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REVIEW ARTICLE
Year : 2019  |  Volume : 63  |  Issue : 4  |  Page : 367-376  

Predictors of adherence to antiretroviral therapy among PLHIV


1 Associate Professor, Department of Community Health Nursing, Government College of Nursing, MMCRI, Mysore, Karnataka, India
2 Dean/Principal, Department of Community Health Nursing, Yenepoya Nursing College, Yenepoya Deemed to be University, Mangalore, Karnataka, India

Date of Web Publication18-Dec-2019

Correspondence Address:
Assoc Prof. Arjunahalli Eswarachar Paramesha
Government College of Nursing, MMCRI, Mysore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijph.IJPH_376_18

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   Abstract 


Adherence to antiretroviral therapy (ART) is of paramount importance to achieve the optimum control of viral load and progression of disease among people living with HIV (PLHIV). An overview of systematic reviews to summarize the factors influencing adherence to ART was not found in the literature; hence, the systematic review of systematic reviews was conducted to provide global view of factors influencing adherence to ART. Systematic reviews ever published till May 2018 were searched and retrieved between May 2015 and May 2018 from Cochrane and PubMed databases. Among 88 studies initially chosen based on inclusion and exclusion criteria, 22 were selected for further analysis. Qualitative analysis of included reviews was made through narrative synthesis approach. Results of the study show that among the 60 factors enlisted, 5 were most highly significant, 7 were highly significant, 19 were moderately significant, and 29 were emerged as significant factors. Substance abuse, financial constraints, social support, HIV stigma, and depressive symptoms were the most highly significant factors influencing the adherence, whereas age, employment status, long distance, side effects of drugs, pill burden, education, and mental health were regarded as highly significant factors influencing ART. Fatigue, away from home, being too busy in other things, simply forgot, and beliefs about the necessity of ART emerged as significant factors. The study concludes that findings from the overview give global insight into the factors determining adherence to ART which would further influence the innovations, program, and policy-making to mitigate the problem of nonadherence.

Keywords: Adherence, antiretroviral therapy, correlates, determinants, people living with HIV, predictors


How to cite this article:
Paramesha AE, Chacko LK. Predictors of adherence to antiretroviral therapy among PLHIV. Indian J Public Health 2019;63:367-76

How to cite this URL:
Paramesha AE, Chacko LK. Predictors of adherence to antiretroviral therapy among PLHIV. Indian J Public Health [serial online] 2019 [cited 2020 Jan 23];63:367-76. Available from: http://www.ijph.in/text.asp?2019/63/4/367/273360




   Introduction Top


Advancements in health-care technologies and revolutions of treatment modalities or breakthrough innovations in the diagnostics are not reducing the burden of morbidity among population up to the expectations. Majority of the preventable and manageable health problems, particularly chronic diseases requiring long-term treatment, are perpetually burdening the health-care delivery system. Poor adherence to the treatment is greatly associated with the burden of chronic diseases, which is estimated to be >65% of disease burden by the year 2020. Adherence is defined as the extent to which a person's behavior – taking medication, following a diet, and/or executing lifestyle changes – corresponds with agreed recommendations from a health-care provider.[1] Adherence to the treatment of chronic diseases is <50% and ranges between 37% and 83% for the treatment of HIV/acquired immunodeficiency syndrome (AIDS). Globally, 35.7 million are infected with HIV, of which 15 million are on antiretroviral therapy (ART). Poor adherence to ART leads to increased viral load, susceptibility to opportunistic infections, risk of transmission of infection, emergence of drug resistance and decreased quality of life, productivity, and life span besides causing waste of health-care resources.[2],[3],[4],[5],[6],[7],[8],[9]

Adherence to the lifelong treatment for HIV/AIDS is hindered by several factors resulting in need for second and tertiary line antiretroviral drugs. The factors influencing the adherence to ART are as complex as is the nature of HIV/AIDS originating from the person, society, health system, and the progressive disease condition. Recognition of factors influencing adherence to ART helps in reinforcing the conditions favoring adherence and limiting the factors, which hinders the adherence. Awareness of factors influencing the adherence enables the program planners to devise the strategies for providing optimal treatment and support services to people living with HIV (PLHIV) as well as prevents unnecessary efforts and expenditure related to treatment and support services. Recognition of exhaustive list of factors influencing adherence to ART therapy is possible by accumulating the evidence derived across the world through systematic reviews and their summaries.[1],[8]

Factors influencing the adherence refer to the antecedents for antiretroviral medicine taking behavior among PLHIV. The words “determinants,” “predictors,” and “correlates” are interchangeably used to denote the factors influencing the adherence to ART. Theoretical models, health-care-seeking behavior-related literature, provide insight into factors determining adherence to ART. Several schools of classification exist to categorize the factors such as system-related, condition-related, treatment-related, socioeconomic-related, and person-related factors.[3] Factors of intentional nonadherence and nonintentional nonadherence being another version of classification.[10] Both qualitative and quantitative systematic reviews are available to provide exhaustive list of factors as well as their correlation with the adherence to ART.

Sporadic systematic reviews across the world differ in their findings, and none of the studies is available to provide global view of factors influencing ART. This overview of systematic reviews intends to summarize the factors which influence the adherence to ART among PLHIV. The findings of this overview provide insight into the problem of nonadherence and enable the planning and designing of concrete measures based on the evidence. Development of interventions and assessment scales related to adherence behavior would be benefitted by this overview since it gives the comprehensive account of factors influencing ART.


   Methods Top


An overview of systematic review is done by following the typical steps of conducting systematic review. Major steps followed while conducting this overview of systematic reviews were location of sources, selection of reviews, and quality appraisal of reviews followed by presentation of findings. Systematic reviews ever published till May 2018 were searched and retrieved by the investigators between May 2015 and May 2018. A manual search was made among Cochrane review and PubMed databases using multiple variants of keywords such as factors, correlates, determinants, predictors, adherence, compliance, PLHIV, HIV survivors, ART, and HAART. Studies were selected for further review based on the inclusive criteria such as (i) the study conducted on PLHIV, (ii) individuals who were receiving highly active ART, (iii) adherence which was assessed using either objective or self-reported techniques, and (iv) studies with the objectives of assessing relationship between sociodemographic, geographical, psychological, clinical, economical factors and adherence to ART. Studies were excluded from the review based on the exclusive criteria such as (1) studies with nonavailability of full texts and (2) studies which are not systematic reviews. Quality appraisal of studies was made based on criteria similar to AMSTER tool such as extent of search made by the authors of individual reviews and measurement of required outcome variables.[11] Reviews based on systematic search of multiple databases and primarily measuring association of factors with the adherence of PLHIV to ART were considered suitable for the overview. Owing to heterogeneity of methods used in the individual reviews, only narrative synthesis of findings was made out of 22 systematic reviews. Even though there is likelihood of multiple counts of individual studies, selected systematic reviews represent 1085 studies and 763,842 individuals. After enlisting the significant factors identified in each review, a consolidated list of factors was prepared along with the weightage score corresponding to number of individual reviews representing each factor.


   Results Top


Manual review of adherence-related studies in Cochrane (8 studies) and PubMed (82 studies) databases yielded ninety studies. After excluding duplicates, there were 85 reviews related to adherence to ART. Initial screening of reviews excluded 61 reviews due to the nonavailability of free full texts and not specific to stated inclusive and exclusive criteria. Of 24 full texts chosen, 2 were excluded due to multiple outcome measures other than factors influencing adherence to ART [Figure 1]. The qualitative synthesis was found to be suitable and performed instead of performing meta-analysis due to heterogeneity of statistical methodology among selected studies. Among the included studies, twenty followed quantitative approach, one study being qualitative synthesis (Claborn, 2015), and one study followed the mixed-method approach (Sharada PW, 2012).
Figure 1: Review identification, screening, and selection for overview.

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Seven reviews intend to study the influence of broad range of factors upon adherence to ART (Nienke L, 2014; Sharada PW, 2012; Bulsara SM, 2018; Adejumo OA, 2015; Huan Z, 2016; Gesesew HA, 2017; and Costa JM, 2018), and two reviews study the influence of location on adherence (Feelemyer J, 2015, and Lankowski AJ, 2014), health literacy or knowledge (Cunha GH, 2017, and Lall P, 2015), and depression (Gonzalez JS, 2013, and Uthman OA, 2014). The remaining studies focus on specific factor such as livelihood security (Beth S, 2011), employment status (Jean BN, 2015), adverse events (AEs; Al-Dakkak I, 2013), socioeconomic factors (Karl P, 2013), depression (Gonzalez JS, 2013), stigma (Katz1 IT, 2013), food insecurity (Young S, 2014), treatment fatigue (Claborn KR, 2015), age (Ghidai L, 2013), and alcohol use (Azar MM, 2010) [Annexure Table 1].



Studies also differ in their approach to classify the factors influencing adherence to ART. Based on the intensity of relationship, factors are classified as strongest factor, major factors, moderate factors, and minor/insignificant factors (Nienke L, 2014). Widely accepted classification such as individual personal factors/beliefs, sociocultural/financial factors, health system-related factors and drug-related factors (Sharada PW, 2012), and developmental status of the country was considered as a predictor in terms of developed and developing countries (Bulsara SM, 2018; Huan Z, 2016; and Karl P, 2013) and financial status among low-middle-income countries in terms of financial capital, human capital, social capital, and reported barriers (Beth S, 2011). AEs influencing adherence were classified as general AEs, mental health AEs, sensory AEs, and gastrointestinal AEs (Al-Dakkak I, 2013) [Annexure Table 2].



Qualitative analysis of included reviews was made through narrative synthesis approach. Significant findings from selected reviews were summarized [Annexure Table 2] out of which an exhaustive list of factors influencing adherence to ART was prepared. Out of total 65 factors enlisted, those related to similar theme were represented by the most widely recognized type of factor to get the final list with 60 factors. The frequency distribution of listed factors based on the number of their source reviews was prepared [Table 1]a and [Table 1]b. The magnitude of literature supporting each predictor is presented in terms of percentages [Figure 2]. Factors which are represented in six or more reviews are considered as most highly significant factors influencing adherence to ART followed by highly significant factors if they are represented by 4–5 reviews, moderately significant factors which are found among 2–3 reviews, and significant factors which are found in at least one review. Among the total 60 factors enlisted, 5 were most highly significant, 7 were highly significant, 19 were moderately significant, and 29 were emerged as significant factors. Substance abuse (alcohol/drug),[12],[13],[14],[15],[16],[17],[18] financial constraints,[12],[13],[14],[15],[19],[20],[21] social support, HIV stigma,[12],[13],[14],[15],[19],[22] and depressive symptoms [12][,13],[18],[23],[24],[25] were most highly significant factors influencing the adherence, whereas age,[12],[15],[19],[26],[27] employment status,[14],[18],[20],[21],[28] long distance,[13],[15],[18],[20],[29] side effects of drugs,[13],[15],[18],[30],[31] pill burden,[12],[13],[15],[18],[31] education,[20],[21],[25],[32] and mental health [14],[15],[19],[30] were regarded as highly significant factors influencing ART. Fatigue,[18],[30],[31] away from home/social activities,[13],[18],[20] being too busy in other things,[13],[15],[20] simply forgot,[13],[15],[27] beliefs about the necessity/utility of ART,[12],[15],[19] living conditions,[15],[25],[29] food,[15],[20],[33] domestic violence,[15],[19],[20] and regimen [12],[13],[32] were emerged as highly significant factors.


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Figure 2: Distribution of predictors according to the percentage of source systematic reviews.

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   Discussion Top


A narrative synthesis of included reviews yielded four categories of factors classified according to their potential impact on adherence to ART. Most highly significant, highly significant, moderately significant, and significant factors listed in this overview are in relevance with the existing review of literature.

The results from this overview show that most highly significant factors influencing the adherence to ART being substance abuse, financial constraints, social support, stigma, and depression projects as major challenges to achieve optimum adherence to ART. Substance abuse emerged as the second most significant correlate of adherence in a large systematic review including 207 studies and sample size of more than one lakh (standardized mean difference (SMD) = −0.395, P = 0.001), whereas the reviews conducted in Asia (4/18 studies) and the review from India (1/8 studies) highlighted as a moderate and least significant factor, respectively.[12],[13],[34] Financial constraint in terms of cost emerged as the most significant factor in Asian (13/18 studies) and Indian (4/8) reviews, whereas the small impact is observed in a global review (SMD = −0.187, P = 0.025).[12],[13],[34] One of the most highly significant factors, HIV/AIDS stigma, plays a major role in treatment adherence across the globe irrespective of population characteristics. Seventy-five percent of the PLHIV experienced the stigma in Kenya,[35] around 50% in China,[36] and about 1/3 of PLHIV in southern India,[37] whereas global stigma negatively influences adherence to ART (SMD = −0.282, P = 0.001).[12] Social support refers to multiple resources, which positively influences adherence to ART as evident by a significant positive correlation between social support and adherence (SMD = 0.237, P = 0.001). Depressive symptoms interfere with treatment-seeking behavior by negatively influencing the adherence to ART (SMD = −0.305, P = 0.001).[12]

Even though quantitative estimate of influence of age on adherence found to be of small effect [12] (SMD = 0.118, P = 0.02) in the literature it is emerged as a highly significant factor in this review. Nonadherence to ART was found to be reduced by 27% among the older age group of PLHIV.[27] Some studies relate employment status with financial constraints and estimate as a predictor of nonadherence with small effect (SMD = −0.187, P = 0.001) whereas found significant among high- and low-income countries (odds ratio (OR): 1.33, OR: 1.85) and nonsignificant in middle-income countries (OR: 0.94).[ 28] Long distance from the ART center leads to increased time and cost of transportation. Even though PLHIV prefers to get ART from the centers which are far away from their domiciliary settings or native places, quantitative estimate from a review shows the negative influence of distance on adherence to ART (46%), and conclusive findings could not found among 50% of studies.[29] Side effects include transient events such as nausea, vomiting, and diarrhea and even long-term effects such as lipodystrophy. A study shows that for every additional AE, odds of nonadherence increases by 1.13 (confidence interval [CI]: 1.03–1.24).[38] Number of pills being consumed per day found to be negative correlate of adherence to ART (SMD = −0.124) in the literature whereas emerged as the highly significant factor in this overview. Education and knowledge of treatment enhances the understanding the nature of disease and treatment. A landmark study from India highlights the negative influence of illiteracy on adherence to ART (OR = −1.341).[39] Mental health and adherence to the treatment mutually influence one another where mental health provides positivity in seeking treatment and adherence helps in prevent the progression of disease and associated cognitive complications.[40]

Moderately significant factors are highlighted by 2–3 systematic reviews and can be further discussed under patient-related, social/economic-related, therapy-related, and health system-related factors. Patient-related factors can be further summarized as biological variables such as gender and fatigue; psychological variables such as beliefs about necessity, forgetfulness, coping ability, health literacy, and difficulties in understanding the treatment; and social variables such as marital status, away from home, disclosure to others, and being busy in social activities. Social/economic-related factors include living conditions, food security, domestic violence, and cost of transportation, whereas therapy-related factors include type of regimen and duration of treatment. Inadequate counseling services belong to health system-related factors.

Significant factors are recognized by at least one review and include patient-related issues such as competency, anxiety, confusion, change in routine, positive future expectations, concerns about ART, tobacco use, sexual dysfunction, personal problems at home, stopped after feeling well lack of motivation and memory. Social/economical factors were partners HIV status, poverty, travel time, rural residence, and family size, whereas therapy-related factors include daily dosing and time since diagnosis. Practical difficulties, trust/satisfaction with health-care providers, and linkage services are the health system-related factors, and the disease condition-related factors consist of neurocognitive factors, somatic problems, tuberculosis (TB)-HIV association, bedridden condition, cough, progressive nature of disease, and sleepiness.

Limitations

Reviews included in this study are not an exhaustive summary of factors influencing ART since many reviews were excluded due to nonavailability of full texts. Even though the target populations of selected reviews differ in their characteristics summary of findings were made based on common variables among the reviews such as PLHIV, ART and Adherence. Among few factors, despite possibility of grouping related factors, intentionally, the subgroups are distinctly highlighted to reinforce the relative importance of factors, for example, mental health, depressive symptoms, and substance abuse.


   Conclusion Top


Adherence to the treatment being the basis for the success of ART needs to be strengthened by addressing all the influencing factors of adherence. Compared with the magnitude of morbidity, mortality, loss of human productivity, and drain of health resources caused by uncontrolled progression of disease associated with nonadherence to the treatment, any number of efforts to curb the problem is valuable. Prioritization of factors influencing the adherence helps in optimum use of health-care resources and overviews such as this provides adequate evidence to focus on relevant determinants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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