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      Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators

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          Abstract

          Background

          Adherence to highly active antiretroviral therapy (HAART) medication is the greatest patient-enabled predictor of treatment success and mortality for those who have access to drugs. We systematically reviewed the literature to determine patient-reported barriers and facilitators to adhering to antiretroviral therapy.

          Methods and Findings

          We examined both developed and developing nations. We searched the following databases: AMED (inception to June 2005), Campbell Collaboration (inception to June 2005), CinAhl (inception to June 2005), Cochrane Library (inception to June 2005), Embase (inception to June 2005), ERIC (inception to June 2005), MedLine (inception to June 2005), and NHS EED (inception to June 2005). We retrieved studies conducted in both developed and developing nation settings that examined barriers and facilitators addressing adherence. Both qualitative and quantitative studies were included. We independently, in duplicate, extracted data reported in qualitative studies addressing adherence. We then examined all quantitative studies addressing barriers and facilitators noted from the qualitative studies. In order to place the findings of the qualitative studies in a generalizable context, we meta-analyzed the surveys to determine a best estimate of the overall prevalence of issues. We included 37 qualitative studies and 47 studies using a quantitative methodology (surveys). Seventy-two studies (35 qualitative) were conducted in developed nations, while the remaining 12 (two qualitative) were conducted in developing nations. Important barriers reported in both economic settings included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions of treatment, regimens that are too complicated, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Important facilitators reported by patients in developed nation settings included having a sense of self-worth, seeing positive effects of antiretrovirals, accepting their seropositivity, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. Among 37 separate meta-analyses examining the generalizability of these findings, we found large heterogeneity.

          Conclusions

          We found that important barriers to adherence are consistent across multiple settings and countries. Research is urgently needed to determine patient-important factors for adherence in developing world settings. Clinicians should use this information to engage in open discussion with patients to promote adherence and identify barriers and facilitators within their own populations.

          Abstract

          An analysis of qualitative and quantitative studies found consistent barriers to adherence to HIV therapy across multiple settings and countries, ranging from access to medication to problems with complicated regimens.

          Editors' Summary

          Background.

          The World Health Organization has estimated that in 2005, about 38 million people worldwide were living with HIV/AIDS; the mortality caused by HIV/AIDS is very high. Antiretroviral drugs are effective at controlling the disease and extending life span. However, it is important for people to stick to the drug regimens exactly in order to keep levels of HIV low, prevent it from becoming resistant to drugs, and stop the illness from progressing. However, many people find it very difficult to take antiretroviral drugs precisely as they should. There is already some evidence from research studies on the reasons why this is the case. There are two different research approaches taken by these studies: “qualitative” methods, which try to find out about attitudes and behaviors using focus groups, interviews, or other techniques; and “quantitative” methods, which try to find out about peoples' opinions and experience using surveys with set questions for the participants to answer, and then count the different responses.

          Why Was This Study Done?

          The investigators wanted to put together all of the available evidence from published research studies (called doing a “systematic review”) on which factors affected people's adherence to antiretroviral drugs. They wanted to do a systematic review because it is thought to be a very rigorous way of appraising all the available evidence (although there is considerable debate about the value of using such a method to analyze the results of qualitative research).

          What Did the Researchers Do and Find?

          The study team searched biomedical literature databases as well as conference abstracts and research registries using a defined set of search queries. They screened all the scientific papers they found; those reporting results of original research into factors affecting antiretroviral adherence were then analyzed in more detail. 84 relevant studies were identified, of which 37 used “qualitative” methods (focus groups, interviews, open-ended questioning) and 47 used “quantitative” methods (surveys). Most of these studies had been carried out in the developed world. Then, the researchers extracted the factors affecting adherence from the original studies, which could be either “positive” factors (helping adherence) or “negative” ones (making adherence more difficult). They classified the factors into four key themes: “patient related” (e.g., seeing positive results, fear of disclosure, being depressed); “beliefs about medication” (e.g., faith in how well the drugs worked, side effects); “daily schedules” (e.g., using reminder tools, disruptions to routine); and “interpersonal relationships” (e.g., trusting relations with health-care provider; social isolation).

            Many barriers to adherence were common to both developed and developing settings. Some factors were unique to the studies conducted in the developing world, such as financial constraints and problems with traveling to get access to treatment. Fear of disclosure was an important barrier identified in many of the studies.

          What Do These Findings Mean?

          The researchers combined the results of many different studies and identified factors that help or obstruct adherence to antiretroviral treatment. By identifying influences common to the different settings, greater weight can be placed on the factors that were identified. Only 12 of the studies included in this research were from the developing world, where the majority of HIV/AIDS patients live; hence more work is needed to examine and address the factors influencing antiretroviral adherence in these parts of the world. This study provides researchers and health policy makers with a starting point for changes that might help to ensure greater adherence to antiretroviral treatment.

          Additional Information.

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030438.

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          Most cited references96

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          Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors.

          Enrolling participants onto clinical trials of cancer presents an important challenge. We aimed to identify the concerns of patients with cancer about, and the barriers to, participation in clinical trials. We did a systematic review to assess studies of barriers to participation in experimental trials and randomised trials for validity and content. We estimated the frequency with which patients identified particular issues by pooling across studies that presented data for barriers to participation in clinical trials as proportions. We analysed 12 qualitative studies (n=722) and 21 quantitative studies (n=5452). Two qualitative studies inquired of patients who were currently enrolled onto clinical trials, and ten inquired of patients who were eligible for enrolment onto various clinical trials. Barriers to participation in clinical trials were protocol-related, patient-related, or physician-related. The most common reasons cited as barriers included: concerns with the trial setting; a dislike of randomisation; general discomfort with the research process; complexity and stringency of the protocol; presence of a placebo or no-treatment group; potential side-effects; being unaware of trial opportunities; the idea that clinical trials are not appropriate for serious diseases; fear that trial involvement would have a negative effect on the relationship with their physician; and their physician's attitudes towards the trial. Meta-analysis confirmed the findings of our systematic review. The identification of such barriers to the participation in clinical trials should help trialists to develop strategies that will keep to a maximum participation and cooperation in cancer trials, while informing and protecting prospective participants adequately.
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            Non-adherence to highly active antiretroviral therapy predicts progression to AIDS.

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              The statistical basis of meta-analysis.

              Two models for study-to-study variation in a meta-analysis are presented, critiqued and illustrated. One, the fixed effects model, takes the studies being analysed as the universe of interest; the other, the random effects model, takes these studies as representing a sample from a larger population of possible studies. With emphasis on clinical trials, this paper illustrates in some detail the application of both models to three summary measures of the effect of an experimental intervention versus a control: the standardized difference for comparing two means, and the relative risk and odds ratio for comparing two proportions.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                pmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                November 2006
                21 November 2006
                : 3
                : 11
                : e438
                Affiliations
                [1 ]Centre for International Health and Human Rights Studies, Toronto, Ontario, Canada
                [2 ]Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [3 ]San Francisco General Hospital, AIDS Division, University of California San Francisco, San Francisco, California, United States of America
                [4 ]BC Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, British Columbia, Canada
                [5 ]Canadian College of Naturopathic Medicine, North York, Ontario, Canada
                [6 ]Department of Medicine, University of Toronto, Toronto, Ontario, Canada
                [7 ]Evidence for Population Health Unit, University of Manchester, Manchester, United Kingdom
                [8 ]Center for International Health and Development, Boston University School of Public Health, Boston, Massachusetts, United States of America
                [9 ]Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
                University of Ottawa, Ottawa, Ontario, Canada
                Author notes
                * To whom correspondence should be addressed. E-mail: millsej@ 123456univmail.cis.mcmaster.ca
                Article
                05-PLME-RA-0713R3 plme-03-11-08
                10.1371/journal.pmed.0030438
                1637123
                17121449
                86dc48be-170e-4d5e-a05c-0e4ebc61bf73
                Copyright: © 2006 Mills et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 8 December 2005
                : 4 September 2006
                Page count
                Pages: 26
                Categories
                Research Article
                Infectious Diseases
                Science Policy
                HIV/AIDS
                Statistics
                HIV Infection/AIDS
                Resource Allocation and Rationing
                Custom metadata
                Mills EJ, Nachega JB, Bangsberg DR, Singh S, Rachlis B, et al. (2006) Adherence to HAART: A systematic review of developed and developing nation patient-reported barriers and facilitators. PLoS Med 3(11): e438. doi: 10.1371/journal.pmed.0030438

                Medicine
                Medicine

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