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Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators
Global Health Sciences Literature Digest
Published January 30, 2007
Journal Article

Mills EJ, Nachega JB, Bangsberg DR, Singh S, Rachlis B, Wu P, Wilson K, Buchan I, Gill CJ, Cooper C. Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators. PLoS Med. 2006 Nov;3(11):e438.


To perform a review of studies from both developed and developing countries in order to identify barriers to and facilitating factors of antiretroviral adherence, as reported by patients.

Search Strategy

Studies from both developed and developing countries were included. Eligible studies met the following criteria: 1) they were based on an original research study; 2) they contained content addressing barriers or facilitators to antiretroviral adherence; and 3) were either qualitative studies or quantitative surveys.

A systematic, all-language literature search was performed on publications prior to June 2005. The following databases were searched: AMED, Campbell Collaboration, CINAHL, Cochrane Library, EMBASE, ERIC, MedLine, and NHS EED. Unpublished studies were identified by applying the search terms to:; the UK National Research Register; conference abstracts from meetings of the International AIDS Society (IAS) and Conference on Retroviruses and Opportunistic Infections (CROI). Search terms included "compliance OR adherence," "HIV" or "AIDS," "factors OR determinant* OR barriers," "motivate* OR facilit*," and "HAART OR antiretroviral." The search was supplemented by reviewing the bibliographies of key papers.


228 studies were initially identified, of which 84 met inclusion criteria and were included in the analysis. Thirty-seven studies were qualitative, of which 12 were based on focus groups, 15 on semi-structured interviews, and nine on open-ended interviews. The 47 remaining studies were based on quantitative surveys. Seventy-two studies were conducted in developed countries, and 12 in resource-poor regions.


A total of 1,846 participants were included in the analysis; 39% were women and 62% were men. No summary of populations from which study samples were drawn was provided.

Outcome Measures

The outcome measures were based on themes identified from the review of qualitative studies, and described self-identified barriers and facilitators to adherence grouped as: 1) patient-related factors; 2) beliefs about medication; 3) daily schedules; and 4) interpersonal factors/relationships. Quantitative surveys were evaluated individually, and a meta-analysis was performed to determine the frequency with which identified themes were evaluated and reported. Data on the quality of both qualitative and quantitative studies were extracted, using pre-determined criteria.(1)


Common barriers reported in both developed and developing countries included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions about treatment, overly complicated regimens, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Barriers frequently reported by persons from resource-poor countries were issues of access, including financial constraints and a disruption in medication availability. Important facilitators reported by patients in developed countries included having a sense of self-worth, witnessing the positive effects of ART, acceptance of HIV sero-status, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. No facilitators of adherence were discussed in any study from a developing country.

The primary deficiencies identified among qualitative studies were the lack of trained facilitators and of response clarification. The vast majority of the quantitative surveys failed to involve the population in development of the survey, and in random sampling was used in only four studies (although it is not clear whether sampling was otherwise representative).


The authors found that important barriers to adherence are consistent across multiple settings and countries. Research is still needed to determine factors that support adherence in developing countries. Clinicians should use this information to engage in open discussion with patients, in order to promote adherence and identify barriers and facilitators within their own populations.

Quality Rating

Based on the QUOROM grading system for systematic reviews, this study is of adequate to high quality. This review was limited by the following: potential reporting bias of original reports; detailed population descriptions not provided; and large heterogeneity in pooled survey data. The review did not appear to include adherence intervention studies, though it was not clear if this was because there were none available, or because only surveys were to be included.

In Context

This is the first systematic review of studies examining concerns of HIV patients in maintaining their own ART adherence. This review is unique in that it include qualitative studies, based on the previous demonstration by the authors that systematic evaluation of qualitative studies can improve content validity of surveys.(1,2)

The authors applied specific criteria to determine the quality of the studies reviewed, and listed these individually for each study. Because the primary outcome was the identification and listing of themes, this paper did not attempt to identify or systematically evaluate studies that measured the association between these self-reported concerns and specific measures of adherence. Adherence intervention studies may have provided additional important data. The article by Mannheimer et al, reviewed in this issue,(3) suggests that self-report of concerns (such as "forgetting to take medications") may not necessarily represent the actual barrier to adherence.

Programmatic Implications

Only 12 of the studies included in this analysis were from resource poor-countries, highlighting the fact that rigorous studies of antiretroviral adherence still need to be conducted. Interestingly, available research from developing countries has focused on barriers, rather than on factors that might improve adherence. Nevertheless, one of the recurrent themes from resource-poor regions is the importance of logistical and economic factors, including the ability of patients to access care, and availability of a regular supply of medication.


  1. Mills E, Jadad AR, Ross C, et al. Systematic review of qualitative studies exploring parental beliefs and attitudes toward childhood vaccination identifies common barriers to vaccination. J Clin Epidemiol 2005 Nov;58(11):1081-8.
  2. Mills EJ, Montori VM, Ross CP, et al. Systematically reviewing qualitative studies complements survey design: an exploratory study of barriers to paediatric immunisations. J Clin Epidemiol 2005 Nov;58(11):1101-8.
  3. Mannheimer SB, Morse E, Matts JP, et al. Sustained benefit from a long-term antiretroviral adherence intervention: results of a large randomized clinical trial. J Acquir Immune Defic Syndr 2006 Dec 1;43 Suppl 1:S41-S47.