Socioeconomic factors in adherence to HIV therapy in low- and middle-income countries.

It is not clear what effect socioeconomic factors have on adherence to antiretroviral therapy (ART) among patients in low- and middle-income countries. We performed a systematic review of the association of socioeconomic status (SES) with adherence to treatment of patients with HIV/AIDS in low- and middle-income countries. We searched electronic databases to identify studies concerning SES and HIV/AIDS and collected data on the association between various determinants of SES (income, education, occupation) and adherence to ART in low- and middle-income countries. From 252 potentially-relevant articles initially identified, 62 original studies were reviewed in detail, which contained data evaluating the association between SES and adherence to treatment of patients with HIV/AIDS. Income, level of education, and employment/occupational status were significantly and positively associated with the level of adherence in 15 studies (41.7%), 10 studies (20.4%), and 3 studies (11.1%) respectively out of 36, 49, and 27 studies reviewed. One study for income, four studies for education, and two studies for employment found a negative and significant association with adherence to ART. However, the aforementioned SES determinants were not found to be significantly associated with adherence in relation to 20 income-related (55.6%), 35 education-related (71.4%), 23 employment/occupational status-related (81.5%), and 2 SES-related (100%) studies. The systematic review of the available evidence does not provide conclusive support for the existence of a clear association between SES and adherence to ART among adult patients infected with HIV/ AIDS in low- and middle-income countries. There seems to be a positive trend among components of SES (income, education, employment status) and adherence to antiretroviral therapy in many of the reviewed studies.


INTRODUCTION
The clinical efficacy of antiretroviral therapy (ART) in suppressing the HIV virus and improving survival rates for those living with HIV has been welldocumented (1)(2)(3). However, successful antiretroviral therapy is dependent on sustaining high levels of adherence (correct dosage, taken on time, and in the correct way-either with or without food). The minimum level of adherence required for antiretro-viral drugs to work effectively is 95% (4). Although more potent antiretroviral regimens can allow for effective viral suppression at moderate levels of adherence, no or partial adherence can lead to the development of drug-resistant strains of the virus (5)(6)(7). Adherence to ART is influenced by factors associated with the patient, the disease, the therapy, and the relationship of the patient with healthcare provider (8)(9)(10). Patient-related factors include socioeconomic status (SES) (8,10).
A review of studies since 2005 on SES and adherence to ART primarily in high-income countries, did not provide conclusive support for a clear association between SES and adherence (8). However, it is not clear what effect socioeconomic factors have on adherence to ART in low-and middle-income

Socioeconomic Factors in Adherence to HIV Therapy in Low-and Middle-income Countries
countries. A possible association between SES and adherence to ART among HIV patients may have an impact on the success of their treatment (8,10).

Literature search
We performed a systematic search of the literature to identify reviews and original studies that reported data on the impact of SES on adherence to ART. The relevant studies were identified by the use of electronic databases, such as MEDLINE, EMBASE, SCI Web or Science, NLM Gateway, and Google Scholar. The last search was conducted in November 2011. In addition, relevant articles from the list of references of the initially-retrieved papers were identified. Studies conducted only in low-and middle-income countries were included, according to World Bank classifications (11). Five different search strategies using the following key words were employed: (i) Socioeconomic status AND (HIV OR AIDS) AND (compliance OR adherence), (ii) (Compliance OR adherence) AND (HIV OR AIDS) AND determinants, (iii) (AIDS OR HIV) AND (compliance OR adherence) AND education AND/OR income AND/OR occupation, (iv) (AIDS OR HIV) AND (compliance OR adherence) AND determinants, and (v) (AIDS OR HIV) AND (compliance OR adherence).
Defining socioeconomic status (SES) is difficult because a single, consistent unit of measurement was not used in the studies reviewed. Further, a debate exists in the public-health arena on the appropriate components of socioeconomic status and methods of measurement (12). Krieger et al. (13) have argued that it is important to distinguish two different components of socioeconomic position (actual resources and prestige or rank-related characteristics), and they preferred the use of the term 'socioeconomic position' instead of 'socioeconomic status'. In addition, they argued that it is important to collect data at the individual, household and neighbourhood level (12,13). Additional points emphasized included that data on individuals supported from 'annual family income' should be collected, measurements should incorporate the recognition that socioeconomic position can change over a lifetime, and measures of socioeconomic position may perform differentially based on racial/ethnic group and gender background (12,13). Most of the reviewed articles did not attend to these complexities, rather used one to three measures of SES, most often simplistic measures of income, education, and occupation or employment status. The reviewed articles were analyzed with the understanding that the complexities present in SES highlighted by Krieger et al. (13) should ideally be incorporated in future studies designed to tease out the relationship between SES and adherence to ART in low-and middleincome populations. Meanwhile, the term SES is used in this article rather than socioeconomic position, simply because this is how these measures were discussed by the authors in the papers reviewed (12). SES reflects different aspects of social stratification, and the traditional indicators at the individual level have been income, education, and occupation (14,15). There is no single-best indicator of SES suitable for all study objectives and applicable at all time-points in all settings. Each indicator measures different, often related aspects of socioeconomic stratification and may be more or less relevant to different health outcomes and at different stages in the course of life (15). Galobardes et al. (16) described the theoretical basis of the following three indicators used for measuring SES: (a) Education attempts to capture the knowledgerelated assets of a person. As formal education is normally completed in young adulthood and is strongly determined by parental characteristics, it can be conceptualized within a course of life framework as an indicator that, in part, measures socioeconomic position (SEP) in early life (16).
(b) Income is the indicator of SEP that most directly measures the material resources component (16).
(c) Occupation represents Weber's notion of SEP as a reflection of a person's place in society relating to their social standing, income, and intellect (16).

Selection of studies
The inclusion and exclusion criteria used for the reviewed studies were set before the literature search. Studies included in our study concerned only individual HIV-infected adult patients and their adherence to antiretroviral therapy. Reviews and editorials were not included in our systematic review. Studies that focused on HIVinfected illicit and/or licit drug-users and/or those with severe mental illness were excluded since such persons may need more creative approaches than other patients to ART adherence that differentiates them from the general popu-lation (8,(17)(18)(19). Two authors of the present article evaluated the eligibility studies obtained from the literature search using a predefined protocol. The two authors worked independently to scan all abstracts and obtained full-text articles. In cases of discrepancy, agreement was reached by consensus.

Data extraction
Two authors of the present article independently extracted and compiled the data. For each identified study that met the selection criteria, details were extracted on study design, characteristics of study population, data relevant to SES, the measure of adherence, the overall adherence, and findings regarding the association between determinants of SES and adherence on to an Excel spreadsheet. In this review, three parameters as major factors contributing to SES were assessed, namely income, education, occupation/employment status and their association with adherence to ART.
The following diagram presents the various steps in the process of selecting studies. 252 Potential relevant articles identified and screened for retrieval   The main parameters affecting SES (income, education, occupation) were only examined as a group comprising SES in two studies but, in 61 studies, these were rather regarded as socioeconomic characteristics. Therefore, many studies lacked data concerning some of the parameters. There were insufficient data regarding income in 26 studies ( 75,77), and three studies (11.1%) (28,29,77) respectively out of 36, 49, and 27 studies reviewed. Most significant findings refer to a positive association between levels of SES components and levels of adherence to antiretroviral treatment, although one for income (59), four for education (21,31,43,63) and two for employment (59,77) of the reviewed studies suggest an inverse association with adherence. However, the aforementioned SES determinants were not found to be significantly associated with adherence in relation to 20 income-related studies (

Limitations
This systematic review has several limitations. First, it was not possible to make a synthesis of the data, using the principles of meta-analysis due to the fact that there was considerable heterogeneity among the reviewed studies. Adherence was measured by different methods in each of the studies and the cutoff percentage of adherence to treatment between 'adherent' and 'non-adherent' varied among the studies. Another limitation was that the majority of the studies examined the used unreliable measures of adherence (self-report, in particular) as the adherence outcome measure. In addition, SES was not focused upon as a homogenous group of specific factors in most of the reviewed studies but was rather dispersed among its components, which were regarded as socioeconomic information. Therefore, partial data had to be collected regarding the association of such SES components, and adherence to antiretroviral therapy, where and if such an association was assessed. Occupation was mainly assessed in terms of employment status because often no data were given on status of occupation or working position of the patients (8).

Conclusions
The systematic review of the available evidence found a positive trend among components of SES (income, education, occupation/employment) and adherence to antiretroviral therapy in many of the reviewed studies. However, we found inconclusive support for a clear association between SES and adherence among patients infected with HIV/AIDS in low-and middle-income countries. The association between SES and adherence may differ depending on the cultural/economic/geographic context of the countries studied, and results emphasize a site-specific approach to adherence studies and programmes. Future studies should measure socioeconomic factors more accurately and, thus, may further explain the different impacts of SES to ART adherence. In the absence of a gold standard for measure of adherence, future studies should assess many outcomes.