future research. 1st ed.2011; New Zealand:DOVE Medical Press Ltd., New Zealand, 95–106.

92. Creswell JD, Myers HF, Cole SW, Irwin MR. Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: a small randomized controlled trial. Brain Behav Immun 2009; 23:184–188.

93. Johnson MO, Dilworth SE, Taylor JM, Neilands TB. Improving coping skills for self-management of treatment side effects can reduce antiretroviral medication nonadherence among people living with HIV. Ann Behav Med 2011; 41:83–91.

94. Weiss SM, Tobin JN, Antoni M, Ironson G, Ishii M, Vaughn A, et al. Enhancing the health of women living with HIV: the SMART/EST Women's Project. Int J Womens Health 2011; 3:63–77.

95. Jaffar S, Amuron B, Foster S, Birungi J, Levin J, Namara G, et al. Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial. Lancet 2009; 374:2080–2089.

96. Wall TL, Sorensen JL, Batki SL, Delucchi KL, London JA, Chesney MA. Adherence to zidovudine (AZT) among HIV-infected methadone patients: a pilot study of supervised therapy and dispensing compared to usual care. Drug Alcohol Depend 1995; 37:261–269.

97. Fogarty L, Roter D, Larson S, Burke J, Gillespie J, Levy R. Patient adherence to HIV medication regimens: a review of published and abstract reports. Patient Educ Couns 2002; 46:93–108.

98. Knobel H, Carmona A, Lopez JL, Gimeno JL, Saballs P, Gonzalez A, et al. [Adherence to very active antiretroviral treatment: impact of individualized assessment]. Enferm Infecc Microbiol Clin 1999; 17:78–81.

99. Altice FL, Maru DS, Bruce RD, Springer SA, Friedland GH. Superiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: a prospective, randomized, controlled trial. Clin Infect Dis 2007; 45:770–778.

100. Maru DS, Bruce RD, Walton M, Springer SA, Altice FL. Persistence of virological benefits following directly administered antiretroviral therapy among drug users: results from a randomized controlled trial. J Acquir Immune Defic Syndr 2009; 50:176–181.

101. Hart JE, Jeon CY, Ivers LC, Behforouz HL, Caldas A, Drobac PC, et al. Effect of directly observed therapy for highly active antiretroviral therapy on virologic, immunologic, and adherence outcomes: a meta-analysis and systematic review. J Acquir Immune Defic Syndr 2010; 54:167–179.

102. Gross R, Tierney C, Andrade A, Lalama C, Rosenkranz S, Eshleman SH, et al. Modified directly observed antiretroviral therapy compared with self-administered therapy in treatment-naive HIV-1-infected patients: a randomized trial. Arch Intern Med 2009; 169:1224–1232.

103. Lucas GM, Mullen BA, Weidle PJ, Hader S, McCaul ME, Moore RD. Directly administered antiretroviral therapy in methadone clinics is associated with improved HIV treatment outcomes, compared with outcomes among concurrent comparison groups. Clin Infect Dis 2006; 42:1628–1635.

104. Macalino GE, Hogan JW, Mitty JA, Bazerman LB, Delong AK, Loewenthal H, et al. A randomized clinical trial of community-based directly observed therapy as an adherence intervention for HAART among substance users. AIDS 2007; 21:1473–1477.

105. Munoz M, Finnegan K, Zeladita J, Caldas A, Sanchez E, Callacna M, et al. Community-based DOT-HAART accompaniment in an urban resource-poor setting. AIDS Behav 2010; 14:721–730.

106. Tinoco I, Giron-Gonzalez JA, Gonzalez-Gonzalez MT, Vergara de Campos A, Rodriguez-Felix L, Serrano A, et al. Efficacy of directly observed treatment of HIV infection: experience in AIDS welfare homes. Eur J Clin Microbiol Infect Dis 2004; 23:331–335.

107. Wohl AR, Garland WH, Valencia R, Squires K, Witt MD, Kovacs A, et al. A randomized trial of directly administered antiretroviral therapy and adherence case management intervention. Clin Infect Dis 2006; 42:1619–1627.

108. Andrade AS, McGruder HF, Wu AW, Celano SA, Skolasky RL Jr, Selnes OA, et al. A programmable prompting device improves adherence to highly active antiretroviral therapy in HIV-infected subjects with memory impairment. Clin Infect Dis 2005; 41:875–882.

109. Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2008; 2:CD000011.

110. Collier AC, Ribaudo H, Mukherjee AL, Feinberg J, Fischl MA, Chesney M. A randomized study of serial telephone call support to increase adherence and thereby improve virologic outcome in persons initiating antiretroviral therapy. J Infect Dis 2005; 192:1398–1406.

111. Remien RH, Stirratt MJ, Dolezal C, Dognin JS, Wagner GJ, Carballo-Dieguez A, et al. Couple-focused support to improve HIV medication adherence: a randomized controlled trial. AIDS 2005; 19:807–814.

112. Samet JH, Horton NJ, Meli S, Dukes K, Tripps T, Sullivan L, et al. A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems. Antivir Ther 2005; 10:83–93.

113. van Servellen G, Nyamathi A, Carpio F, Pearce D, Garcia-Teague L, Herrera G, et al. Effects of a treatment adherence enhancement program on health literacy, patient-provider relationships, and adherence to HAART among low-income HIV-positive Spanish-speaking Latinos. AIDS Patient Care STDS 2005; 19:745–759.

114. Weber R, Christen L, Christen S, Tschopp S, Znoj H, Schneider C, et al. Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antivir Ther 2004; 9:85–95.

115. DiIorio C, Mccarty F, Resnicow K, Holstad MM, Soet J, Yeager K, et al. Using motivational interviewing to promote adherence to antiretroviral medications: a randomized controlled study. AIDS Care 2008; 20:273–283.

116. Hill S, Kavookjian J. Motivational interviewing as a behavioral intervention to increase HAART adherence in patients who are HIV-positive: a systematic review of the literature. AIDS Care 2012; 24:583–592.

117. Parsons JT, Golub SA, Rosof E, Holder C. Motivational interviewing and cognitive-behavioral intervention to improve HIV medication adherence among hazardous drinkers: a randomized controlled trial. J Acquir Immune Defic Syndr 2007; 46:443–450.

118. Mitty JA, Macalino GE, Bazerman LB, Loewenthal HG, Hogan JW, MacLeod CJ, et al. The use of community-based modified directly observed therapy for the treatment of HIV-infected persons. J Acquir Immune Defic Syndr 2005; 39:545–550.

119. Kenya S, Chida N, Symes S, Shor-Posner G. Can community health workers improve adherence to highly active antiretroviral therapy in the USA? A review of the literature. HIV Med 2011; 12:525–534.

120. Purcell DW, Latka MH, Metsch LR, Latkin CA, Gomez CA, Mizuno Y, et al. Results from a randomized controlled trial of a peer-mentoring intervention to reduce HIV transmission and increase access to care and adherence to HIV medications among HIV-seropositive injection drug users. J Acquir Immune Defic Syndr 2007; 46 (Suppl 2):S35–47.

121. Simoni JM, Pantalone DW, Plummer MD, Huang B. A randomized controlled trial of a peer support intervention targeting antiretroviral medication adherence and depressive symptomatology in HIV-positive men and women. Health Psychol 2007; 26:488–495.

122. Visnegarwala F, Rodriguez-Barradass MC, Graviss EA, Caprio M, Nykyforchyn M, Laufman L. Community outreach with weekly delivery of antiretroviral drugs compared to cognitive-behavioural healthcare team-based approach to improve adherence among indigent women newly starting HAART. AIDS Care 2006; 18:332–338.

123. Williams AB, Fennie KP, Bova CA, Burgess JD, Danvers KA, Dieckhaus KD. Home visits to improve adherence to highly active antiretroviral therapy: a randomized controlled trial. J Acquir Immune Defic Syndr 2006; 42:314–321.

124. Golin CE, Earp J, Tien HC, Stewart P, Porter C, Howie L. A 2-arm, randomized, controlled trial of a motivational interviewing-based intervention to improve adherence to antiretroviral therapy (ART) among patients failing or initiating ART. J Acquir Immune Defic Syndr 2006; 42:42–51.

125. Leeman J, Chang YK, Lee EJ, Voils CI, Crandell J, Sandelowski M. Implementation of antiretroviral therapy adherence interventions: a realist synthesis of evidence. J Adv Nurs 2010; 66:1915–1930.

126. Harwell JI, Flanigan TP, Mitty JA, Macalino GE, Caliendo AM, Ingersoll J, et al. Directly observed antiretroviral therapy to reduce genital tract and plasma HIV-1 RNA in women with poor adherence. AIDS 2003; 17:1990–1993.

127. Holzemer WL, Bakken S, Portillo CJ, Grimes R, Welch J, Wantland D, et al. Testing a nurse-tailored HIV medication adherence intervention. Nurs Res 2006; 55:189–197.

128. Javanbakht M, Prosser P, Grimes T, Weinstein M, Farthing C. Efficacy of an individualized adherence support program with contingent reinforcement among nonadherent HIV-positive patients: results from a randomized trial. J Int Assoc Phys AIDS Care (Chic) 2006; 5:143–150.

129. Johnson MO, Charlebois E, Morin SF, Remien RH, Chesney MA. Effects of a behavioral intervention on antiretroviral medication adherence among people living with HIV: the healthy living project randomized controlled study. J Acquir Immune Defic Syndr 2007; 46:574–580.

130. Jones DL, McPherson-Baker S, Lydston D, Camille J, Brondolo E, Tobin JN, et al. Efficacy of a group medication adherence intervention among HIV positive women: the SMART/EST Women's Project. AIDS Behav 2007; 11:79–86.

131. Koenig LJ, Pals SL, Bush T, Pratt Palmore M, Stratford D, Ellerbrock TV. Randomized controlled trial of an intervention to prevent adherence failure among HIV-infected patients initiating antiretroviral therapy. Health Psychol 2008; 27:159–169.

132. Levin TR, Klibanov OM, Axelrod P, Finley GL, Gray A, Holdsworth C, et al. A randomized trial of educational materials, pillboxes, and mailings to improve adherence with antiretroviral therapy in an inner city HIV clinic. J Clin Outcomes Manag 2006; 13:217–221.

133. Ma M, Brown BR, Coleman M, Kibler JL, Loewenthal H, Mitty JA. The feasibility of modified directly observed therapy for HIV-seropositive African American substance users. AIDS Patient Care STDS 2008; 22:139–146.

134. Milam J, Richardson JL, McCutchan A, Stoyanoff S, Weiss J, Kemper C, et al. Effect of a brief antiretroviral adherence intervention delivered by HIV care providers. J Acquir Immune Defic Syndr 2005; 40:356–363.

135. Parsons JT, Rosof E, Punzalan JC, Di Maria L. Integration of motivational interviewing and cognitive behavioral therapy to improve HIV medication adherence and reduce substance use among HIV-positive men and women: results of a pilot project. AIDS Patient Care STDS 2005; 19:31–39.

136. Reynolds NR, Testa MA, Su M, Chesney MA, Neidig JL, Frank I, et al. Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial. J Acquir Immune Defic Syndr 2008; 47:62–68.

137. Rosen MI, Dieckhaus K, McMahon TJ, Valdes B, Petry NM, Cramer J, et al. Improved adherence with contingency management. AIDS Patient Care STDS 2007; 21:30–40.

138. Sorensen JL, Haug NA, Delucchi KL, Gruber V, Kletter E, Batki SL, et al. Voucher reinforcement improves medication adherence in HIV-positive methadone patients: a randomized trial. Drug Alcohol Depend 2007; 88:54–63.

139. Wagner GJ, Kanouse DE, Golinelli D, Miller LG, Daar ES, Witt MD, et al. Cognitive-behavioral intervention to enhance adherence to antiretroviral therapy: a randomized controlled trial (CCTG 578). AIDS 2006; 20:1295–1302.

140. Jones DL, Ishii M, LaPerriere A, Stanley H, Antoni M, Ironson G, et al. Influencing medication adherence among women with AIDS. AIDS Care 2003; 15:463–474.

141. Manias E, Williams A. Medication adherence in people of culturally and linguistically diverse backgrounds: a meta-analysis. Ann Pharmacother 2010; 44:964–982.

142. Rathbun RC, Farmer KC, Stephens JR, Lockhart SM. Impact of an adherence clinic on behavioral outcomes and virologic response in treatment of HIV infection: a prospective, randomized, controlled pilot study. Clin Ther 2005; 27:199–209.

143. van Servellen G, Carpio F, Lopez M, Garcia-Teague L, Herrera G, Monterrosa F, et al. Program to enhance health literacy and treatment adherence in low-income HIV-infected Latino men and women. AIDS Patient Care STDS 2003; 17:581–594.

144. Wyatt GE, Longshore D, Chin D, Carmona JV, Loeb TB, Myers HF, et al. The efficacy of an integrated risk reduction intervention for HIV-positive women with child sexual abuse histories. AIDS Behav 2004; 8:453–462.

145. Levy RW, Rayner CR, Fairley CK, Kong DC, Mijch A, Costello K, et al. Multidisciplinary HIV adherence intervention: a randomized study. AIDS Patient Care STDS 2004; 18:728–735.

146. Mannheimer SB, Morse E, Matts JP, Andrews L, Child C, Schmetter B, et al. Sustained benefit from a long-term antiretroviral adherence intervention. Results of a large randomized clinical trial. J Acquir Immune Defic Syndr 2006; 43 (Suppl 1):S41–47.

147. Saberi P, Johnson MO. Technology-based self-care methods of improving antiretroviral adherence: a systematic review. PLoS One 2011. 6.

148. Murphy DA, Marelich WD, Rappaport NB, Hoffman D, Farthing C. Results of an antiretroviral adherence intervention: STAR (Staying Healthy: Taking Antiretrovirals Regularly). J Int Assoc Physicians AIDS Care (Chic) 2007; 6:113–124.

149. Simoni JM, Huh D, Frick PA, Pearson CR, Andrasik MP, Dunbar PJ, et al. Peer support and pager messaging to promote antiretroviral modifying therapy in Seattle: a randomized controlled trial. J Acquir Immune Defic Syndr 2009; 52:465–473.

150. Simoni JM, Chen WT, Huh D, Fredriksen-Goldsen KI, Pearson C, Zhao H, et al. A preliminary randomized controlled trial of a nurse-delivered medication adherence intervention among HIV-positive outpatients initiating antiretroviral therapy in Beijing, China. AIDS Behav 2011; 15:919–929.

151. Wu AW, Snyder CF, Huang IC, Skolasky R, McGruder HF, Celano SA, et al. A randomized trial of the impact of a programmable medication reminder device on quality of life in patients with AIDS. AIDS Patient Care STDS 2006; 20:773–781.

152. Frick P, Tapia K, Grant P, Novotny M, Kerzee J. The effect of a multidisciplinary program on HAART adherence. AIDS Patient Care STDS 2006; 20:511–524.

153. Saberi P, Dong BJ, Johnson MO, Greenblatt RM, Cocohoba JM. The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review. Patient Prefer Adherence 2012; 6:297–322.

154. Hirsch JD, Gonzales M, Rosenquist A, Miller TA, Gilmer TP, Best BM. Antiretroviral therapy adherence, medication use, and healthcare costs during 3 years of a community pharmacy medication therapy management program for Medi-Cal beneficiaries with HIV/AIDS. J Manag Care Pharm 2011; 17:213–223.

155. Horberg MA, Hurley LB, Silverberg MJ, Kinsman CJ, Quesenberry CP. Effect of clinical pharmacists on utilization of and clinical response to antiretroviral therapy. J Acquir Immune Defic Syndr 2007; 44:531–539.

156. March K, Mak M, Louie SG. Effects of pharmacists’ interventions on patient outcomes in an HIV primary care clinic. Am J Health Syst Pharm 2007; 64:2574–2578.

157. Pirkle CM, Boileau C, Nguyen VK, Machouf N, Ag-Aboubacrine S, Niamba PA, et al. Impact of a modified directly administered antiretroviral treatment intervention on virological outcome in HIV-infected patients treated in Burkina Faso and Mali. HIV Med 2009; 10:152–156.

158. Rotheram-Borus MJ, Swendeman D, Comulada WS, Weiss RE, Lee M, Lightfoot M. Prevention for substance-using HIV-positive young people: telephone and in-person delivery. J Acquir Immune Defic Syndr 2004; 37 (Suppl 2):S68–77.

159. Simoni JM, Pearson CR, Pantalone DW, Marks G, Crepaz N. 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 2006; 43:S23–S35.

160. Byron E, Gillespie S, Nangami M. Integrating nutrition security with treatment of people living with HIV: lessons from Kenya. Food Nutr Bull 2008; 29:87–97.

161. Tirivayi N, Groot W. Health and welfare effects of integrating AIDS treatment with food assistance in resource constrained settings: a systematic review of theory and evidence. Soc Sci Med 2011; 73:685–692.

162. Feaster DJ, Mitrani VB, Burns MJ, McCabe BE, Brincks AM, Rodriguez AE, et al. A randomized controlled trial of structural ecosystems therapy for HIV medication adherence and substance abuse relapse prevention. Drug Alcohol Depend 2010; 111:227–234.

163. Wechsberg WM, Golin C, El-Bassel N, Hopkins J, Zule W. Current interventions to reduce sexual risk behaviors and crack cocaine use among HIV-infected individuals. Curr HIV/AIDS Rep 2012.

164. Ingersoll KS, Farrell-Carnahan L, Cohen-Filipic J, Heckman CJ, Ceperich SD, Hettema J, et al. A pilot randomized clinical trial of two medication adherence and drug use interventions for HIV+ crack cocaine users. Drug Alcohol Depend 2011; 116:177–187.

165. Page J, Weber R, Somaini B, Nostlinger C, Donath K, Jaccard R. Quality of generalist vs. specialty care for people with HIV on antiretroviral treatment: a prospective cohort study. HIV Med 2003; 4:276–286.

166. Wong WC, Luk CW, Kidd MR. Is there a role for primary care clinicians in providing shared care in HIV treatment? A systematic literature review. Sex Transm Infect 2012; 88:125–131.

167. Igumbor JO, Scheepers E, Ebrahim R, Jason A, Grimwood A. An evaluation of the impact of a community-based adherence support programme on ART outcomes in selected government HIV treatment sites in South Africa. AIDS Care 2011; 23:231–236.

168. Wouters E, Van Damme W, van Rensburg D, Masquillier C, Meulemans H. Impact of community-based support services on antiretroviral treatment programme delivery and outcomes in resource-limited countries: a synthetic review. BMC Health Serv Res 2012; 12:194.

169. Kunutsor S, Walley J, Katabira E, Muchuro S, Balidawa H, Namagala E, et al. Improving clinic attendance and adherence to antiretroviral therapy through a treatment supporter intervention in Uganda: a randomized controlled trial. AIDS Behav 2011; 15:1795–1802.

170. Rich ML, Miller AC, Niyigena P, Franke MF, Niyonzima JB, Socci A, et al. Excellent clinical outcomes and high retention in care among adults in a community-based HIV treatment program in rural Rwanda. J Acquir Immune Defic Syndr 2012; 59:e35–e42.

171. Bangsberg DR, Mills EJ. Long-term adherence to antiretroviral therapy in resource-limited settings: a bitter pill to swallow. Antivir Ther 2013; 18:25–28.

172. Mills EJ, Lester R, Ford N. Promoting long term adherence to antiretroviral treatment. Br Med J 2012; 344:e4173.

173. Bastard M, Fall MB, Laniece I, Taverne B, Desclaux A, Ecochard R, et al. Revisiting long-term adherence to highly active antiretroviral therapy in Senegal using latent class analysis. J Acquir Immune Defic Syndr 2011; 57:55–61.

174. Cambiano V, Lampe FC, Rodger AJ, Smith CJ, Geretti AM, Lodwick RK, et al. Long-term trends in adherence to antiretroviral therapy from start of HAART. AIDS 2010; 24:1153–1162.

175. Chaiyachati K, Hirschhorn LR, Tanser F, Newell ML, Barnighausen T. Validating five questions of antiretroviral nonadherence in a public-sector treatment program in rural South Africa. AIDS Patient Care STDS 2011; 25:163–170.

176. Bärnighausen T, Salomon JA, Sangrujee N. HIV treatment as prevention: issues in economic evaluation. PLoS Med 2012; 9:e1001263.

177. Flexner C, Plumley B, Brown Ripin D. Treatment optimization: an outline for future success. Curr Opin HIV AIDS 2013; 8:523–527.

178. Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference?. Curr Med Res Opin 2014; 30:89–97.

179. 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 Infectious Dis 2014; [Epub].


antiretroviral adherence, interventions, randomized controlled trials, systematic review

Supplemental Digital Content

Back to Top | Article Outline

© 2014 Lippincott Williams & Wilkins, Inc.


Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.