Factors influencing adherence to antiretroviral treatment in Asian developing countries: a systematic review

Authors


Corresponding Author Sharada P. Wasti, Section of Public health (ScHARR), University of Sheffield, Sheffield, S1 4DA, UK. Tel.: +44 (0) 1142 226 389; Fax: +44 (0) 1142 724 095; E-mails: s.wasti@sheffield.ac.uk; Spwasti@gmail.com

Abstract

Objective  To systematically review the literature of factors affecting adherence to Antiretroviral treatment (ART) in Asian developing countries.

Methods  Database searches in Medline/Ovid, Cochrane library, CINAHL, Scopus and PsychINFO for studies published between 1996 and December 2010. The reference lists of included papers were also checked, with citation searching on key papers.

Results  A total of 437 studies were identified, and 18 articles met the inclusion criteria and were extracted and critically appraised, representing in 12 quantitative, four qualitative and two mixed-method studies. Twenty-two individual themes, including financial difficulties, side effects, access, stigma and discrimination, simply forgetting and being too busy, impeded adherence to ART, and 11 themes, including family support, self-efficacy and desire to live longer, facilitated adherence.

Conclusion  Adherence to ART varies between individuals and over time. We need to redress impeding factors while promoting factors that reinforce adherence through financial support, better accessible points for medicine refills, consulting doctors for help with side effects, social support and trusting relationships with care providers.

Abstract

Objectif:  Examiner systématiquement la littérature sur les facteurs influençant l’adhésion au traitement ARV (TARV) dans les pays asiatiques en développement.

Méthodes:  Recherche dans les bases de données Medline/Ovid, Cochrane Library, CINAHL, Scopus et PsychINFO pour des études publiées entre 1996 et décembre 2010. Les listes de références des articles cités ont également été vérifiées, avec la recherche des citations d’articles clés.

Résultats:  Au total 437 études ont été identifiées, 18 articles ont répondu aux critères d’inclusion et ont été extraits et évalués de façon critique, ce qui représente 12 études quantitatives, 4 qualitatives et 2 à méthodes mixtes. 31 thèmes différents comprenant les difficultés financières, les effets secondaires, l’accès, la stigmatisation et la discrimination, le simple oubli et le fait d’être trop occupé, entravaient l’adhésion au TARV, et 11 thèmes comprenant le soutien familial, l’auto-efficacité et le désir de vivre plus longtemps, facilitaient l’adhésion.

Conclusion:  L’adhésion au TARV varie selon les individus et dans le temps. Il est nécessaire d’abaisser les facteurs entravant l’adhésion tout en favorisant ceux la renforçant, à travers un soutien financier, de meilleurs points d’accès pour la collecte des médicaments, des médecins-conseil pour les effets secondaires, un soutien social et des relations de confiance avec les prestataires de soins.

Abstract

Objetivo:  Revisión sistemática en la literatura de los factores que afectan la adherencia al TAR en países asiáticos en vías de desarrollo.

Métodos:  Búsquedas en las bases de datos de Medline/Ovid, Cochrane, CINAHL, Scopus y PsychINFO de estudios publicados entre 1996 y Diciembre del 2010. Las listas de referencia de los artículos incluídos también fueron revisadas, y mediante el índice de citación se eligieron los artículos claves.

Resultados:  Se identificó un total de 437 estudios, y 18 artículos cumplían los criterios de inclusión y fueron extraídos y valorados críticamente, representando a 12 estudios con metodología cuantitativa, 4 cualitativos y 2 con metodología mixta. 31 razones individuales impedían la adherencia al TAR, incluyendo las dificultades financieras, efectos secundarios, acceso, estigma y discriminación, simplemente el olvidarse o el estar demasiado ocupado y 11 motivos facilitaban la adherencia, incluyendo el apoyo familiar, la auto-eficacia, y el deseo de vivir más tiempo.

Conclusión:  La adherencia al TAR varía entre individuos y a lo largo del tiempo. Necesitamos reparar los factores negativos al tiempo que promovemos aquellos factores que refuerzan la adherencia mediante el apoyo financiero, un mejor acceso a los puntos de entrega de los medicamentos, médicos de consulta que ayuden los efectos secundarios y confianza en la relación con los proveedores.

Introduction

Antiretroviral treatment (ART) provides relief to HIV-infected individuals by reducing the likelihood of opportunistic infections rather than curing the disease. Since 1996, the introduction of ART has greatly improved the life span and quality of life for people living with HIV (PLWH) (Amico et al. 2005). Better ART has led to a reduction in disease progression, but around 25% of new HIV cases are regimen-resistant (DoH 2001). Hence, HIV remains a life-threatening and lifelong infection.

Medication adherence is crucial for successful treatment, i.e. clinically significant viral load reduction (Lopez et al. 2007). However, maintaining optimal levels of adherence over a lifetime is difficult (Cooper et al. 2009). Obtaining the full benefits of ART is a complex individual behavioural process determined by many broader factors including patient attributes and health care systems. Human behaviours and beliefs are also critical: Inadequate knowledge and negative attitudes towards ART, drug side effects, financial constraints, service-related factors, stigma, discrimination, inability to disclose HIV status and various socio-cultural issues may prevent patients from seeking treatment or maintaining adherence to it (Kgatlwane et al. 2005; Mills et al. 2006b; Nordqvist et al. 2006; Hendershot et al. 2009; Murray et al. 2009; Sanjobo et al. 2009). Despite ‘a paucity of data to guide the implementation of adherence intervention in clinical settings’ (Simoni et al. 2006), systematic reviews on aspects of adherence to ART have been conducted (DiMatteo 2004; Mills et al. 2006a,b; Simoni et al. 2006; Falagas et al. 2008; Malta et al. 2008; Hendershot et al. 2009) but not in Asian developing countries. Therefore, we reviewed published articles on factors affecting adherence to ART in Asia.

Methods

This review considered qualitative, quantitative and mixed-method studies that examined factors affecting adherence to ART for PLWH. Combining quantitative and qualitative studies in a systematic review may provide additional insights into links between theory and practice (Dixon-Woods et al. 2005). Qualitative research may provide detailed information on delivery of interventions, which is not the focus of quantitative studies. Therefore, this review included qualitative data from individual interviews and focus group discussions together with quantitative survey data. Considering both kinds of studies in a review may limit bias, improve reliability and enhance accuracy of recommendations (Mulrow 1994).

Inclusion and exclusion criteria

The population consisted of participants >18 years who had been prescribed ART. Data describing ART service providers were included to provide the staff’s perspective. The included studies considered populations from 24 Asian developing countries as defined by the World Bank (2010). Papers not written in English, published before 1996, review articles, policy documents and adherence training manuals were excluded.

Search and selection methods

We systematically searched Medline/Ovid, Cochrane library, CINAHL, Scopus, PyschINFO for English language articles published between which month? 1996 and December 2010 on factors influencing adherence to ART. We used the key words HIV or AIDS, antiretroviral or HAART or ARV, adherence or compliance, factor* or determin* or barrier*, facilitate* or motivate*, Asia. Reference lists of included papers were also checked, and citations in key papers were searched.

Study selection and data extraction

Two authors independently reviewed the retrieved studies at title and abstract level. Those articles meeting the inclusion criteria were critically appraised. A standard data extraction form was used, which covered both quantitative and qualitative researches. The data extraction form was developed using the Centre for Reviews and Dissemination guidance template (CRD 2009), which records basic information first (authors, date, title of paper and journal details), then detailed information about each study (study design, study location, aims of the study, study population, sample size and major findings) and reviewers’ comments. Data extraction was double-checked, and if necessary, amendments were made after discussion.

Quality appraisal and data synthesis

Included studies were assessed for quality and relevance to understanding the strengths and weaknesses of the body of evidence (Pawson 2008; CRD 2009). Quality assessment followed Hawker et al. (2002), whose tool is validated for both qualitative and quantitative systematic reviews in health care settings. Their checklist consists of 9 questions in each category with four degrees (good, fair, poor and very poor) of methodological quality ranging from 9 (very poor) to 36 (good). All articles were assessed to be of good methodological quality with scores ranging from 22 to 34. The included studies were read several times, and findings were coded and tabulated. Owing to the heterogeneity of the data (quantitative and qualitative), meta-analysis was not appropriate and a thematic synthesis was performed instead (Harden & Thomas 2005); the results are presented in table format (Dixon-Woods et al. 2005).

Results

Figure 1 shows that 12 articles were selected from the database search and six emerged from reference lists. All studies were conducted between 2004 and 2009. Papers were excluded on the grounds of not covering Asian developing countries, wrong age range, non-English language and addressing effectiveness of treatment rather than adherence. Twelve studies were quantitative, four were qualitative and two were mixed methods. The sample size of the studies ranged from 27 to 1,366. Ten of the 18 studies were from India (Kumarasamy et al. 2005; Safren et al. 2005; Shah et al. 2007; Sharma et al. 2007; Wanchu et al. 2007; Sarna et al. 2008; Cauldbeck et al. 2009; Sogarwal & Bachani 2009; Akhila et al. 2010; Venkatesh et al. 2010), four from China (Sabin et al. 2008; Starks et al. 2008, Wang et al. 2008; Wang et al. 2009), three from Thailand (Han et al. 2009; Li et al. 2010; Ruanjahn et al. 2010) and one from Cambodia (Spire et al. 2008) (Table I). All studies identified factors affecting adherence to ART, both negatively and positively (Appendices I and II).

Figure 1.

 Review of studies for inclusion.

Table I. Basic characteristics of the study
Author/yearStudy conducted yearLocation & settingStudy designSample size & sampling methodsMode of information collectionOutcome measured
  1. ART, Antiretroviral treatment.

Akhila et al. 2010 2006–2007India/hospitalQuantitative/survey313 (sampling procedure unclear)Not clearFactors affect the patient’s adherence to HAART
Cauldbeck et al. 2009 2006India/hospitalQuantitative/survey60 (sampling procedure unclear)Self-administered anonymous questionnaire surveyAssess the adherence to ART
Han et al. 2009 2009Thailand/hospitalQualitative/in-depth interview27 (purposive convenience sampling)In-depth interviewIdentify factors which facilitate or constrain on ART taking
Kumarasamy et al. 2005 Not statedIndia/private ARV treatment centreQualitative60 (sampling procedure unclear)Semistructured in-depth interviewAssess the barriers and facilitators on adherence to ART
Li et al. 2010 2007Thailand/hospitalQuantitative/survey507/ARV (sampling procedure unclear)Interview with structured questionnaireExamine the barriers that lead to non-adherence
Ruanjahn et al. 2010 2006Thailand/home/clinicMixed approach32 (purposive or judgmental sampling)Pre-tested self-reported adherence survey and semistructured interviewAssess the factors impeding adherence on ART
Sabin et al. 2008 2005–2006China/hospitalQualitative36 (sampling procedure unclear)Semistructured in-depth interview and FGDAssess barriers faced to ART adherence
Safren et al. 2005 Not statedIndia/clinicQuantitative/Survey304 (sampling procedure unclear)Self-reported questionnaireExamine non-adherence to ART and associate with any variables
Sarna et al. 2008 2004India/health facilitiesQuantitative/survey310 (sampling procedure unclear)Semistructured interview with pre-tested questionnaireExplore the factors associated with adherence
Shah et al. 2007 2004–2005India/3 private outpatients clinicsQuantitative/survey279 (convenience sampling)Structured interview with pre-tested questionnaireAssess the antiretroviral adherence
Sharma et al. 2007 2004–2005India/hospitalMixed approach226/purposive sampling (snow ball sampling)Semistructure questionnaire survey/interviewExplore adherence, access and impact amongst those who use ART
Sogarwal & Bachani 2009 2007India/27 ARV centresQuantitative/survey1366 (sampling procedure unclear)Face to face interviewAssess the antiretroviral treatment reasons for non-adherence
Spire et al. 2008 2004–2005Cambodia/hospitalQuantitative/survey346 (sampling procedure unclear)Individual face to face pre-tested standardizes questionnaire interviewEstimate the prevalence of non-adherence and identify the factors
Starks et al. 2008 Not statedChina/hospitalQualitative/in-depth interview29 (sampling procedure unclear)Semi structured in-depth interviewExplore barriers to and facilitators of antiretroviral adherence
Wanchu et al. 2007 2004–2005India/clinicQuantitative/survey200 (sampling procedure unclear)Self-reported questionnaire surveyDetermine adherence and reasons for missing medications
Wang et al. 2008 2006China/7 ART centresQuantitative/survey308 (sampling procedure unclear)Structured face to face surveyAssess the reasons for non-adherence
Wang & Wu 2007 2005China/rural areasQuantitative/Survey181 (sampling procedure unclear)Interviewer administered pre-tested questionnaireAssess the levels of adherence and determine the factors associated with suboptimal adherence
Venkatesh et al. 2010 Not statedIndia/clinicQuantitative/survey198 (sampling procedure unclear)Structured interviewer administered questionnaireExamine variables associated with ART non-adherence

Factors impeding adherence to ART

Twenty-two individual themes regarding factors impeding adherence were identified, comprising patient-related factors, socio-cultural factors and beliefs about medication, financial, health system and drug-related factors (Appendix I).

Eighteen studies described individual factors impacting on adherence encompassing personal trust, beliefs and motivation to take pills. Individual factors relating to non-adherence to treatment were the following: forgetting to take medication on time (eight studies) (Shah et al. 2007; Wanchu et al. 2007; Wang & Wu 2007; Sarna et al. 2008; Starks et al. 2008; Wang et al. 2008; Cauldbeck et al. 2009; Li et al. 2010), being too busy with other things (seven studies) (Safren et al. 2005; Shah et al. 2007; Wang & Wu 2007; Sarna et al. 2008; Wang et al. 2008; Han et al. 2009; Li et al. 2010), being away from home (six studies) (Safren et al. 2005; Shah et al. 2007; Wanchu et al. 2007; Sarna et al. 2008; Starks et al. 2008; Wang et al. 2008), not understanding treatment (five studies) (Wanchu et al. 2007; Starks et al. 2008; Wang et al. 2008; Han et al. 2009; Li et al. 2010), feeling depressed or overwhelmed (five studies) (Safren et al. 2005; Sabin et al. 2008; Sarna et al. 2008; Sogarwal & Bachani 2009; Akhila et al. 2010), concurrent substance misuse (including alcohol and drugs, four studies) (Safren et al. 2005; Sharma et al. 2007; Wang et al. 2008; Venkatesh et al. 2010) and wanting to be free of pills (two studies) (Starks et al. 2008; Wang et al. 2008). Furthermore, one study each identified sleeping in (Wang & Wu 2007), lack of motivation (Akhila et al. 2010), stopping pills after feeling better (Starks et al. 2008), involvement in socio-community activities (Wang & Wu 2007) and personal problem at home (Safren et al. 2005).

Socio-cultural factors preventing adherence to ART were the following: stigma and discrimination, fear of being recognized, fear of disclosure of status to community and fear of stigma from family (seven studies) (Kumarasamy et al. 2005; Wang & Wu 2007; Sabin et al. 2008; Starks et al. 2008; Wang et al. 2008; Akhila et al. 2010; Li et al. 2010). To prevent unwanted disclosure, participants hid their medication, which, in turn, led to either delayed or missed doses. Four studies reported that lack of family support led to non-adherence (Kumarasamy et al. 2005; Wanchu et al. 2007; Wang et al. 2008; Akhila et al. 2010).

Two studies reported that patients did not think pills were needed (Starks et al. 2008; Wang et al. 2008), one that pills were a burden (Wang & Wu 2007) and one that taking pills over a long period could lead to non-adherence (Venkatesh et al. 2010).

Thirteen studies reported non-adherence because of financial difficulties (Kumarasamy et al. 2005; Safren et al. 2005; Sharma et al. 2007; Wang & Wu 2007; Sabin et al. 2008; Sarna et al. 2008; Spire et al. 2008; Starks et al. 2008; Cauldbeck et al. 2009; Han et al. 2009; Sogarwal & Bachani 2009; Akhila et al. 2010; Ruanjahn et al. 2010). Transport, prescription charges, food costs and hospital diagnostic costs were also prominent reasons for patients failing to access their medication.

Health-system factors included inaccessibility of services and the relationship with service providers. Some health care delivery systems made it difficult to seek regular treatment. Eight studies reported that distance from home to health services caused problems (Sharma et al. 2007; Wanchu et al. 2007; Wang & Wu 2007; Sarna et al. 2008; Starks et al. 2008; Cauldbeck et al. 2009; Sogarwal & Bachani 2009; Li et al. 2010), and two studies found that inadequate counselling (limited instruction provided) (Wang & Wu 2007; Starks et al. 2008) prevented adherence.

Ten studies reported that drug side effects were an important reason for non-adherence (Kumarasamy et al. 2005; Safren et al. 2005; Shah et al. 2007; Sharma et al. 2007; Wanchu et al. 2007; Wang & Wu 2007; Sarna et al. 2008; Spire et al. 2008; Li et al. 2010; Ruanjahn et al. 2010). Two studies reported that the complexities of the medication regimens (Wang & Wu 2007; Ruanjahn et al. 2010) affected adherence to ART.

Factors facilitating adherence

Eleven themes were identified as facilitators or motivators of adherence to ART (Appendix II). Four studies mentioned that social support (Kumarasamy et al. 2005; Starks et al. 2008; Akhila et al. 2010; Ruanjahn et al. 2010), predominantly from partners, children and friends, played a significant role in increasing adherence. Three studies reported that self-efficacy (Kumarasamy et al. 2005; Starks et al. 2008; Akhila et al. 2010) and willingness to live longer (Kumarasamy et al. 2005; Starks et al. 2008; Ruanjahn et al. 2010) positively influenced adherence. Two studies noted that improved overall health (Kumarasamy et al. 2005; Starks et al. 2008), financial assistance (Kumarasamy et al. 2005; Ruanjahn et al. 2010) and being in higher income groups (Li et al. 2010; Ruanjahn et al. 2010) resulted in better adherence. Electronic reminders (Starks et al. 2008), obligation to live for family (Starks et al. 2008), good relationship with care providers (Starks et al. 2008), status disclosure (Spire et al. 2008) and worries regarding a fear of drug resistance (Starks et al. 2008) were other motivating factors.

Discussion

This review of both quantitative and qualitative studies reporting views of patients and health care providers on ART adherence revealed that individual factors such as simply forgetting, being too busy or depressed and substance misuse were common reasons for non-adherence (Kumarasamy et al. 2005; Shah et al. 2007; Sharma et al. 2007; Wanchu et al. 2007; Sabin et al. 2008; Sarna et al. 2008; Starks et al. 2008; Wang et al. 2008, 2009; Cauldbeck et al. 2009; Sogarwal & Bachani 2009; Li et al. 2010; Venkatesh et al. 2010). Regular patient follow-up and health carers giving attention during follow-up might help improve adherence. Patient-specific counselling may lead to better knowledge and, in turn, help to promote adherence. Asking patients to describe their daily behaviour may be helpful, and care providers could repeat instructions during follow-up appointments. Health care providers should provide personal support (reminders) or directly observe treatment to improve adherence rates.

Substance misuse was a determinant of non-adherence. Patients with concurrent substance misuse need direct observed therapy. Patients who are depressed could be advised to undergo psychological treatment before initiating ART. Patients’ self-efficacy, their desire to live longer and improve their overall health because of ART, motivated adherence (Kumarasamy et al. 2005; Starks et al. 2008; Akhila et al. 2010; Ruanjahn et al. 2010). This indicates that individual perceptions of ART effectiveness or visible signs that medications work are helpful to reinforce adherence (Adam et al. 2003).

We found that fitting the complex regimens into daily life and side effects of the drugs was an important reason for non-adherence, as were the toxicities and adverse side effects (varying from mild to severe and from acute to chronic) of ART drugs (Catz et al. 2000). One study reported that 92% of its study population were non-adherent because of the ART side effects (Altice et al. 2001). An individual’s belief about treatment, based on trust or mistrust, influences adherence (Wilson et al. 2002). The primary reason for medication discontinuation often was regimen intolerance (Melbourne et al. 1998), which shows how important it is to educate and counsel patients on how to cope with these side effects (Lewis et al. 2006). Trust in ART medication, self-awareness of one’s health and knowledge of the consequences of adherence and non-adherence are an important basis of trust and belief that can reinforce adherence despite ART side effects. Notably, all included papers date from the time span 2004 to 2009, when there was no significant variation in available regimens and patients were mostly prescribed first-line ART.

Twelve studies identified cost as a factor affecting non-adherence, confirming findings in other resource-limited settings (Mills et al. 2006a; Konkle-Parker et al. 2008; Bartlett & Shao 2009; Naik et al. 2009; Tuller et al. 2009). Having a higher income, better access points for repeat prescriptions, financial aid or support with travel costs generally improves adherence (Kumarasamy et al. 2005; Li et al. 2010; Ruanjahn et al. 2010). Addressing non-adherence to ART in Asian developing countries may, therefore, require different solutions from those in developed countries, where financial issues are not such a major concern. The countries included in this study varied in the range of governmental and non-governmental support available for ART treatment, which will have affected adherence.

This review shows that patients were embarrassed to take medication in front of others and concerned about their privacy when collecting repeat prescriptions. Patients who had not disclosed their HIV status, did not have support or were unable to disclose their status to others were more likely to be non-adherent (Ferguson et al. 2002; Kumarasamy et al. 2005; Rao et al. 2007; Wang & Wu 2007). PLWHs were unwilling to seek treatment at the nearest health institution because of fear of stigmatization (Adeneye et al. 2006). Negative community myths and beliefs about HIV were barriers to ART adherence elsewhere, too (Irwin et al. 2003).

Understanding the cultural issues is important for developing evidence-based interventions for patients with suboptimal adherence. Support from family members, including children, medication reminders and disclosing one’s ART status to others (family members, peers and society), had a positive influence on adherence (Spire et al. 2008). Owing to the fear of exclusion from their family and society, patients skipped medication if they had to take it in front of others. To avoid this, patients should be taught strategies on how to handle taking pills in secret. But governments should encourage a supportive environment where PLWHs do not have to worry about stigma and discrimination. Care and support, both emotional and medical, can help PLWHs lead a fulfilling life.

Good relationships with their care (Starks et al. 2008) or health service provider (Lewis et al. 2006) enabled patients to have better information about the importance of adhering to their regimes. Care providers who take time for explanations encourage a positive attitude; perhaps, time spent talking to significant influencing groups would also help to reinforce adherence (Coetzee et al. 2004; Aspeling & Van Wyk 2008). Acceptance, open communication, spending adequate time, cooperation and trust of health care providers enhanced adherence (Ickovics & Meade 2002a,b; Falagas et al. 2008). Thus, the responsibility for adherence to medication shifts from the patient to the service provider.

Conclusion

Adherence to ART varies over time and between individuals. In Asian developing communities, the factors impeding ART adherence are financial difficulties, stigma and discrimination, simply forgetting, being too busy, concurrent substance abuse and side effects. On the other hand, self-efficacy, family support and financial assistance facilitated adherence. Health care providers should give clear instructions and proper counselling to patients about how to manage ART if side effects occur. This review did not perform a meta-analysis and simply enumerated the impacting factors because of heterogeneity of the data (mixed studies). Drawing coherent conclusions was hampered by scarce data and methodological limitations because there are so few comparative studies. It remains unclear whether behavioural or educational interventions, drug treatments with fewer side effects or financial support is most powerful in enhancing adherence. This needs to be assessed in future.

Appendices

Appendix I: Factors negatively impacting on adherence

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Appendix II: Factors positevely impacing on adherence

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Ancillary