Association between antiretroviral therapy adherence and employment status: systematic review and meta-analysis

Bull World Health Organ 2015;93:29–41 | doi: http://dx.doi.org/10.2471/BLT.14.138149 Systematic reviews 29 Association between antiretroviral therapy adherence and employment status: systematic review and meta-analysis Jean B Nachega,a Olalekan A Uthman,b Karl Peltzer,c Lindsey A Richardson,d Edward J Mills,e Kofi Amekudzif & Alice Ouédraogof Introduction Recent data from the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) indicate that access to human immunodeficiency virus (HIV) treat- ment and care services in low- and middle-income countries has expanded dramatically.1 In 2012, over 9.7 million people living with HIV in these countries were receiving antiretroviral therapy (ART).1 Despite this increase, ensuring adherence to HIV treat- ment remains challenging in all countries. A meta-analysis of patients in North America (n = 17 573) and Africa (n = 12 116) estimated that only 55% and 77% in these areas, respectively, achieved over 80% adherence2 and a global meta-analysis, which included 33 199 patients on ART, reported that only 62% achieved over 90% adherence.3 Common barriers to ad- herence include medication side-effects, pill burden, the need to disclose HIV serostatus, a perception of feeling well, treat- ment fatigue and structural and psychosocial factors.4,5 For individuals, nonadherence can result in virological treatment failure, the development of drug resistance, disease progression and death.6–9 At the community level, nonadherence makes HIV transmission more likely,10,11 can substantially increase health-care costs, particularly for hospitalization to treat op- portunistic infections,12 and can decrease productivity.13 One factor that has not been explored in depth is whether an indi- vidual’s employment status influences adherence to ART.14,15 Adherence to ART may be influenced by factors associated with the disease and its treatment, with the relationship between the patient and the health-care provider and with patients them- selves, such as socioeconomic status which is often based on em- ployment or occupational status in addition to educational level and income.14,16 Moreover, differences in adherence between peo- ple employed in the informal and the formal economy have been linked to gender roles and inequalities in employment status.17,18 A previous meta-analysis by our collaborative research group found that employed HIV-infected patients from low-, middle- and high-income countries were 39% more likely to adhere to ART than unemployed patients. However, the study included very few participants from middle- and low-income countries and therefore did not have sufficient statistical power to determine whether a country’s income level had a significant effect on the association between employment status and ART adherence.19 The aim of this systematic review and meta-analysis was to investigate the relationship between the employment status of HIV-infected individuals and ART adherence using updated data and a larger patient sample, which included more infor- mation from middle- and low-income countries. Methods This meta-analysis was reported in accordance with the Pre- ferred reporting items for systematic reviews and meta-Analyses: Objective To assess the association between the employment status of human immunodeficiency virus (HIV)-infected individuals and adherence to antiretroviral therapy (ART). Methods We searched the Medline, Embase and Cochrane Central Register of Controlled Trials databases for studies reporting ART adherence and employment status published between January 1980 and September 2014. Information from a wide range of other sources, including the grey literature, was also analysed. Two independent reviewers extracted data on treatment adherence and study characteristics. Study data on the association between being employed and adhering to ART were pooled using a random-effects model. Between-study heterogeneity and sources of bias were evaluated. Findings The meta-analysis included 28 studies published between 1996 and 2014 that together involved 8743 HIV-infected individuals from 14 countries. The overall pooled odds ratio (OR) for the association between being employed and adhering to ART was 1.27 (95% confidence interval, CI: 1.04–1.55). The association was significant for studies from low-income countries (OR: 1.85, 95% CI: 1.58–2.18) and high-income countries (OR: 1.33, 95% CI: 1.02–1.74) but not middle-income countries (OR: 0.94, 95% CI: 0.62–1.42). In addition, studies published after 2011 and larger studies showed less association between employment and adherence than earlier and small studies, respectively. Conclusion Employed HIV-infected individuals, particularly those in low- and high-income countries, were more likely to adhere to ART than unemployed individuals. Further research is needed on the mechanisms by which employment and ART adherence affect each other and on whether employment-creation interventions can positively influence ART adherence, HIV disease progression and quality of life. a Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, 503 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261, United States of America (USA). b Warwick Centre for Applied Health Research and Delivery, University of Warwick, Coventry, England. c Department of Psychology, University of Limpopo, Turfloop, South Africa. d Department of Sociology, University of British Columbia, Vancouver, Canada. e Stanford Prevention Research Center, Stanford University, Stanford, USA. f HIV/AIDS and the World of Work Branch (ILOAIDS), International Labour Organization, Geneva, Switzerland. Correspondence to Jean B Nachega (email: jbn16@pitt.edu). (Submitted: 4 March 2014 – Revised version received: 21 September 2014 – Accepted: 1 October 2014 – Published online: 30 October 2014 ) Systematic revi w Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.13814930 Systematic reviews Antiretroviral therapy adherence and employment Jean B Nachega et al. the PRISMA statement.20 Studies of any design were included if they satisfied the following criteria: (i) the study involved people living with HIV; (ii) participants were receiving highly active antiretro- viral therapy; (iii) treatment adherence was assessed using objective or self- reported measures; and (iv) employ- ment was considered a possible factor influencing adherence. We searched the Medline, Em- base and Cochrane Central Register of Controlled Trials databases for the period January 1980 to September 2014 (Box 1). In addition, we used a narrative literature review approach to analyse and summarize information on HIV treatment, particularly on adher- ence, from a range of sources including UNAIDS secretariat reports, scientific conference abstracts and other grey literature. We contacted individual researchers for details of unpublished studies. Two reviewers evaluated the eli- gibility of the studies identified and a third reviewer provided arbitration if there was a discrepancy. One reviewer extracted data, which were checked by others. The quality of the studies includ- ed was assessed using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS; details available from the corresponding author on request).21 The risk of bias in a study was graded as low, high or unclear on the basis of study features including the selection of par- ticipants (selection bias), consideration of confounding variables (selection bias), outcome measurement (detec- tion bias), incomplete outcome data (attrition bias) and selective outcome reporting (reporting bias). Data extraction For each study included, we recorded: the first author’s last name; the year of publication; the country where the study was performed; details of the study de- sign; the years when data were collected; the type of controls in case–control stud- ies; the duration of follow-up in cohort studies; sample size; details of exposure measures, such as indicators of occupa- tion or employment; age; sex; the odds that an employed patient versus an un- employed patient would adhere to ART; and the variables controlled for. Study countries were classified by geographical area and categorized as low-, middle- or high-income, as defined by the World Bank for 2014.22 Study participants were defined as being of working age either by the study investigators or using the International Labour Organization’s standard definition.23 In addition, the International Labour Organization’s definition of employment was applied: Persons in employment comprise all persons above a specified age who dur- ing a specified brief period, either one week or one day, were in the following categories: paid employment and self- employment.24 Consequently, studies were con- sidered eligible if their authors defined employed people as those who, during a specified brief period such as one week or one day: (i) performed some work for wage or salary in cash or in kind; (ii) had a formal attachment to a job but were temporarily not at work during the reference period; (iii) performed some work for profit or family gain in cash or in kind; or (iv) were with an enterprise such as a business, farm or service but who were temporarily not at work dur- ing the reference period for any specific reason.24 Data synthesis The meta-analysis was performed using the DerSimonian and Laird random- effects model to obtain a pooled esti- mate for the odds ratio (OR) and the associated 95% confidence interval (CI).25 The model was chosen since it takes into account both within- and between-study variability, as between- study heterogeneity was anticipated. Heterogeneity among studies was as- sessed by inspecting forest plots of the odds ratios from each study and by using the χ2 test for heterogeneity, with a 10% Box 1. Search terms used for studies on the association between employment status and adherence to antiretroviral therapy 1. hiv infections/ 2. HIV.ti. 3. human immunodeficiency virus.ti,ab. 4. HIV Infections/pc 5. HIV/ or HIV-1/ 6. Acquired Immunodeficiency Syndrome/pc [Prevention & Control] 7. exp hiv/ 8. exp hiv-1/ 9. exp hiv-2/ 10. Human immunodeficiency virus.mp. 11. hiv.mp. 12. or/ No. 1–11 13. blue collar.mp. 14. blue collar.ti,ab. 15. white collar.mp. 16. exp Social Class/ 17. exp Adult/ or Occupations/ 18. Agriculture/ec, ed, ma [Economics, Education, Manpower] 19. exp Employment/ 20. job.mp. 21. exp work/ 22. exp income/ 23. manpower.mp. 24. socioeconomic.mp. 25. socio-economic.mp. 26. office.mp. 27. or/No. 13–26 28. exp Medication Adherence/ 29. Adherence.mp. 30. Nonadherence.mp. 31. Compliance.mp. 32. or/ No. 28–31 33. No. 12 and 27 and 32 Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.138149 31 Systematic reviews Antiretroviral therapy adherence and employmentJean B Nachega et al. level of statistical significance, and the I2 statistic, with which a value of 50% represented moderate heterogeneity. We used leave-one-study-out sensitiv- ity analysis to evaluate the stability of the results and to test whether any one study had an excessive influence on the meta-analysis.26 In addition, we performed subgroup analyses to assess the influence of study design (i.e. cross- sectional versus prospective cohort), the country’s income group (i.e. low, middle or high), the adherence threshold and adherence measures. We used the χ2 test to subgroup differences and reported the P-value for interaction between pooled OR and study-level characteristics. We used a variance-weighted, least-squares regression approach to estimate the ef- fect of the year of publication (i.e. trend analysis) and the study sample size on the association between employment status and ART adherence. For all tests, a probability less than 0.05 was considered significant. All statistical tests were two- sided. Analyses were performed using Stata version 12 (StataCorp. LP, College Station, United States of America). Results A flow diagram of study selection is shown in Fig. 1. Twenty-eight studies, involving a total of 8743 patients from 14 countries, met criteria for inclusion in the systematic review (Table 1).4,27–53 The studies were carried out between 1996 and 2012 and publication took place between 1996 and 2014. Overall, 24 studies, involving 7484 of 8743 patients (86%), were cross-sectional, whereas the other four were prospective cohort studies. Eight studies, involving 1775 patients (20%), were carried out in the United States, three each were carried out in Ethiopia, India and South Africa and two were carried out in Uganda. Twenty-seven studies, involving 8008 patients (92%), included partici- pants who were already receiving ART. Twenty-three studies, involving 8171 patients (94%), defined adherence as receiving 95% or more of prescribed doses in a given period. In addition, 22 studies, involving 7755 patients (89%), used self-report questionnaires to assess adherence, whereas three used pharma- cy refill data, one used the pill count, one used the blood drug concentration and one used a combination of methods. The median sample size was 300 participants (range: 46–1016). When reported, the percentage of males ranged from 21.3% to 88.0% between studies. The median percentage of unemployed participants was 41% (range: 16–79%) and the per- centage of participants who adhered to ART ranged from 14.9% to 93.1%. Risk of bias The results of our assessment of the risk of bias in all studies included in the me- ta-analysis are shown in Fig. 2. The risk of bias in the selection of participants was low in all studies. However, the risk of selection bias due to inadequate confirmation or consideration of con- founding variables was low in 16 studies but high in 12: 16 studies adjusted for major confounding variables during the analysis phase, whereas the remaining 12 reported unadjusted associations between employment status and adher- ence to ART. The risk of detection bias due to inadequate outcome assessment was low in the six studies that assessed adherence using objective measures and high in the remaining 22, which used self-report questionnaires. The risk of attrition bias due to inadequate outcome data handling was low in 24 studies, unclear in two and high in the two studies in which more than 20% of patients were lost to follow-up. The risk of selective reporting bias was low in all studies. Association between adherence and employment The strength of the association between being employed and adhering to ART reported in each study in low-, middle- and high-incomes countries is shown in Fig. 3, Fig. 4 and Fig. 5, respectively. The figures also give pooled estimates for the association in each income group. The pooled estimate for the OR in all countries was 1.27 (95% confi- dence interval, CI: 1.04–1.55). There was evidence of substantial statistical heterogeneity between the results of all studies (I2: 77%). The leave-one-study- out sensitivity analysis showed that no single study had an undue influence on the pooled estimate. Associations in subgroups The magnitude and strength of the as- sociation between being employed and adhering to ART varied by country in- come group: it was highest in the seven studies from low-income countries, for which the pooled estimate for the OR was 1.85 (95% CI: 1.58–2.18). In the 11 studies from middle-income countries, the association was not significant as the pooled estimate for the OR was 0.94 (95% CI: 0.62–1.42). However, the asso- ciation was significant in the 10 studies from high-income countries: the pooled estimate for the OR was 1.33 (95% CI: 1.02–1.74). In addition, the strength of the association was significantly higher in prospective cohort studies than in cross-sectional studies: the pooled OR was 2.05 (95% CI: 1.50–2.81) and 1.17 (95% CI: 0.95–1.44) for the two study types, respectively (P-value for interaction = 0.003). The association was significant in studies that used an adherence threshold less than 100% (OR: 1.59, 95% CI: 1.35–1.87) but not Fig. 1. Flowchart showing the selection of studies for the meta-analysis of the association between employment status and adherence to antiretroviral therapy Records remaining after duplicates removed (n = 8322) Records identified in the literature search (n = 11 537) Records screened (n = 8322) Records excluded as they did not meet inclusion criteria (n = 8150) Articles whose full text was assessed for eligibility (n = 172) Articles excluded on full text assessment – none reported a relevant outcome (n = 144) Studies included in the meta-analysis (n = 28) Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.13814932 Systematic reviews Antiretroviral therapy adherence and employment Jean B Nachega et al. Ta bl e 1. St ud ie s i n th e m et a- an al ys is of th e as so cia tio n be tw ee n em pl oy m en t s ta tu s a nd a dh er en ce to a nt ire tr ov ira l t he ra py , 1 4 co un tr ie s, 19 96 –2 01 4 Fi rs t a ut ho r of st ud y Ye ar o f pu bl i- ca tio n St ud y p er io d St ud y d es ig n St ud y co un tr y Co un tr y’s in co m e gr ou pa Pa rt ici pa nt s re ce iv in g AR T at e nr ol m en t Lo w er th re sh ol d fo r ad he re nc e to AR T, % Ad he re nc e m ea su re Sa m pl e siz e, n M al e pa rt ic- ip an ts , % Ag e of pa rt ici pa nt s,b ye ar s Un em pl oy - m en t, % % A RT ad he r- en ce M ea su re o f as so cia tio nc Si ng h2 7 19 96 N ot re po rt ed Pr os pe ct iv e co ho rt U ni te d St at es H ig h Ye s 80 Ph ar m ac y re fil l da ta 46 N D 23 –6 8 41 .0 63 .0 U na dj us te d Si ng h2 8 19 99 M ar ch 1 99 6 to D ec em be r 19 97 Cr os s- se ct io na l U ni te d St at es H ig h Ye s N ot re po rt ed Ph ar m ac y re fil l da ta 12 3 N D 24 –7 1 52 .8 82 .1 U na dj us te d D uo ng 29 20 01 N ot re po rt ed Cr os s- se ct io na l Fr an ce H ig h Ye s N ot re po rt ed Bl oo d dr ug co nc en tra tio n 14 9 71 .8 21 –7 9 45 .6 89 .0 U na dj us te d Ic ko vi cs 30 20 02 N ot re po rt ed Cr os s- se ct io na l f ro m RC T U ni te d St at es H ig h Ye s 95 Se lf- re po rt qu es tio nn ai re 93 88 .0 19 –6 1 23 .9 63 .0 Ad ju st ed N ac he ga 31 20 04 N ot re po rt ed Cr os s- se ct io na l So ut h Af ric a M id dl e Ye s 95 Se lf- re po rt qu es tio nn ai re 66 28 .8 36 .1 (1 0. 1) 40 .9 88 .0 U na dj us te d Be ye ne 32 20 09 Au gu st to O ct ob er 2 00 9 Cr os s- se ct io na l Et hi op ia Lo w Ye s 95 Se lf- re po rt qu es tio nn ai re 42 2 43 .6 32 .2 (7 .2 ) 59 .0 93 .1 Ad ju st ed D ug ga n3 3 20 09 Au gu st to N ov em be r 20 06 Cr os s- se ct io na l U ni te d St at es H ig h Ye s N ot re po rt ed Co m bi na tio n of m et ho ds 13 2 66 .7 18 –5 1 55 .3 74 .2 U na dj us te d N ak im ul i- M pu ng u3 4 20 09 N ot re po rt ed Cr os s- se ct io na l U ga nd a Lo w Ye s 90 Se lf- re po rt qu es tio nn ai re 12 2 21 .3 36 .0 (8 .2 ) 34 .4 82 .8 Ad ju st ed Ca m po s3 5 20 10 M ay 2 00 1 to M ay 2 00 2 Pr os pe ct iv e co ho rt Br az il M id dl e Ye s 95 Se lf- re po rt qu es tio nn ai re 29 3 65 .9 N D 35 .1 62 .8 Ad ju st ed Gi da y3 6 20 10 Au gu st to Se pt em be r 20 08 Cr os s- se ct io na l Et hi op ia Lo w Ye s 95 Se lf- re po rt qu es tio nn ai re 51 0 38 .6 15 –6 3 39 .6 88 .2 Ad ju st ed Ku nu ts or 37 20 10 N ot re po rt ed Pr os pe ct iv e co ho rt U ga nd a Lo w Ye s 95 Ph ar m ac y re fil l da ta 39 2 35 .2 32 –4 5 55 .4 93 .1 Ad ju st ed La l38 20 10 20 05 Cr os s- se ct io na l In di a M id dl e Ye s 95 Se lf- re po rt qu es tio nn ai re 30 0 72 .0 30 –4 5 31 .8 75 .7 U na dj us te d Li 39 20 10 N ot re po rt ed Cr os s- se ct io na l f ro m RC T Th ai la nd M id dl e Ye s 10 0 Se lf- re po rt qu es tio nn ai re 38 6 32 .7 38 .0 (6 .4 ) 15 .5 68 .6 Ad ju st ed Pe ltz er 40 20 10 O ct ob er 2 00 7 to F eb ru ar y 20 08 Cr os s- se ct io na l So ut h Af ric a M id dl e N o 95 Se lf- re po rt qu es tio nn ai re 73 5 29 .8 N D 59 .6 82 .9 U na dj us te d Sh er r41 20 10 20 05 to 2 00 6 Cr os s- se ct io na l U ni te d Ki ng do m H ig h Ye s 10 0 Se lf- re po rt qu es tio nn ai re 44 9 78 .9 N D 42 .8 42 .8 U na dj us te d (c on tin ue s. . . ) Jean B Nachega et al. Antiretroviral therapy adherence and employment Systematic reviews 33Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.138149 Fi rs t a ut ho r of st ud y Ye ar o f pu bl i- ca tio n St ud y p er io d St ud y d es ig n St ud y co un tr y Co un tr y’s in co m e gr ou pa Pa rt ici pa nt s re ce iv in g AR T at e nr ol m en t Lo w er th re sh ol d fo r ad he re nc e to AR T, % Ad he re nc e m ea su re Sa m pl e siz e, n M al e pa rt ic- ip an ts , % Ag e of pa rt ici pa nt s,b ye ar s Un em pl oy - m en t, % % A RT ad he r- en ce M ea su re o f as so cia tio nc Ve nk at es h4 2 20 10 Ja nu ar y to A pr il 20 08 Cr os s- se ct io na l In di a M id dl e Ye s 95 Se lf- re po rt qu es tio nn ai re 19 8 68 .5 N D 21 .9 49 .0 Ad ju st ed H ar ris 43 20 11 Ju ne 2 00 4 to D ec em be r 2 00 5 Cr os s- se ct io na l D om in ic an Re pu bl ic M id dl e Ye s 95 Se lf- re po rt qu es tio nn ai re 30 0 45 .0 N D 53 .0 76 .0 U na dj us te d Ju da y4 20 11 Ap ril to M ay 20 07 Cr os s- se ct io na l U ni te d St at es H ig h Ye s 10 0 Se lf- re po rt qu es tio nn ai re 46 1 76 .1 44 .4 (9 .3 ) 56 .2 54 .0 Ad ju st ed Ky se r44 20 11 M ar ch 2 00 4 to Ju ne 2 00 6 Pr os pe ct iv e co ho rt U ni te d St at es H ig h Ye s 10 0 Se lf- re po rt qu es tio nn ai re 52 8 78 .0 20 –6 6 41 .0 84 .0 Ad ju st ed W ak ib i45 20 11 N ov em be r 20 08 to A pr il 20 09 Cr os s- se ct io na l Ke ny a Lo w Ye s 95 Se lf- re po rt qu es tio nn ai re 40 3 35 .0 18 –6 4 34 .0 82 .0 U na dj us te d Ki ng 46 20 12 Fe br ua ry 2 00 7 to D ec em be r 20 09 Cr os s- se ct io na l f ro m RC T U ni te d St at es H ig h Ye s 10 0 Se lf- re po rt qu es tio nn ai re 32 6 72 .1 45 .9 (7 .6 ) 79 .0 60 .4 Ad ju st ed Ki ts ho ff4 7 20 12 N ot re po rt ed Cr os s- se ct io na l So ut h Af ric a M id dl e Ye s 95 Pi ll co un t 14 6 27 .4 31 –4 2 65 .0 68 .0 Ad ju st ed Be rh e4 8 20 13 Au gu st 2 01 2 to O ct ob er 2 01 2 Cr os s- se ct io na l Et hi op ia Lo w Ye s 95 Se lf- re po rt qu es tio nn ai re 17 4 46 .0 38 .5 (8 .4 ) 20 .1 40 .8 Ad ju st ed O ko ro nk w o4 9 20 13 N ot re po rt ed Cr os s- se ct io na l N ig er ia M id dl e Ye s 10 0 Se lf- re po rt qu es tio nn ai re 22 1 N D N D 21 .8 14 .9 U na dj us te d Vi ss m an 50 20 13 N ov em be r 20 08 to A pr il 20 09 Cr os s- se ct io na l U ni te d St at es H ig h Ye s 10 0 Se lf- re po rt qu es tio nn ai re 66 74 .0 38 .0 (1 0. 3) 52 .0 71 .0 U na dj us te d Tr an 51 20 13 20 12 Cr os s- se ct io na l Vi et N am M id dl e Ye s 95 Se lf- re po rt qu es tio nn ai re 10 16 63 .8 35 .4 (7 .0 ) 17 .8 74 .1 Ad ju st ed Sa ha 52 20 14 20 11 Cr os s- se ct io na l In di a M id dl e Ye s 10 0 Se lf- re po rt qu es tio nn ai re 37 0 58 .4 33 .5 (8 .5 ) 33 .0 87 .6 Ad ju st ed Sh ig de l53 20 14 20 12 Cr os s- se ct io na l N ep al Lo w Ye s 95 Se lf- re po rt qu es tio nn ai re 31 6 64 .6 N D 22 .5 86 .7 Ad ju st ed AR T: an tir et ro vi ra l t he ra py ; N D : n ot d et er m in ed ; R CT : r an do m ize d co nt ro lle d tri al . a Co un tri es w er e ca te go riz ed a s l ow -, m id dl e- o r h ig h- in co m e, a s d efi ne d by th e W or ld B an k fo r 2 01 4. 22 b Pa rti ci pa nt s’ ag es a re g iv en a s a ra ng e or a s a m ea n (s ta nd ar d de vi at io n) . c W he th er o r n ot th e m ea su re o f t he a ss oc ia tio n be tw ee n em pl oy m en t s ta tu s a nd a dh er en ce to a nt ire tro vi ra l t re at m en t w as a dj us te d fo r m aj or c on fo un di ng v ar ia bl es . (. . . co nt in ue d) Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.13814934 Systematic reviews Antiretroviral therapy adherence and employment Jean B Nachega et al. in those that used a threshold of 100% (OR: 0.90, 95% CI: 0.64–1.26; P-value for interaction = 0.003). We also found that the type of adherence measure used did not significantly influence the association between being employed and adhering to ART: the pooled OR was 1.21 (95% CI: 0.98–1.51) for stud- ies that used self-report questionnaires compared with 1.67 (95% CI: 1.09–2.56) for those that used other measures (P- value for interaction = 0.19; Table 2). Period and study size effects The association between being employed and adhering to ART was observed to change over time, i.e. there was a period effect. The magnitude of the association declined with the publication year – the pooled OR for studies published be- tween 2011 and 2013 was lower than that for those reported before 2011 (Fig. 6). Similarly, we found that study size also significantly influenced the association, which was more pronounced in those with small samples (Fig. 7). For each additional 100 study participants, the magnitude of the association decreased by 9% (P = 0.001). Discussion Overall, we found that patients with HIV infections who were employed were 27% more likely to adhere to ART than those who were unemployed. This is in agreement with the results of our previous meta-analysis19 and of others5 who reported that one of the barriers to ART adherence in both developed and developing countries was financial constraints, which may be considered a proxy for unemployment. One differ- ence from our previous report is that the magnitude and strength of the as- sociation between being employed and adhering to ART were highest in studies from low-income countries. Hence, un- employment may have a greater effect on ART adherence in these settings. It is possible that employment facilitates adherence to HIV treatment because it is associated with, for ex- ample, increased social support, better structuring of time and improved psy- chosocial well-being – these associations have all been documented in the general population.54,55 A review of 16 longi- tudinal studies showed evidence that unemployment has a negative effect on mental health56 and other studies have found that depression and impaired psy- chosocial well-being are associated with poor ART adherence.57 Employment may also promote increased material well-being, for example, by improving food security and housing quality and by reducing poverty – all three are known to be associated with adherence to HIV treatment.5,58,59 In addition, employment may promote adherence to ART by improving access to medical services through employer-sponsored health programmes that specifically Fig. 2. Risk of bias in studies in the meta-analysis of the association between employment status and adherence to antiretroviral therapy, 14 countries, 1996–2014 Berhe 2013 Beyene 2009 Campos 2010 Duggan 2009 Duong 2001 Giday 2010 Harris 2011 Ickovics 2002 Juday 2011 King 2012 Kitshoff 2012 Kunutsor 2010 Kyser 2011 Lal 2010 Li 2010 Nachega 2004 Nakimuli-Mpungu 2009 Okoronkwo 2013 Peltzer 2010 Saha 2014 Sherr 2010 Shigdel 2014 Singh 1996 Singh 1999 Tran 2013 Venkatesh 2010 Vissman 2013 Wakibi 2011 Se lec tio n o f p ar tic ipa nt s ( se lec tio n b ias ) Study reference Co ns ide ra tio n o f c on fo un din g v ar iab les (s ele cti on bi as ) M ea su re m en t o f o ut co m e ( de te cti on bi as ) In co m ple te ou tco m e d at a ( at tri tio n b ias ) Se lec tiv e r ep or tin g ( re po rti ng bi as ) Low risk of bias High risk of bias Unclear risk of bias Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.138149 35 Systematic reviews Antiretroviral therapy adherence and employmentJean B Nachega et al. encourage HIV treatment and by hav- ing a positive effect on physical and mental health-related quality of life.5,60 Conversely, the association may, in part, be due to the positive effect of ART on an individual’s ability to find and retain employment, i.e. reverse causation. For example, it was found that HIV-infected workers who were not receiving ART were almost twice as likely to report being unable to work in the previous week than those who recently began and were adherent to ART.61 Another study on more than 2000 HIV-infected adults enrolled in an ART programme estimated that four years after ART initiation, employment had returned to about 90% of the rates observed in the same patients three to five years before ART initiation.62 Further prospective, longitudinal, cohort studies of employ- ment status, ART adherence and other factors could help tease out the relative effects of ART adherence and employ- ment on each other. Despite mutual reinforcement between employment and ART adher- ence, it can be difficult for individuals to maintain adherence. For example, it was found that the main reasons for the discontinuation of antiretroviral therapy in the workplace in South Africa were: individuals being uncertain about their own HIV status and about the value of ART; poor relationships between patients and health-care providers; and discrimination in the workplace.63 Fur- thermore, workplace participants also felt that the follow-up visits required by ART clinics created problems for them with their employers. The most fre- quently cited reason for treatment dis- continuation among these individuals was harassment and discrimination by line managers who refused to grant time off from work for clinic attendance. For public sector employees, the main rea- sons included relocation away from HIV care providers and having insufficient money for transportation to clinical fa- cilities.63 These findings suggest there is a considerable need to promote awareness of the importance of ART adherence and to develop employment arrangements among both employers and employees that encourage adherence. Adherence, employment and gender Unexpectedly, we found no evidence that gender had a significant influence on the association between employment status and ART adherence. Several fac- tors could account for this finding. There is a gender gap in access to antiretroviral therapy. In most areas of the world, and especially in settings with a high burden of HIV infection, women are more likely than men to access both ART and sup- portive HIV services, such as targeted counselling and programmes for the prevention of mother-to-child HIV transmission offered by antenatal ser- vices.64 Conversely, men may have better Fig. 3. Association between being employed and adhering to antiretroviral therapy in studies from low-income countries, 2009–2014 Study reference OR (95% CI) Beyene 2009 2.27 (0.95–5.44) Nakimuli-Mpungu 2009 1.32 (0.49–3.53) Giday 2010 2.01 (1.17–3.46) Kunutsor 2010 0.53 (0.08–3.72) Wakibi 2011 1.23 (0.72–2.09) Berhe 2013 1.98 (1.63–2.40) Shigdel 2014 1.68 (0.81–3.48) Subtotal (l2 = 0%, P < 0.01) 1.85 (1.58–2.18) Favours being employed 0.05 0.2 1 5 20 CI: confidence interval; OR: odds ratio. Fig. 4. Association between being employed and adhering to antiretroviral therapy in studies from middle-income countries, 2004–2014 Study reference OR (95% CI) Nachega 2004 0.44 (0.08–2.39) Campos 2010 2.10 (1.28–3.43) Lal 2010 0.96 (0.51–1.80) Venkatesh 2010 1.80 (0.90–3.62) Peltzer 2010 1.23 (0.77–1.97) Li 2010 0.62 (0.33–1.18) Harris 2011 1.40 (0.79–2.49) Kitshoff 2012 2.40 (0.97–5.93) Tran 2013 0.56 (0.23–1.36) Okoronkwo 2013 0.29 (0.15–0.57) Saha 2014 0.38 (0.16–0.92) Subtotal (l2 = 75%, P = 0.76) 0.94 (0.62–1.42) Favours being employed 0.05 0.2 1 5 20 CI: confidence interval; OR: odds ratio. Fig. 5. Association between being employed and adhering to antiretroviral therapy in studies from high-income countries, 1996–2013 Study reference OR (95% CI) Singh 1996 3.29 (0.77–14.0) Singh 1999 1.36 (0.53–3.47) Duong 2001 1.59 (0.56–4.53) Ickovics 2002 2.30 (0.83–6.35) Duggan 2009 1.48 (0.66–3.35) Sherr 2010 0.91 (0.63–1.33) Juday 2011 1.12 (0.69–1.82) Kyser 2011 1.88 (1.18–3.01) King 2012 0.97 (0.91–1.03) Vissman 2013 3.78 (1.17–12.2) Subtotal (l2 = 56%, P = 0.03) 1.33 (1.02–1.74) Favours being employed 0.05 0.2 1 5 20 CI: confidence interval; OR: odds ratio. Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.13814936 Systematic reviews Antiretroviral therapy adherence and employment Jean B Nachega et al. access to employment than women and employment could facilitate increased adherence among men.65,66 Period effect Our finding that the association between being employed and adhering to ART declined over time may reflect changes in ART regimens, such as the trend to- wards once-daily dosing, reductions in the pill burden and side-effects,67,68 better access to treatment for both employed and unemployed individuals or a drop in the cost of HIV medications.1 Further research is needed to determine whether this finding is specific to the studies we included or whether it signifies a true decrease in the association over time. Limitations The findings of this meta-analysis should be interpreted with caution. The observational nature of the data – 85% of the studies included had a cross- sectional design – limited our ability to draw causal inferences and our findings may be affected by reverse causation bias or by other unknown confound- ing factors that were not adjusted for. Additionally, we found significant heterogeneity across the studies, which suggests that a substantial percentage of the variability in effect estimates was due to heterogeneity rather than to sampling errors, i.e. to chance. Much of the heterogeneity observed may be explained by differences in the adher- ence threshold, study sample size and study design. Nevertheless, even when there is substantial heterogeneity, meta- analysis is regarded as preferable for data synthesis to qualitative or narrative interpretation since these approaches can lead to misleading conclusions that should not be generalized beyond the scope of the analysis.69 The ability to draw conclusions from quantitative data is an important feature of meta- analyses and its absence is one reason for avoiding narrative interpretations without a data synthesis. It is worth noting that the heterogeneity observed in the current study appears to be the norm rather than the exception in meta-analyses of ART adherence.14,15 An additional potential limitation is that none of the studies included compared treatment adherence across different types of occupation. Further, we found evidence for a small study ef- fect and it is possible that the observed magnitude of the association between being employed and adhering to ART could have been inflated by studies with small sample sizes. Despite these limitations, our study had important strengths. We conducted comprehensive searches of databases to ensure that all relevant, published stud- ies were identified. We also carried out meta-regression analyses to determine whether any particular study-level factor explained the results or could account for the observed variations between studies. In performing this comprehensive and robust review of the existing literature, we identified gaps in the current literature on determinants of ART adherence. Table 2. Association between being employed and adhering to antiretroviral therapy, by subgroup, 14 countries, 1996–2014 Subgroup No. of studies Pooled association Subgroup heterogeneity,a POR (95% CI) I2, %b Income groupc 0.003 Low 7 1.85 (1.58–2.18) 0 NA Middle 11 0.94 (0.62–1.42) 75 NA High 10 1.33 (1.02–1.74) 56 NA Study design 0.003 Cross-sectional 24 1.17 (0.95–1.44) 77 NA Prospective cohort 4 2.05 (1.50–2.81) 0 NA Adherence threshold 0.003 < 100% 20 1.59 (1.35–1.87) 17 NA 100% 8 0.90 (0.64–1.26) 78 NA Adherence measure 0.19 Self-report questionnaire 22 1.21 (0.98–1.51) 81 NA Other 6 1.67 (1.09–2.56) 0 NA ART: antiretroviral therapy; CI: confidence interval; NA: not applicable; OR: odds ratio. a Subgroups were compared using the χ2 test. b I2 indicates the heterogeneity between the results of the studies in the subgroup. c Countries were categorized as low-, middle- or high-income, as defined by the World Bank for 2014.22 Fig. 6. Association between being employed and adhering to antiretroviral therapy, by study publication year, 14 countries, 1996–2012 Od ds ra tio a 4 3 2 1 0 Publication year 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 Best fit Proportion to odds ratio variance Proportion to varianceb a The odds ratio represents the odds that an employed patient would adhere to treatment compared with an unemployed patient. b The area of each circle is in inverse proportion to the precision of the odds ratio. 73 941831.41.TLB/1742.01/gro.iod.xd//:ptth :iod |14–92:39;5102 nagrO htlaeH dlroW lluB sweiver citametsyS .la te agehcaN B naeJtnemyolpme dna ecnerehda ypareht larivorteritnA hcraeser erutuf rof saerA lla sserdda ot elbanu saw weiver ruO noitaicossa eht no snoitseuq tnenitrep lamitpo dna sutats tnemyolpme neewteb yduts ruO .tnemtaert VIH ot ecnerehda egnar a rof deen a etacidni sgnidnfi etagitsevni ot )i( :hcraeser rehtruf fo tnemyolpme hcihw yb smsinahcem ;rehto hcae tceffa ecnerehda TRA dna sepyt tnereffid woh enimreted ot )ii( -uflni yllaitnereffid nac tnemyolpme fo eht yduts ot )iii( ;ecnerehda TRA ecne neewteb noitcaretni dna noitaicossa -acidem ot ecnerehda dna tnemyolpme .g.e ,sesaesid dibromoc cinorhc rof snoit ni amhtsa dna setebaid ,noisnetrepyh ;slaudividni detcefninu ro detcefni-VIH fo seiduts lanoitnevretni tcudnoc ot )vi( semmargorp noitaerc-tnemyolpme woh tnemtaert VIH ecneuflni ylevitisop nac dna noissergorp esaesid ,ecnerehda -tsoc tuo yrrac ot )v( dna ;efil fo ytilauq sesylana ssenevitceffe-tsoc dna tfieneb -retni noitaerc-tnemyolpme detceles fo ■ .VIH htiw gnivil elpoep rof snoitnev stnemegdelwonkcA melasureyE ,ytrehoD geM knaht eW .ronnoC eniloraC dna eissugeN edebeK eht yb dedivorp saw gnidnuF :gnidnuF kroW fo dlroW eht dna SDIA/VIH lanoitanretnI eht fo )SDIAOLI( hcnarB .noitazinagrO ruobaL .deralced enoN :stseretni gnitepmoC ملخص الارتباط بين الالتزام بالعلاج بمضادات الفيروسات القهقرية وحالة التوظيف: استعراض منهجي وتحليل وصفي الغرض تقييم الارتباط بين حالة التوظيف لدى الأشخاص المصابين بعدوى فيروس العوز المناعي البشري والالتزام بالعلاج بمضادات الفيروسات القهقرية. الطريقة أجرينا بحثًا في قواعد بيانات enildeM وesabmE وسجل كوكرين المركزي للتجارب الخاضعة للمراقبة من أجل معرفة الدراسات التي أبلغت عن الالتزام بالعلاج بمضادات الفيروسات القهقرية وحالة التوظيف وتم نشرها في الفترة من كانون الثاني/يناير 0891 إلى أيلول/سبتمبر 4102. وتم كذلك تحليل المعلومات المستمدة من نطاق واسع من المصادر الأخرى، بما في ذلك الأبحاث غير الرسمية. واستخلص مراجعان مستقلان البيانات الخاصة بالالتزام بالعلاج وخصائص الدراسة. وتم تجميع بيانات الدراسة المعنية بالارتباط بين التوظيف والالتزام بالعلاج بمضادات الفيروسات القهقرية باستخدام نموذج التأثيرات العشوائية. وتم تقدير التغايرية بين الدراسات ومصادر التحيز. النتائج تضمن التحليل الوصفي 82 دراسة تم نشرها في الفترة من 6991 إلى 4102 والتي شملت معًا 3478 شخصًا مصابًا بعدوى فيروس العوز المناعي البشري من 41 بلدًا. وكانت نسبة الاحتمال المجمعة للارتباط بين التوظيف والالتزام بالعلاج بمضادات الفيروسات القهقرية بشكل عام 72.1 (فاصل الثقة 59 %، فاصل الثقة: من 40.1 إلى 55.1). وكان الارتباط كبيرًا بالنسبة للدراسات من البلدان المنخفضة الدخل (نسبة الاحتمال: 58.1، فاصل الثقة: 59 %، فاصل الثقة: من 85.1 إلى 81.2) والبلدان المرتفعة الدخل (نسبة الاحتمال: 33.1، فاصل الثقة: 59 %، فاصل الثقة: من 20.1 إلى 47.1) دون البلدان المتوسطة الدخل (نسبة الاحتمال: 49.0، فاصل الثقة: 59 %، فاصل الثقة: من 26.0 إلى 24.1). بالإضافة إلى ذلك، أوضحت الدراسات التي تم نشرها بعد عام 1102 والدراسات الأكبر نسبة ارتباط أقل بين التوظيف والالتزام عن الدراسات السابقة والصغيرة، على التوالي. الاستنتاج يرجح التزام الأشخاص المصابين بعدوى فيروس العوز المناعي البشري الموظفين، لا سيما في البلدان المنخفضة والبلدان المرتفعة الدخل، بالعلاج بمضادات الفيروسات القهقرية عن الأشخاص العاطلين. ويتعين إجراء المزيد من الأبحاث بشأن الآليات التي يؤثر من خلالها التوظيف والالتزام بالعلاج بمضادات الفيروسات القهقرية كل منهما على الآخر وبشأن ما إذا كان بإمكان تدخلات إيجاد التوظيف أن تؤثر إيجابيًا على الالتزام بالعلاج بمضادات الفيروسات القهقرية وعلى تفاقم مرض فيروس العوز المناعي البشري وعلى جودة الحياة. yb ,ypareht larivorteritna ot gnirehda dna deyolpme gnieb neewteb noitaicossA .7 .giF 2102–6991 ,seirtnuoc 41 ,ezis elpmas yduts dO sd ar oit a 4 3 2 1 0 1– 0011 0001 009 008 007 006 005 004 003 002 001 0 ezis elpmaS becnairav ot noitroporP ecnairav oitar sddo ot noitroporP tif tseB derapmoc tnemtaert ot erehda dluow tneitap deyolpme na taht sddo eht stneserper oitar sddo ehT a .tneitap deyolpmenu na htiw .oitar sddo eht fo noisicerp eht ot noitroporp esrevni ni si elcric hcae fo aera ehT b Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.13814938 Systematic reviews Antiretroviral therapy adherence and employment Jean B Nachega et al. 摘要 抗逆转录病毒疗法的坚持和就业状况之间的关联：系统回顾和元分析 目的 评估艾滋病病毒（HIV）感染个人的就业状况和 坚持抗逆转录病毒疗法（ART）之间的关联。 方法 我们搜索了 Medline、Embase 和 Cochrane 对照试 验中心注册数据库，寻找 1980 年 1 月至 2014 年 9 月 发表的报告 ART 坚持和就业状况的研究。也对来自其 他来源的广泛信息进行分析，其中包括灰色文献。由 两名独立评审者抽取有关坚持治疗和研究特点的数 据。使用随机效应模型汇聚有关受雇和坚持 ART 之间 关联性的研究数据。评估了研究间异质性和偏差来源。 结果 元分析包括了在 1996 年和 2014 年之间发布的 28 项研究，合计涉及来自 14 个国家的 8743 个 HIV 感染 个人。受雇和坚持 ART 之间关联的总体汇总优势比 （OR）为 1.27（95% 置信区间，CI ：1.04–1.55）。来自 低收入国家的研究的关联比较明显（OR ： 1.85，95% CI ：1.58–2.18）， 高 收 入 国 家 也 是 如 此（OR ： 1.33， 95% CI ：1.02–1.74），但中等收入则不然（OR ： 0.94， 95% CI ：0.62–1.42）。此外，在 2011 年之后发表的研 究和更大的研究显示出的就业和坚持治疗之间的关联 分别均比较早和较小研究更小。 结论 较之失业的个人，就业的 HIV 感染个人（尤其 在低收入和高收入国家）更可能坚持 ART。需要进一 步研究来了解就业和坚持 ART 相互影响的机制，以及 创造就业干预是否对坚持 ART、HIV 疾病恶化和生活 质量有积极的影响。 Résumé Lien entre le suivi de la thérapie antirétrovirale et le statut professionnel: revue systématique et méta-analyse Objectif Évaluer le lien entre le statut professionnel des personnes infectées par le virus de l’immunodéficience humaine (VIH) et le suivi de la thérapie antirétrovirale (TAR). Méthodes Nous avons effectué des recherches dans les bases de données de Medline, d’Embase et du registre central de Cochrane des essais contrôlés (Cochrane Central Register of Controlled Trials) pour trouver les études relatives au suivi de la TAR et aux statuts professionnels qui ont été publiées entre janvier 1980 et septembre 2014. Des informations provenant d’un large éventail de sources alternatives, y compris la littérature grise, ont également été analysées. Deux examinateurs indépendants ont extrait les données sur le suivi du traitement et les caractéristiques de l’étude. Les données de l’étude sur le lien existant entre le fait d’avoir un emploi et le suivi de la TAR ont été regroupées en utilisant un modèle à effets aléatoires. L’hétérogénéité entre les études et les sources de biais ont été évaluées. Résultats La méta-analyse a inclus 28 études publiées entre 1996 et 2014, qui, ensemble, ont impliqué 8743 personnes infectées par le VIH dans 14 pays. Le rapport des cotes (RC) regroupé global pour le lien entre le fait d’avoir un emploi et le suivi de la TAR était de 1,27 (intervalle de confiance à 95%, IC: 1,04–1,55). Ce lien était significatif pour les études dans les pays à revenu faible (RC: 1,85; IC 95%: 1,58–2,18) et dans les pays à revenu élevé (RC: 1,33; IC 95%: 1,02–1,74) mais il ne l’était pas dans les pays à revenu intermédiaire (RC: 0,94; IC 95%: 0,62–1,42). En outre, les études publiées après 2011 et les études plus vastes ont montré un lien moins fort entre le statut professionnel et le suivi thérapeutique que dans les études précédentes et les études plus restreintes, respectivement. Conclusion Les personnes infectées par le VIH et ayant un emploi, en particulier dans les pays à revenu faible et les pays à revenu élevé, étaient plus susceptibles de suivre la TAR que les personnes sans emploi. Des recherches plus approfondies sont nécessaires pour étudier les mécanismes par lesquels le fait d’avoir un emploi et le fait de suivre la TAR s’affectent mutuellement et pour savoir si les interventions favorisant la création d’emplois peuvent influencer positivement le suivi de la TAR, la progression de la maladie due au VIH et la qualité de vie. Резюме Связь между соблюдением режима антиретровирусной терапии и статусом занятости: систематический обзор и мета-анализ Цель Оценить связь между статусом занятости лиц, инфицированных вирусом иммунодефицита человека (ВИЧ), и соблюдением режима антиретровирусной терапии (АРТ). Методы Был произведен поиск работ в базах данных Medline, Embase и в Кокрановском центральном реестре контролируемых клинических исследований, содержащих данные о соблюдении пациентами режима АРТ и их статусе занятости, которые были опубликованы в период с января 1980 по сентябрь 2014 года. Также была проанализирована информация из широкого круга других источников, в том числе, литературы, не индексированной в медицинских базах данных. Данные о соблюдении режима лечения и характеристиках исследованиий отбирались двумя независимыми экспертами. Данные исследованиий о связи между занятостью и соблюдением режима АРТ были объединены с использованием модели случайных эффектов. Была оценена гетерогенность между исследованиями и источники ошибок. Результаты В мета-анализ было включено 28 исследований, опубликованных в период с 1996 по 2014 гг., которые в совокупности содержали данные по 8743 ВИЧ-инфицированным лицам из 14 стран. Суммарное обобщенное отношение шансов (ОШ) для связи между занятостью и соблюдением режима АРТ составило 1,27 (95%-ный доверительный интервал, ДИ: 1,04–1,55). Эта связь была существенной в исследованиях, выполненных в странах с низким уровнем дохода (ОШ: 1,85; 95%-ный ДИ: 1,58–2,18) и в странах с высоким уровнем дохода (ОШ: 1,33; 95%-ный ДИ: 1,02–1,74), но не в странах со средним уровнем дохода (ОШ: 0,94; 95%-ный ДИ: 0,62– 1,42). Кроме того, исследования, опубликованные после 2011 года, и более крупные исследования показали меньшую связь между занятостью и соблюдением режима терапии по сравнению с более ранними и меньшими по масштабу исследованиями соответственно. Вывод Имеющие трудовую занятость ВИЧ-инфицированные лица, особенно в странах с низким и высоким уровнем дохода, в большинстве своем, соблюдали режим АРТ, по сравнению с безработными лицами. Необходимы дальнейшие исследования механизмов взаимного влияния занятости на соблюдение режима АРТ, а также возможности положительного влияния мер по созданию занятости на соблюдение режима АРТ, прогрессирование ВИЧ-инфекции и качество жизни. Bull World Health Organ 2015;93:29–41| doi: http://dx.doi.org/10.2471/BLT.14.138149 39 Systematic reviews Antiretroviral therapy adherence and employmentJean B Nachega et al. Resumen La asociación entre la adherencia a la terapia antirretroviral y la situación laboral: examen sistemático y metaanálisis Objetivo Evaluar la relación entre la situación laboral de personas infectadas por el virus de la inmunodeficiencia humana (VIH) y la adherencia a la terapia antirretroviral (TAR). Métodos Se realizaron búsquedas de estudios publicados entre enero de 1980 y septiembre de 2014 que informaran acerca de la adherencia a la TAR y la situación laboral en las bases de datos Medline, Embase y el Registro Cochrane Central de Ensayos Controlados. También se analizó la información de una amplia gama de fuentes, entre ellas, la literatura gris. Dos revisores independientes extrajeron los datos sobre la adherencia al tratamiento y las características del estudio. Los datos de los estudios sobre la asociación entre el empleo y la adherencia a la TAR se agruparon por medio de un modelo de efectos aleatorios y se evaluó la heterogeneidad entre los estudios y las fuentes de sesgo. Resultados El metanálisis incluyó 28 estudios publicados entre 1996 y el 2014 que incluyeron 8743 individuos infectados por el VIH provenientes de 14 países. La razón de posibilidades agrupada general (OR) para la asociación entre estar empleado y la adherencia a la TAR fue 1,27 (intervalo de confianza del 95%, IC: 1,04–1,55). La asociación fue significativa en los estudios en países con ingresos bajos (OR: 1,85, IC del 95%: 1,58–2,18) ycon ingresos altos (OR: 1,33, IC del 95%: 1,02–1,74), pero no en los países con ingresos medios (OR: 0,94, IC del 95%: 0,62– 1,42). Además, los estudios publicados después de 2011 y los de mayor tamaño mostraron una relación menor entre el empleo y la adherencia que, respectivamente, los estudios anteriores y más pequeños. 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