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Prevalence of depression or depressive symptoms among people living with HIV/AIDS in China: a systematic review and meta-analysis

Prevalence of depression or depressive symptoms among people living with HIV/AIDS in China: a... Background: The number of people living with HIV/AIDS (PLHA) in China continues to increase. Depression, a common mental disorder in this population, may confer a higher likelihood of worse health outcomes. An estimate of the prevalence of this disorder among PLHA is required to guide public health policy, but the published results vary widely and lack accuracy in China. The goal of this study was to estimate the pooled prevalence of depression or depressive symptoms among PLHA in China. Methods: A systematic literature search of several databases was conducted from inception to June 2017, focusing on studies reporting on depression or depressive symptoms among PLHA in China. The risk of bias of individual studies was assessed using a modified version of the Newcastle-Ottawa scale. The overall prevalence estimates were pooled using random-effects meta-analysis. Differences according to study-level characteristics were examined using stratified meta-analysis and meta-regression. Results: Seventy-four observational studies including a total of 20,635 PLHA were included. The pooled prevalence of depression or depressive symptoms was 50.8% (95% CI: 46.0–55.5%) among general PLHA, 43.9% (95% CI: 36.2–51.9%) among HIV-positive men who have sex with men, 85.6% (95% CI: 64.1–95.2%) among HIV-positive former blood/plasma donors, and 51.6% (95% CI: 31.9–70.8%) among other HIV-positive populations. Significant heterogeneity was detected across studies regarding these prevalence estimates. Heterogeneity in the prevalence of depression among the general population of PLHA was partially explained by the geographic location and baseline survey year. Conclusions: Because of the significant heterogeneity detected across studies regarding these prevalence estimates of depression or depressive symptoms, the results must be interpreted with caution. Our findings suggest that the estimates of depression or depressive symptoms among PLHA in China are considerable, which highlights the need to integrate screening and providing treatment for mental disorders in the treatment package offered to PLHA, which would ultimately lead to better health outcomes in PLHA. Keywords: Prevalence, Depression, Depressive symptoms, HIV/AIDS, Systematic review, Meta-analysis * Correspondence: liche4005@126.com; xuanlqx@126.com Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. BMC Psychiatry (2018) 18:160 Page 2 of 14 Background While revealing a high occurrence of depression or de- Human immunodeficiency virus (HIV) infection remains pressive symptoms among PLHA, the results of existing a significant social issue worldwide. Estimates reported studies have been fragmentary and inconsistent. For by the World Health Organization (WHO) suggested example, the prevalence among PLHA in Changsha City that 36.7 million people were living with HIV infection was 18.3% [28], whereas among PLHA in Wuhan City, it and acquired immune deficiency syndrome (AIDS) at was 40.4% [29], among PLHA in Shanghai City, it was the end of 2015, with 2.1 million new infections and 1.1 60.3% [29], and among PLHA in Kunming City, it was million deaths due to HIV-related causes. Most people 81.5% [30]. This knowledge gap is an obstacle to policy living with HIV/AIDS (PLHA) are in low-income and and practice. For example, the success of a screening middle-income countries [1]. As a middle-income coun- program is sensitive to base prevalence. As the inconsist- try, the number of PLHA continues to increase in China, encies are outstanding in the current literature, it would although the nationwide epidemic situation of HIV/ be useful to analyze the data provided in the scientific AIDS remains at a low rate. According to the Chinese literature using integrated approaches to establish the Center for Disease Control and Prevention, there were extent of depression or depressive symptoms among 0.50 million people infected with HIV at the end of 2014 PLHA and clarify the reasons for the differences. in China [2], and in June 2017, this number increased to Therefore, in the present study, the objective was to 0.66 million, 41.7% of whom were AIDS patients [3]. conduct a systematic review and meta-analysis of studies From 2014 to 2016, more than 10,000 people were in- to determine the prevalence of depression or depressive fected with HIV every year [2–4]. symptoms among PLHA in China and to explore the Since the introduction of highly active antiretroviral possible causes of the inconsistencies in the current therapy (ART) in the late 1990s, a large percentage of estimates. individuals with HIV-infection have been able to avoid death and live longer in a healthy condition. Neverthe- Methods less, due to social stigma, sexual dysfunction, long-term Search strategy physical discomfort and illness, side effects of antiretro- Two reviewers independently searched the EMBASE, Web viral therapy, and neurobiological changes [5, 6], PLHA of Science, PubMed, Wanfang, China Biology Medicine are at a higher risk of mental disorders, particularly de- disc, China National Knowledge Infrastructure, and Weipu pression. Evidence suggests that, depression occurs more databases from inception to June 2017 for articles in commonly in HIV-positive individuals, with a prevalence English and Chinese, with no restriction on the year of that is two to four times higher compared with compar- the study.. The following search terms were used: human able HIV-negative individuals or the general population immunodeficiency virus, acquired immune deficiency [7–9]. Individuals with HIV infection and depression syndrome, HIV, AIDS, depression, depressive disorder, perform more poorly on clinical outcomes [10]. In fact, depressive symptom, mental disorder, mental health, evidence suggests that depression may reduce antiretro- mood disorder, affective disorder, psychological health, viral therapy adherence and quality of life, weaken the and psychiatric. Search strategy details are shown in physical function and therapeutic effect [11, 12], and Additional file 1. In addition, the reviewers manually confer a higher rate of medical comorbidities [13, 14]. searched the reference lists of identified articles to identify Moreover, in several studies, depression has been found any relevant studies missed in the initial search. to be associated with higher HIV viral loads and lower CD4 counts, even after controlling for the effects of ad- Study selection herence, which predict a worsening disease progression At the stage of titles and abstracts screening, we purposely and mortality [11, 15–20]. Even depressive symptoms, broadened the inclusion criteria to obtain any relevant which do not necessarily meet the entire diagnostic cri- study. First, studies were considered for inclusion if they teria for a depressive disorder, have been identified as a were published in Chinese or English and reported on de- significant factor associated with worse health outcomes pression or depressive symptoms among PLHA. Then, the among people with HIV infection, including impaired full texts of all selected studies were reviewed. Articles were immunological response and mortality [21–27]. There- included if they 1) were cross-sectional or cohort in design, fore, screening for depression or depressive symptoms is 2) reported PLHA in China as a primary study population, an overriding concern in identifying significant risk fac- 3) used a standard instrument to assess for depression or tors for health outcomes among those who are living depressive symptoms, and 4) provided information about with HIV/AIDS. prevalence estimate of depression or depressive symptoms Given the importance of the association between HIV among PLHA. Conversely, articles were excluded if they 1) infection and depression, scholars have been committed were review papers, conference abstracts, case reports, to the epidemiological study of depression in China. experimental studies, qualitative studies or case-control Wang et al. BMC Psychiatry (2018) 18:160 Page 3 of 14 studies, 2) had incomplete or unclear data, or 3) were heterogeneity, the pooled prevalence estimates and corre- duplicate publications. Studies using only the data ob- sponding 95% confidence intervals (CIs) were calculated tained from the National Health Insurance Research using random-effects meta-analyses. Data from studies Database (NHIRD) were also excluded because of the based on HIV-positive sub-populations with specific char- possibility of underestimation. When there was more acteristics (i.e., men who have sex with men [MSM], preg- than one study involving the same population of PLHA, nant women, tuberculosis [TB] patients, injected drug users only the most recent published or comprehensive one [IDUs] and former blood/plasma donors [FBPD]) were ana- was included. In addition, if the same data were pub- lyzed separately when at least six studies were available. As lished in both Chinese and English, then the articles fewer than six studies reported data on HIV-positive published in Chinese were excluded. pregnant women, HIV-TB co-infected individuals and HIV-positive IDUs, studies on those sub-populations Data extraction were combined as “other HIV-positive population” to Two reviewers independently extracted and evaluated estimate the pooled prevalence. Cochran Q test and the the data for each included article using a self-designed I statistic were used to assess the between-study het- data abstraction form. Disagreements were resolved erogeneity. The Cochran Q test was used to evaluate through discussion or consultation with a third reviewer whether the variation across studies was compatible when consensus could not be achieved. The following with chance, and p < 0.1 was considered to indicate sig- data were extracted: the first author, year of publication, nificant heterogeneity. The I statisticwas aquantita- duration of data collection, geographic location, study tive indicator used to evaluate the percentage of total design, sample source, subjects, sample size, average age variance in prevalence estimates due to statistical het- of participants (mean or median), number and percent- erogeneity rather than chance, or sampling error (I > age of male participants, screening or diagnostic method, 75% indicates high heterogeneity, 51–75% indicates outcome definition (screening instrument cutoff or diag- substantial heterogeneity, 26–50% indicates moderate nostic criteria) and reported prevalence estimates of heterogeneity, and ≤ 25% indicates low heterogeneity). depression or depressive symptoms among PLHA. If a Results from included studies were grouped according to study reported more than one estimate assessed by dif- pre-specified study-level characteristics, and then they were ferent measurement tool, the one detected by the more compared using subgroup meta-analysis (for screening in- valid measurement tool (i.e., the tool with higher specifi- strument cut-off or diagnostic criteria, geographic location, city and sensitivity) was extracted. When there were sample source and total NOS score) or random-effects multiple estimates over time in the same sample of a meta-regression (for baseline survey year, sample size, age study, the first one was chosen. and sex). The difference between subgroups was examined using the Cochran Q test (p < 0.05 indicated statistically Assessment of risk of bias significant differences). To determine the influence of The risk of bias in the included studies was assessed individual studies on the pooled prevalence estimates, using a modified version of the Newcastle-Ottawa scale sensitivity analyses were performed by serially repeating (NOS) which was referred to the version used in the the meta-analysis after the exclusion of each included meta-analysis conducted by Rotenstein et al. to estimate study. If the point estimate of the new pooled preva- the prevalence of depression or depressive symptoms in lence is outside of the 95% confidence interval of the medical students [31]. The tool contained five items, original pooled prevalence, it can be determined that which determine the risk of bias, including sample rep- the study which has been excluded to get the new resentativeness, sample size, response rate, ascertain- prevalence has an significant effect on the original pooled ment of depression, and quality of descriptive statistics prevalence. Publication bias was evaluated using Egger’s reporting (for details, see Additional file 2). The five line regression test (p < 0.05 indicated statistically signifi- criteria were assessed as either “1 point” or “0 point”. cant differences). Preferred Reporting Items for Systematic The higher the score, the lower the risk of bias in an in- Reviews and Meta-analysis guidelines were strictly ad- dividual study. According to Rotenstein et al. [31], a hered to wherever appropriate [32]. study was rated as having a high risk of bias if less than 3 points were given, and a low risk of bias if 3 or more points were given. Results Identification and characteristics of studies Statistical analysis In total, 54,005 unique citations were identified after an All analyses were performed using R version 3.4.1 (R initial search, 53,771 of which were excluded after removing Foundation for Statistical Computing), ‘meta’ package duplicate papers and screening titles and abstracts (Fig. 1). (version 4.8–4). In the presence of between-study Then, the full text of 234 articles were reviewed, 74 of Wang et al. BMC Psychiatry (2018) 18:160 Page 4 of 14 Fig. 1 Flow diagram of included/excluded studies which [9, 28–30, 33–102]were consideredtobeeligible Study quality and included in the systematic review and meta-analysis. Modified NOS score components for all 74 individual In the74studies,there wereatotal of 20,635 PLHA. The studies are shown in Additional file 4 and Additional file 5. median number of participants in those studies was 185 Fifty-seven studies (77.0%) had an overall rating of low (range: 28 to 4103). Sixty-seven studies were conducted in risk, while the rest were rated as high. One-fifth of the one of the seven areas (twenty-one in East China, seventeen studies scored 1 point on each of these five items. The in Central China, ten in South China, nine in Southwest overall sample representativeness was fair, as more than China, six in North China, three in Northeast China and half of the studies (41, 55.4%) sampled PLHA from one in Northwest China), six studies were conducted in HIV-infected individuals databases of the provincial or two or more areas and one study did not report the study municipal Center for Disease Control and Prevention or site. The papers were published between 2004 and 2017, from multiple study sites. Forty-one studies reported re- and more than 70% (54/74 studies) were published between sponses of at least 70%, and of these more than 90% sam- 2011 and 2017. Seventy-one cross-sectional studies pled 100 or more PLHA. (n = 20,154) and three longitudinal studies (n = 481) reported on the prevalence of depression or depressive Depression or depressive symptoms among the general symptoms, and twenty-three of the seventy-three observa- PLHA tional studies focused on specific sub-populations (ten on Estimate of overall prevalence of depression or depressive MSM, seven on FBPD, two on pregnant women, two on symptoms among the general population of PLHA HIV-TB co-infected individuals, and two on IDUs). The prevalence estimates of depression or depressive More details are shown in an additional table file (see symptoms among the general PLHA reported by 50 in- Additional file 3). cluded studies ranged from 18.3 to 86.9%. Meta-analytic Wang et al. BMC Psychiatry (2018) 18:160 Page 5 of 14 pooling of these prevalence estimates yielded a crude and univariate meta-regression analysis were conducted summary prevalence of 50.8% (8023/14,824 individuals, within subgroups of studies using the same instruments 95% CI: 46.0–55.5%), with significant between-study when at least five studies were available. An additional file heterogeneity present (I = 96.4%, p < 0.001) (Fig. 2). shows this process in more detail (see Additional file 7). No evidence of publication bias was detected using No significant differences were observed between the Egger’stest(t = − 1.549, p = 0.128). Sensitivity community-based and hospital-based studies, as well analysis showed that none of the studies had a sig- as studies with total NOS score < 3 points and ≥ 3 nificant influence on the pooled prevalence estimate points, within any instruments. Heterogeneity was par- (see Additional file 6). tially accounted for by geographic location, as studies con- To further characterize the range of prevalence esti- ducted in North China yielded lower depression or mates of depression or depressive symptoms, a stratified depressive symptoms prevalence estimates than studies analysis was conducted, based on the screening instru- conducted in Central China (24.0% [95% CI: 14.2–37.7%] ments and cut-off scores used in these methodologically vs 62.9% [95% CI: 59.0–66.7%]), as well as studies con- diverse studies (Table 1). Summary prevalence estimates ducted in Central China (24.0% [95% CI: 14.2–37.7%] vs of depression or depressive symptoms ranged from 70.0% [95% CI: 63.0–76.2%]) among five studies using 18.3% (95% CI: 13.0–24.8%) for Psychological “Comput- the CES-D-20 with a cutoff score of 16 or greater erized Tomography” 4.0 Vision (PCT V4.0) to 75.0% (see Additional file 7 Table S1). (95% CI: 55.1–89.3%) for the Beck Depression Inventory The baseline survey year significantly contributed to (BDI), with a cut-off score of 10 or greater. The median the observed notable heterogeneity among the studies summary prevalence estimate was 48.2% (95% CI: 43.2– using the Zung Self-Rating Depression Scale (Zung SDS), 53.1%) for the 20-item Center for Epidemiological Stud- with acut-offscoreof50orgreater,and the 90-item Symp- ies Depression Scale (CES-D-20), with a cut-off score of tom Checklist (SCL-90), with a cut-off score of 2 or greater. 17 or greater. Similarly, age also accounted for between-study heterogen- eity within two instruments, Zung SDS score ≥ 50 and Subgroup analysis and meta-regression CES-D-20 score ≥ 16. Sample size also significantly contrib- Statistically significant differences in prevalence estimates uted to the observed notable heterogeneity within three in- were identified among studies conducted in different areas struments (Zung SDS score ≥ 50, SCL-90 score ≥2and (Q = 41.3, p < 0.001). When stratified by the sample CES-D-20 score ≥ 16), although the results were inconsist- source, the pooled prevalence estimates among the PLHA ent (i.e., two analyses suggested that the prevalence es- from the 20 community-based samples (55.3, 95% CI: timate of depression was increasing with sample size, 47.0–63.4%) was comparable to the PLHA from the 30 whileathird onesuggested that it wasdecreasing). studies reporting on hospital-based samples (47.6, 95% CI: Sex and ART did not significantly contribute to the 41.7–53.6%) (Q = 2.2, p = 0.141). Similarly, there were no between-study heterogeneity within any of the four in- significant differences in the prevalence estimates of de- struments (see Additional file 7 Table S2). pression or depressive symptom between studies with total NOS score < 3 points and studies with total ≥ 3 Depression or depressive symptoms in specific PLHA points (Q = 2.5, p = 0.117). Data are shown in Table 2. The overall pooled prevalence of depression or de- The results of the random-effects meta-regression showed pressive symptoms was 43.9% (1171/2785 individuals, that the prevalence estimates of depression or depressive 95% CI: 36.2–51.9%) among HIV-positive MSM, 85.6% symptoms significantly varied with the baseline survey year (941/1233 individuals, 95% CI: 64.1–95.2%) among (slope = − 8.3% per 1-year increase [95% CI: -14.2% to − HIV-positive FBPD, and 51.6% (457/1122 individuals, 2.4%]; Q = 7.5, p = 0.006). but did not significantly vary with 95% CI: 31.9–70.8%) among other HIV-positive popu- thesamplesize(slope=1.5% per 100-individual increase lations. Significant heterogeneity was detected across [95% CI: -2.1 to 5.0%]; Q = 0.7, p = 0.418), mean or median studies in the prevalence estimates of depression or age (slope = 3.9% per 1-year increase [95% CI: -0.1 to 8.8%]; depressive symptoms in thesespecificsub-populations Q=2.5, p = 0.115), sex (slope = − 0.7% per percentage (I range: 93.9–97.8%; all p< 0.05) (Fig. 3). increase in male individuals [95% CI: -2.0 to 0.7%]; Q=1.0, p = 0.323) or antiretroviral therapy (ART) Discussion (slope = − 0.1% per percentage increase in individuals In the present systematic review and meta-analysis, we with ART [95% CI: -0.9 to 0.6%]; Q = 0.1, p = 0.740). quantified the proportion of depression or depressive symptoms among PLHA using data from seventy-four Heterogeneity within the depression survey instruments studies involving 20,635 individuals in seven areas of To identify potential sources of heterogeneity inde- China. On average, the pooled prevalence estimates were pendent of assessment method, stratified meta-analysis 50.8% for depression or depressive symptoms among the Wang et al. BMC Psychiatry (2018) 18:160 Page 6 of 14 Fig. 2 Forest plot of the prevalence of depression or depressive symptoms among the general people living with HIV/AIDS in China. The vertical dotted line indicates the overall effect size of all studies combined. The studies are ordered alphabetically by screening instrument and cutoff score, and then sorted by decreasing publication year within each instrument. BDI, Beck Depression Inventory; CES-D-10, 10-item Center for Epidemiological Studies Depression Scale; CES-D-20, 20-item Center for Epidemiological Studies Depression Scale; HADS-D, Hospital Anxiety and Depression Scale; HAMD-24, 24-item Hamilton Depression Rating Scale; PCT V4.0, Psychological ‘Computerized Tomography’ 4.0 Vision; PHQ-9, 9- item Patient Health Questionnaire; SCID-I, Structured Clinical Interview for the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders Axis I Disorders; SCL-90, 90-item Symptom Check List; Zung-SDS, Zung Self-Rating Depression Scale Wang et al. BMC Psychiatry (2018) 18:160 Page 7 of 14 Table 1 Meta-analyses of the prevalence of depression or depressive symptoms among the general PLHA in China stratified by instrument and cutoff score Screening instrument and cutoff score No. of Studies No. Depressed Total No. Prevalence, % (95% CI) I (%) P value for heterogeneity Beck Depression Inventory Score ≥ 10 1 21 28 75.0 (55.1, 89.3) –– Beck Depression Inventory Score ≥ 16 1 65 145 44.8 (36.6, 53.3) –– Beck Depression Inventory II Score ≥ 11 1 28 41 68.3 (51.9, 81.9) –– Beck Depression Inventory II Score ≥ 14 4 457 920 49.3 (33.2, 65.5) 95.6 < 0.001 10-item Center for Epidemiologic Studies Depression 2 139 268 51.9 (45.9, 57.8) 0 0.426 Scale Score ≥ 10 20-item Center for Epidemiologic Studies Depression 5 1172 1752 60.9 (51.2, 69.8) 91.9 < 0.001 Scale Score ≥ 16 20-item Center for Epidemiologic Studies Depression 1 197 409 48.2 (43.2, 53.1) –– Scale Score ≥ 17 20-item Center for Epidemiologic Studies Depression 1 150 406 36.9 (32.2, 41.8) –– Scale Score ≥ 20 Hospital Anxiety and Depression Scale Score ≥ 8 4 2929 4790 57.6 (36.7, 76.0) 98.6 < 0.001 24-item Hamilton Depression Rating Scale Score ≥ 8 1 38 142 26.8 (20.1, 34.6) –– Psychological “Computerized Tomography”4.0 Vision 1 33 180 18.3 (13.0, 24.8) –– 9-item Patient Health Questionnaire Score ≥ 5 3 594 862 66.4 (46.9, 81.6) 96.5 < 0.001 Patient Health Questionnaire-9 Score ≥ 10 1 149 370 40.3 (35.2, 45.5) –– Structured Clinical Interview for the fourth edition of 1 22 60 36.7 (24.6, 50.1) –– the Diagnostic and Statistical Manual for Mental Disorders Axis I Disorders 90-item Symptom Check List Score ≥ 2 7 532 867 57.4 (42.9, 70.7) 93.4 < 0.001 Zung Self-Rating Depression Scale Score ≥ 50 10 985 2477 44.8 (36.3, 53.6) 93.8 < 0.001 Zung Self-Rating Depression Scale Score ≥ 53 6 512 1107 46.0 (35.0, 57.5) 92.4 < 0.001 PLHA people living with HIV/AIDS general PLHA. We also quantified these proportion [106–110]. Based on a nationally representative sample, among specific PLHA. As significant heterogeneity was it is demonstrated that depression among PLHA is detected across studies for all these prevalence estimates, under-diagnosed in clinical practice in the United States the results must be interpreted with caution. To the best [111]. Although there is no study on this issue in China, of our knowledge, this study represents the first time we can speculate that depression in the Chinese people that the epidemic of depression among PLHA in China with HIV/AIDS is also under-diagnosed in clinical prac- was exhaustively reviewed. As depression among PLHA tice because more than three-quarters of non-psychiatric is a public health issue, the risk of burden on human re- clinicians in China lack adequate knowledge of depres- sources and the health care systems is considerable. The sion [112], which has proven to contribute to the diffi- study could help to estimate the public health burden of culty in identifying individuals with depression [113]. depression among PLHA in China and to guide policy, Moreover, a strong stigma against PLHA lead them to as well as advocacy efforts. Furthermore, the study rep- defer seeking health care services or to disclose their resents the first step in developing effective interven- own HIV status to the health care workers [114], which tions to prevent and treat associated sequelae. is an additional obstacle to early detection and treatment Evidence suggested that the prevalence of depression of depression among PLHA. In fact, the serious shortness among the general population in China ranged between and uneven distribution of mental health resources are 1.2 and 6.9% [103, 104], significantly lower than the obstacles to directing adequate attention toward those prevalence rate reported in our study, which further health issues [115, 116]. To improve the current situation, confirmed that depression was an outcome conforming the National Heath and Family Planning Commission of to logic among PLHA [105]. However, due to the com- the People’s Republic of China issued the Nation Mental mon symptoms associated with HIV illness, such as Health Program (2015–2020) [116] in 2015, in which a pain, fatigue, insomnia, anorexia and cognitive impair- series of specific goals aimed at ultimately promoting ment, it is difficult to diagnose depression among PLHA public mental health have been proposed, including Wang et al. BMC Psychiatry (2018) 18:160 Page 8 of 14 Table 2 Meta-analyses of the prevalence of depression or depressive symptoms among PLHA in China stratified by study-level characteristics Characteristics No. of Studies No. Depressed Total No. Prevalence, % (95% CI) I (%) P value for heterogeneity Test for subgroup differences Q (df) P value Geographic location 41.3 (7) < 0.001 Central China 13 1836 3927 48.8 (40.3, 57.5) 96.3 < 0.001 Cross-region 4 2649 4279 65.7 (58.3, 72.4) 78.8 0.003 East China 14 927 2165 47.4 (38.5, 56.5) 93.3 < 0.001 North China 4 126 345 33.5 (22.9, 46.0) 79.9 0.002 Northeast 3 869 1242 67.8 (60.9, 74.0) 80.1 0.007 Northwest 1 45 103 43.7 (33.9, 53.8) –– South China 7 1019 1831 52.0 (37.2, 66.5) 97.1 < 0.001 Southwest 4 552 932 55.7 (29.1, 79.4) 98.1 < 0.001 Sample source 2.2 (1) 0.141 Community-based 20 2773 4840 55.3 (47.0, 63.4) 96.5 < 0.001 Hospital-based 30 5250 9984 47.6 (41.7, 53.6) 96.3 < 0.001 Total score 2.5 (1) 0.117 < 3 points 12 504 1167 43.8 (34.4, 53.8) 90.2 < 0.001 ≥ 3 points 38 7519 13,657 52.9 (47.5, 58.2) 96.9 < 0.001 PLHA people living with HIV/AIDS Wang et al. BMC Psychiatry (2018) 18:160 Page 9 of 14 Fig. 3 Forest plot of the prevalence of depression or depressive symptoms among the subgroups of people living with HIV/AIDS in China. The vertical dotted lines indicate the overall effect sizes of all studies combined within each sub-population who were living with HIV/AIDS in China. MSM, men who have sex with men; FBPD, former blood/plasma donors general improvement of the public cognition of depression some other studies [53, 58, 73, 121] have found the preva- and other common mental disorders and the public lence to be lower in patients who had received ART than awareness of forwardly seeking medical advice, as well in those who had not, while only one study has reported as obvious improvement in ability of medical workers statistical significance for this opposite result [121]. Due to identify depression. to the lack of data available on depression prevalence In our study, depression was found to be associated estimates among the people using and not using ART, with the baseline survey time, on the decrease over time, stratified meta-analyses could not be conducted in even among some studies using common instruments. these two sub-populations. Instead, random-effects Economic development in the past decades may be a meta-regression analysis was used to explore the rela- possible reason for this decrease in depression preva- tionship between ART and depression or depressive lence, which has greatly increased the investment of symptoms prevalence. As a result, there was no sig- mental health as well as the availability of mental health nificant association between them. services [115]. The growing awareness of AIDS-related Given the higher reported prevalence estimates of knowledge among the public [117, 118] helps to reduce depression among females in the general population, discrimination against PLHA and, hence, may be con- females were considered to be more vulnerable than ductive to decreasing the prevalence of depression. males to the onset of depression [122], a finding sup- Even today, no consensus has been reached on the im- ported by evidence from studies conducted in PLHA pact of ART on depression among PLHA in China. Sev- populations. In a observational cross-sectional study eral studies [54, 61, 68, 72, 78, 119, 120]havereported a conducted in central India recruiting a large sample of higher prevalence of depression or depressive symptoms 1181 PLHA, Deshmukh et al. have found that a greater among PLHA who have undergone ART when compared percentage of females was screened positive for depressive with those who have not, and only two studies have re- symptoms when compared with males (59.9% vs 43.7%, ported a statistical significance [119, 120]. Nevertheless, p<0.001) [123]. In another cross-sectional study Wang et al. BMC Psychiatry (2018) 18:160 Page 10 of 14 conducted in Nigeria, a significantly higher prevalence to an over-estimation of true rates in the meta-analysis with of major depressive disorders was reported among fe- all the included studies relying on screening instruments. males than among males [124]. However, in a current Despite the limitations in self-report inventories of de- study targeted on newly diagnosed HIV-patients, being fe- pressive symptoms, these inventories are still essential male was found to be protective against depression but for assessing depression in HIV-positive individuals without significance (OR = 0.48, p =0.078) [125]. In our because they are easier and more cost-effective for use study, no significant association between the prevalence es- in busy specialty medical clinics and epidemiological timates of depression or depressive symptoms and gender surveys than formal diagnostic interviews [130, 131], was determined. In addition, in the general population, age particularly in epidemiological surveys. Because of the has also been proven to be associated with variations in the high prevalence in China, it is nearly impossible to assess prevalence estimates of depression, with younger partici- depression through formal interviews between psychia- pants having higher prevalence of current and lifetime de- trists and HIV-positive individuals in epidemiological pression than participants older than 50 or 55 years [126]. studies. As an alternative, self-report inventories are the However, the association between age and depression best choice. Nevertheless, for primary care physicians, among PLHA remained unclear. The results showed that a it is better to remember that the diagnosis of depres- younger age was significant associated with the higher sion should not be based solely on the results of the prevalence of depression screened by CES-D-20 [127], screening questionnaire [132]. In this meta-analysis, to as well as diagnoses by psychiatrists, according to control the diversity in these inventories, stratified ana- DSM-IV-TR [128], even after adjusting for confound- lyses were conducted based on survey instrument and ing factors. However, the study conducted in cut-off scores that identified a range of prevalence esti- HIV-infected adults undergoing anti-retroviral treatment mates not presented in the previous review [133]. demonstrated that participants older than 50 years old had This study has important limitations. As with other a two times higher risk of depression when compared with meta-analyses, significant heterogeneity was found in the participants with between 18 and 30 years old [129]. In prevalence estimates in our study, which was incom- addition, the result from the study which used the Depres- pletely explained by the stratified meta-analyses and sion, Anxiety, Stress subscales, and full Scale (DASS-21) meta-regressions analyses. We hypothesize that other for depression screening showed that no significant ef- variables might affect the heterogeneity, such as poor in- fect of age on the rate of depression was found among come adequacy, unemployment, homeless, lower CD4 PHLA [123]. In this meta-analysis, although no signifi- counts, higher viral loads, the severity of depressive cant association was found between age and the pooled symptoms, duration of HIV/AIDS, poor self-efficacy and prevalence of depression, age was demonstrated to be lack of social support. However, we were unable to ob- linked with a higher risk of depression in studies with tain adequate information about these variables. For Zung SDS scores ≥50 or CES-D-20 scores ≥16 as the cri- example, less than 1/3 of the studies reported the teria for screening positive, which might support the posi- average or median counts of CD4 cells among HIV in- tive association between age and depression among PLHA fected populations, and fewer than 10 studies provided to some extent. However, as there were few studies using employment-specific prevalence estimates of depres- those two screening instrument cut-offs as screening cri- sion. In addition, although an extensive document re- teria, the results must be interpreted with caution. Further trieve was performed in multiple databases, the studies are needed to clarify the associations between gen- existence of non-indexed studies in those databases der/age and the risk of depression among PLHA, which might have led to some relevant studies being ignored. will help to identify individuals in high-risk. Moreover, although an attempt was made to minimize When interpreting the results of this study, note that the the possible bias in the process of document retrieving data synthesized in this meta-analysis were nearly entirely with specific searches in major English-Chinese data- extract from studies using self-report inventories of depres- bases (including master and doctoral theses), there sive symptoms as the survey instruments, which had a wide may still be some unidentified papers. Fortunately, as range of sensitivity and specificity for diagnosing major the results of Egger’s test results showed, there was no depressive disorder (Additional file 4). Instruments such as publication bias found in all results because we ob- the Psychological “Computerized Tomography” 4.0 Vision tained a certain percentage of data from unpublished (PCT V4.0) have high specificity and sensitivity for papers (fourteen theses [38, 56, 57, 66, 70, 71, 75, 82, diagnosing depression, whereas others instruments, 87, 89, 91, 94, 96, 99]). such as the SCL-90, have low specificity and should be regarded as screening tools. Furthermore, evidences Conclusions suggest that screening tools tend to over-estimate Our findings suggest that the estimates of depression prevalence relative to diagnostic tools, which may lead or depressive symptoms among PLHA in China are Wang et al. BMC Psychiatry (2018) 18:160 Page 11 of 14 considerable. Given that the progression of depression Competing interests The authors declare that they have no competing interests. are associated with a higher short-term suicide risk and a higher long-term risk of cardiovascular disease and cancer [134, 135], the findings in this study highlight Publisher’sNote the need for screening and treatment for mental disor- Springer Nature remains neutral with regard to jurisdictional claims in ders to be integrated in the treatment package offered published maps and institutional affiliations. to PLHA, which will ultimately lead to better health Author details outcomes for PLHA [136]. 1 Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China. Department of Mathematics, Mzuzu University, Mzuzu 2, Malawi. Additional files Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China. Department of Medical Psychology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Additional file 1: “Search strategy used in the current systematic review Province, China. and meta-analysis”. (DOC 66 kb) Additional file 2: “Modified Newcastle-Ottawa risk of bias scoring Received: 23 January 2018 Accepted: 11 May 2018 guide”. (DOC 27 kb) Additional file 3: “Selected characteristics of the 74 studies on the prevalence of depression or depressive symptoms among people living with HIV/AIDS in China”. (DOC 146 kb) References 1. World Health Organization. 10 facts on HIV/AIDS. 2017. http://www.who.int/ Additional file 4: “Modified Newcastle-Ottawa risk of bias score for the 74 features/factfiles/hiv/en/. Accessed 16 Sept 2017 studies included in this systematic review and meta-analysis”.(DOC 190 kb) 2. Chinese Center for Disease Control and Prevention. 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We thank all our colleagues working in Department of Epidemiology and Psychiatric correlates of HAART utilization and viral load among HIV-positive Health Statistics, Xiangya School of public health of Central South University, impoverished persons. AIDS. 2011;25:1113–8. Dr. Li working in Department of Oncology, Xiangya Hospital of Central South 12. Sumari-de Boer IM, Sprangers MA, Prins JM, Nieuwkerk PT. HIV stigma and University and Dr. Guo working in Department of Medical Psychology, the depressive symptoms are related to adherence and virological response to Second Xiangya Hospital of Central South University. antiretroviral treatment among immigrant and indigenous HIV infected patients. AIDS Behav. 2012;16:1681–9. Availability of data and materials 13. Sabin CA, Ryom L, De Wit S, Mocroft A, Phillips AN, Worm SW, et al. 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Gen Hosp Psychiatry. 2015;37:277–82. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Psychiatry Springer Journals

Prevalence of depression or depressive symptoms among people living with HIV/AIDS in China: a systematic review and meta-analysis

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Copyright © 2018 by The Author(s).
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Medicine & Public Health; Psychiatry; Psychotherapy
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10.1186/s12888-018-1741-8
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Abstract

Background: The number of people living with HIV/AIDS (PLHA) in China continues to increase. Depression, a common mental disorder in this population, may confer a higher likelihood of worse health outcomes. An estimate of the prevalence of this disorder among PLHA is required to guide public health policy, but the published results vary widely and lack accuracy in China. The goal of this study was to estimate the pooled prevalence of depression or depressive symptoms among PLHA in China. Methods: A systematic literature search of several databases was conducted from inception to June 2017, focusing on studies reporting on depression or depressive symptoms among PLHA in China. The risk of bias of individual studies was assessed using a modified version of the Newcastle-Ottawa scale. The overall prevalence estimates were pooled using random-effects meta-analysis. Differences according to study-level characteristics were examined using stratified meta-analysis and meta-regression. Results: Seventy-four observational studies including a total of 20,635 PLHA were included. The pooled prevalence of depression or depressive symptoms was 50.8% (95% CI: 46.0–55.5%) among general PLHA, 43.9% (95% CI: 36.2–51.9%) among HIV-positive men who have sex with men, 85.6% (95% CI: 64.1–95.2%) among HIV-positive former blood/plasma donors, and 51.6% (95% CI: 31.9–70.8%) among other HIV-positive populations. Significant heterogeneity was detected across studies regarding these prevalence estimates. Heterogeneity in the prevalence of depression among the general population of PLHA was partially explained by the geographic location and baseline survey year. Conclusions: Because of the significant heterogeneity detected across studies regarding these prevalence estimates of depression or depressive symptoms, the results must be interpreted with caution. Our findings suggest that the estimates of depression or depressive symptoms among PLHA in China are considerable, which highlights the need to integrate screening and providing treatment for mental disorders in the treatment package offered to PLHA, which would ultimately lead to better health outcomes in PLHA. Keywords: Prevalence, Depression, Depressive symptoms, HIV/AIDS, Systematic review, Meta-analysis * Correspondence: liche4005@126.com; xuanlqx@126.com Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. BMC Psychiatry (2018) 18:160 Page 2 of 14 Background While revealing a high occurrence of depression or de- Human immunodeficiency virus (HIV) infection remains pressive symptoms among PLHA, the results of existing a significant social issue worldwide. Estimates reported studies have been fragmentary and inconsistent. For by the World Health Organization (WHO) suggested example, the prevalence among PLHA in Changsha City that 36.7 million people were living with HIV infection was 18.3% [28], whereas among PLHA in Wuhan City, it and acquired immune deficiency syndrome (AIDS) at was 40.4% [29], among PLHA in Shanghai City, it was the end of 2015, with 2.1 million new infections and 1.1 60.3% [29], and among PLHA in Kunming City, it was million deaths due to HIV-related causes. Most people 81.5% [30]. This knowledge gap is an obstacle to policy living with HIV/AIDS (PLHA) are in low-income and and practice. For example, the success of a screening middle-income countries [1]. As a middle-income coun- program is sensitive to base prevalence. As the inconsist- try, the number of PLHA continues to increase in China, encies are outstanding in the current literature, it would although the nationwide epidemic situation of HIV/ be useful to analyze the data provided in the scientific AIDS remains at a low rate. According to the Chinese literature using integrated approaches to establish the Center for Disease Control and Prevention, there were extent of depression or depressive symptoms among 0.50 million people infected with HIV at the end of 2014 PLHA and clarify the reasons for the differences. in China [2], and in June 2017, this number increased to Therefore, in the present study, the objective was to 0.66 million, 41.7% of whom were AIDS patients [3]. conduct a systematic review and meta-analysis of studies From 2014 to 2016, more than 10,000 people were in- to determine the prevalence of depression or depressive fected with HIV every year [2–4]. symptoms among PLHA in China and to explore the Since the introduction of highly active antiretroviral possible causes of the inconsistencies in the current therapy (ART) in the late 1990s, a large percentage of estimates. individuals with HIV-infection have been able to avoid death and live longer in a healthy condition. Neverthe- Methods less, due to social stigma, sexual dysfunction, long-term Search strategy physical discomfort and illness, side effects of antiretro- Two reviewers independently searched the EMBASE, Web viral therapy, and neurobiological changes [5, 6], PLHA of Science, PubMed, Wanfang, China Biology Medicine are at a higher risk of mental disorders, particularly de- disc, China National Knowledge Infrastructure, and Weipu pression. Evidence suggests that, depression occurs more databases from inception to June 2017 for articles in commonly in HIV-positive individuals, with a prevalence English and Chinese, with no restriction on the year of that is two to four times higher compared with compar- the study.. The following search terms were used: human able HIV-negative individuals or the general population immunodeficiency virus, acquired immune deficiency [7–9]. Individuals with HIV infection and depression syndrome, HIV, AIDS, depression, depressive disorder, perform more poorly on clinical outcomes [10]. In fact, depressive symptom, mental disorder, mental health, evidence suggests that depression may reduce antiretro- mood disorder, affective disorder, psychological health, viral therapy adherence and quality of life, weaken the and psychiatric. Search strategy details are shown in physical function and therapeutic effect [11, 12], and Additional file 1. In addition, the reviewers manually confer a higher rate of medical comorbidities [13, 14]. searched the reference lists of identified articles to identify Moreover, in several studies, depression has been found any relevant studies missed in the initial search. to be associated with higher HIV viral loads and lower CD4 counts, even after controlling for the effects of ad- Study selection herence, which predict a worsening disease progression At the stage of titles and abstracts screening, we purposely and mortality [11, 15–20]. Even depressive symptoms, broadened the inclusion criteria to obtain any relevant which do not necessarily meet the entire diagnostic cri- study. First, studies were considered for inclusion if they teria for a depressive disorder, have been identified as a were published in Chinese or English and reported on de- significant factor associated with worse health outcomes pression or depressive symptoms among PLHA. Then, the among people with HIV infection, including impaired full texts of all selected studies were reviewed. Articles were immunological response and mortality [21–27]. There- included if they 1) were cross-sectional or cohort in design, fore, screening for depression or depressive symptoms is 2) reported PLHA in China as a primary study population, an overriding concern in identifying significant risk fac- 3) used a standard instrument to assess for depression or tors for health outcomes among those who are living depressive symptoms, and 4) provided information about with HIV/AIDS. prevalence estimate of depression or depressive symptoms Given the importance of the association between HIV among PLHA. Conversely, articles were excluded if they 1) infection and depression, scholars have been committed were review papers, conference abstracts, case reports, to the epidemiological study of depression in China. experimental studies, qualitative studies or case-control Wang et al. BMC Psychiatry (2018) 18:160 Page 3 of 14 studies, 2) had incomplete or unclear data, or 3) were heterogeneity, the pooled prevalence estimates and corre- duplicate publications. Studies using only the data ob- sponding 95% confidence intervals (CIs) were calculated tained from the National Health Insurance Research using random-effects meta-analyses. Data from studies Database (NHIRD) were also excluded because of the based on HIV-positive sub-populations with specific char- possibility of underestimation. When there was more acteristics (i.e., men who have sex with men [MSM], preg- than one study involving the same population of PLHA, nant women, tuberculosis [TB] patients, injected drug users only the most recent published or comprehensive one [IDUs] and former blood/plasma donors [FBPD]) were ana- was included. In addition, if the same data were pub- lyzed separately when at least six studies were available. As lished in both Chinese and English, then the articles fewer than six studies reported data on HIV-positive published in Chinese were excluded. pregnant women, HIV-TB co-infected individuals and HIV-positive IDUs, studies on those sub-populations Data extraction were combined as “other HIV-positive population” to Two reviewers independently extracted and evaluated estimate the pooled prevalence. Cochran Q test and the the data for each included article using a self-designed I statistic were used to assess the between-study het- data abstraction form. Disagreements were resolved erogeneity. The Cochran Q test was used to evaluate through discussion or consultation with a third reviewer whether the variation across studies was compatible when consensus could not be achieved. The following with chance, and p < 0.1 was considered to indicate sig- data were extracted: the first author, year of publication, nificant heterogeneity. The I statisticwas aquantita- duration of data collection, geographic location, study tive indicator used to evaluate the percentage of total design, sample source, subjects, sample size, average age variance in prevalence estimates due to statistical het- of participants (mean or median), number and percent- erogeneity rather than chance, or sampling error (I > age of male participants, screening or diagnostic method, 75% indicates high heterogeneity, 51–75% indicates outcome definition (screening instrument cutoff or diag- substantial heterogeneity, 26–50% indicates moderate nostic criteria) and reported prevalence estimates of heterogeneity, and ≤ 25% indicates low heterogeneity). depression or depressive symptoms among PLHA. If a Results from included studies were grouped according to study reported more than one estimate assessed by dif- pre-specified study-level characteristics, and then they were ferent measurement tool, the one detected by the more compared using subgroup meta-analysis (for screening in- valid measurement tool (i.e., the tool with higher specifi- strument cut-off or diagnostic criteria, geographic location, city and sensitivity) was extracted. When there were sample source and total NOS score) or random-effects multiple estimates over time in the same sample of a meta-regression (for baseline survey year, sample size, age study, the first one was chosen. and sex). The difference between subgroups was examined using the Cochran Q test (p < 0.05 indicated statistically Assessment of risk of bias significant differences). To determine the influence of The risk of bias in the included studies was assessed individual studies on the pooled prevalence estimates, using a modified version of the Newcastle-Ottawa scale sensitivity analyses were performed by serially repeating (NOS) which was referred to the version used in the the meta-analysis after the exclusion of each included meta-analysis conducted by Rotenstein et al. to estimate study. If the point estimate of the new pooled preva- the prevalence of depression or depressive symptoms in lence is outside of the 95% confidence interval of the medical students [31]. The tool contained five items, original pooled prevalence, it can be determined that which determine the risk of bias, including sample rep- the study which has been excluded to get the new resentativeness, sample size, response rate, ascertain- prevalence has an significant effect on the original pooled ment of depression, and quality of descriptive statistics prevalence. Publication bias was evaluated using Egger’s reporting (for details, see Additional file 2). The five line regression test (p < 0.05 indicated statistically signifi- criteria were assessed as either “1 point” or “0 point”. cant differences). Preferred Reporting Items for Systematic The higher the score, the lower the risk of bias in an in- Reviews and Meta-analysis guidelines were strictly ad- dividual study. According to Rotenstein et al. [31], a hered to wherever appropriate [32]. study was rated as having a high risk of bias if less than 3 points were given, and a low risk of bias if 3 or more points were given. Results Identification and characteristics of studies Statistical analysis In total, 54,005 unique citations were identified after an All analyses were performed using R version 3.4.1 (R initial search, 53,771 of which were excluded after removing Foundation for Statistical Computing), ‘meta’ package duplicate papers and screening titles and abstracts (Fig. 1). (version 4.8–4). In the presence of between-study Then, the full text of 234 articles were reviewed, 74 of Wang et al. BMC Psychiatry (2018) 18:160 Page 4 of 14 Fig. 1 Flow diagram of included/excluded studies which [9, 28–30, 33–102]were consideredtobeeligible Study quality and included in the systematic review and meta-analysis. Modified NOS score components for all 74 individual In the74studies,there wereatotal of 20,635 PLHA. The studies are shown in Additional file 4 and Additional file 5. median number of participants in those studies was 185 Fifty-seven studies (77.0%) had an overall rating of low (range: 28 to 4103). Sixty-seven studies were conducted in risk, while the rest were rated as high. One-fifth of the one of the seven areas (twenty-one in East China, seventeen studies scored 1 point on each of these five items. The in Central China, ten in South China, nine in Southwest overall sample representativeness was fair, as more than China, six in North China, three in Northeast China and half of the studies (41, 55.4%) sampled PLHA from one in Northwest China), six studies were conducted in HIV-infected individuals databases of the provincial or two or more areas and one study did not report the study municipal Center for Disease Control and Prevention or site. The papers were published between 2004 and 2017, from multiple study sites. Forty-one studies reported re- and more than 70% (54/74 studies) were published between sponses of at least 70%, and of these more than 90% sam- 2011 and 2017. Seventy-one cross-sectional studies pled 100 or more PLHA. (n = 20,154) and three longitudinal studies (n = 481) reported on the prevalence of depression or depressive Depression or depressive symptoms among the general symptoms, and twenty-three of the seventy-three observa- PLHA tional studies focused on specific sub-populations (ten on Estimate of overall prevalence of depression or depressive MSM, seven on FBPD, two on pregnant women, two on symptoms among the general population of PLHA HIV-TB co-infected individuals, and two on IDUs). The prevalence estimates of depression or depressive More details are shown in an additional table file (see symptoms among the general PLHA reported by 50 in- Additional file 3). cluded studies ranged from 18.3 to 86.9%. Meta-analytic Wang et al. BMC Psychiatry (2018) 18:160 Page 5 of 14 pooling of these prevalence estimates yielded a crude and univariate meta-regression analysis were conducted summary prevalence of 50.8% (8023/14,824 individuals, within subgroups of studies using the same instruments 95% CI: 46.0–55.5%), with significant between-study when at least five studies were available. An additional file heterogeneity present (I = 96.4%, p < 0.001) (Fig. 2). shows this process in more detail (see Additional file 7). No evidence of publication bias was detected using No significant differences were observed between the Egger’stest(t = − 1.549, p = 0.128). Sensitivity community-based and hospital-based studies, as well analysis showed that none of the studies had a sig- as studies with total NOS score < 3 points and ≥ 3 nificant influence on the pooled prevalence estimate points, within any instruments. Heterogeneity was par- (see Additional file 6). tially accounted for by geographic location, as studies con- To further characterize the range of prevalence esti- ducted in North China yielded lower depression or mates of depression or depressive symptoms, a stratified depressive symptoms prevalence estimates than studies analysis was conducted, based on the screening instru- conducted in Central China (24.0% [95% CI: 14.2–37.7%] ments and cut-off scores used in these methodologically vs 62.9% [95% CI: 59.0–66.7%]), as well as studies con- diverse studies (Table 1). Summary prevalence estimates ducted in Central China (24.0% [95% CI: 14.2–37.7%] vs of depression or depressive symptoms ranged from 70.0% [95% CI: 63.0–76.2%]) among five studies using 18.3% (95% CI: 13.0–24.8%) for Psychological “Comput- the CES-D-20 with a cutoff score of 16 or greater erized Tomography” 4.0 Vision (PCT V4.0) to 75.0% (see Additional file 7 Table S1). (95% CI: 55.1–89.3%) for the Beck Depression Inventory The baseline survey year significantly contributed to (BDI), with a cut-off score of 10 or greater. The median the observed notable heterogeneity among the studies summary prevalence estimate was 48.2% (95% CI: 43.2– using the Zung Self-Rating Depression Scale (Zung SDS), 53.1%) for the 20-item Center for Epidemiological Stud- with acut-offscoreof50orgreater,and the 90-item Symp- ies Depression Scale (CES-D-20), with a cut-off score of tom Checklist (SCL-90), with a cut-off score of 2 or greater. 17 or greater. Similarly, age also accounted for between-study heterogen- eity within two instruments, Zung SDS score ≥ 50 and Subgroup analysis and meta-regression CES-D-20 score ≥ 16. Sample size also significantly contrib- Statistically significant differences in prevalence estimates uted to the observed notable heterogeneity within three in- were identified among studies conducted in different areas struments (Zung SDS score ≥ 50, SCL-90 score ≥2and (Q = 41.3, p < 0.001). When stratified by the sample CES-D-20 score ≥ 16), although the results were inconsist- source, the pooled prevalence estimates among the PLHA ent (i.e., two analyses suggested that the prevalence es- from the 20 community-based samples (55.3, 95% CI: timate of depression was increasing with sample size, 47.0–63.4%) was comparable to the PLHA from the 30 whileathird onesuggested that it wasdecreasing). studies reporting on hospital-based samples (47.6, 95% CI: Sex and ART did not significantly contribute to the 41.7–53.6%) (Q = 2.2, p = 0.141). Similarly, there were no between-study heterogeneity within any of the four in- significant differences in the prevalence estimates of de- struments (see Additional file 7 Table S2). pression or depressive symptom between studies with total NOS score < 3 points and studies with total ≥ 3 Depression or depressive symptoms in specific PLHA points (Q = 2.5, p = 0.117). Data are shown in Table 2. The overall pooled prevalence of depression or de- The results of the random-effects meta-regression showed pressive symptoms was 43.9% (1171/2785 individuals, that the prevalence estimates of depression or depressive 95% CI: 36.2–51.9%) among HIV-positive MSM, 85.6% symptoms significantly varied with the baseline survey year (941/1233 individuals, 95% CI: 64.1–95.2%) among (slope = − 8.3% per 1-year increase [95% CI: -14.2% to − HIV-positive FBPD, and 51.6% (457/1122 individuals, 2.4%]; Q = 7.5, p = 0.006). but did not significantly vary with 95% CI: 31.9–70.8%) among other HIV-positive popu- thesamplesize(slope=1.5% per 100-individual increase lations. Significant heterogeneity was detected across [95% CI: -2.1 to 5.0%]; Q = 0.7, p = 0.418), mean or median studies in the prevalence estimates of depression or age (slope = 3.9% per 1-year increase [95% CI: -0.1 to 8.8%]; depressive symptoms in thesespecificsub-populations Q=2.5, p = 0.115), sex (slope = − 0.7% per percentage (I range: 93.9–97.8%; all p< 0.05) (Fig. 3). increase in male individuals [95% CI: -2.0 to 0.7%]; Q=1.0, p = 0.323) or antiretroviral therapy (ART) Discussion (slope = − 0.1% per percentage increase in individuals In the present systematic review and meta-analysis, we with ART [95% CI: -0.9 to 0.6%]; Q = 0.1, p = 0.740). quantified the proportion of depression or depressive symptoms among PLHA using data from seventy-four Heterogeneity within the depression survey instruments studies involving 20,635 individuals in seven areas of To identify potential sources of heterogeneity inde- China. On average, the pooled prevalence estimates were pendent of assessment method, stratified meta-analysis 50.8% for depression or depressive symptoms among the Wang et al. BMC Psychiatry (2018) 18:160 Page 6 of 14 Fig. 2 Forest plot of the prevalence of depression or depressive symptoms among the general people living with HIV/AIDS in China. The vertical dotted line indicates the overall effect size of all studies combined. The studies are ordered alphabetically by screening instrument and cutoff score, and then sorted by decreasing publication year within each instrument. BDI, Beck Depression Inventory; CES-D-10, 10-item Center for Epidemiological Studies Depression Scale; CES-D-20, 20-item Center for Epidemiological Studies Depression Scale; HADS-D, Hospital Anxiety and Depression Scale; HAMD-24, 24-item Hamilton Depression Rating Scale; PCT V4.0, Psychological ‘Computerized Tomography’ 4.0 Vision; PHQ-9, 9- item Patient Health Questionnaire; SCID-I, Structured Clinical Interview for the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders Axis I Disorders; SCL-90, 90-item Symptom Check List; Zung-SDS, Zung Self-Rating Depression Scale Wang et al. BMC Psychiatry (2018) 18:160 Page 7 of 14 Table 1 Meta-analyses of the prevalence of depression or depressive symptoms among the general PLHA in China stratified by instrument and cutoff score Screening instrument and cutoff score No. of Studies No. Depressed Total No. Prevalence, % (95% CI) I (%) P value for heterogeneity Beck Depression Inventory Score ≥ 10 1 21 28 75.0 (55.1, 89.3) –– Beck Depression Inventory Score ≥ 16 1 65 145 44.8 (36.6, 53.3) –– Beck Depression Inventory II Score ≥ 11 1 28 41 68.3 (51.9, 81.9) –– Beck Depression Inventory II Score ≥ 14 4 457 920 49.3 (33.2, 65.5) 95.6 < 0.001 10-item Center for Epidemiologic Studies Depression 2 139 268 51.9 (45.9, 57.8) 0 0.426 Scale Score ≥ 10 20-item Center for Epidemiologic Studies Depression 5 1172 1752 60.9 (51.2, 69.8) 91.9 < 0.001 Scale Score ≥ 16 20-item Center for Epidemiologic Studies Depression 1 197 409 48.2 (43.2, 53.1) –– Scale Score ≥ 17 20-item Center for Epidemiologic Studies Depression 1 150 406 36.9 (32.2, 41.8) –– Scale Score ≥ 20 Hospital Anxiety and Depression Scale Score ≥ 8 4 2929 4790 57.6 (36.7, 76.0) 98.6 < 0.001 24-item Hamilton Depression Rating Scale Score ≥ 8 1 38 142 26.8 (20.1, 34.6) –– Psychological “Computerized Tomography”4.0 Vision 1 33 180 18.3 (13.0, 24.8) –– 9-item Patient Health Questionnaire Score ≥ 5 3 594 862 66.4 (46.9, 81.6) 96.5 < 0.001 Patient Health Questionnaire-9 Score ≥ 10 1 149 370 40.3 (35.2, 45.5) –– Structured Clinical Interview for the fourth edition of 1 22 60 36.7 (24.6, 50.1) –– the Diagnostic and Statistical Manual for Mental Disorders Axis I Disorders 90-item Symptom Check List Score ≥ 2 7 532 867 57.4 (42.9, 70.7) 93.4 < 0.001 Zung Self-Rating Depression Scale Score ≥ 50 10 985 2477 44.8 (36.3, 53.6) 93.8 < 0.001 Zung Self-Rating Depression Scale Score ≥ 53 6 512 1107 46.0 (35.0, 57.5) 92.4 < 0.001 PLHA people living with HIV/AIDS general PLHA. We also quantified these proportion [106–110]. Based on a nationally representative sample, among specific PLHA. As significant heterogeneity was it is demonstrated that depression among PLHA is detected across studies for all these prevalence estimates, under-diagnosed in clinical practice in the United States the results must be interpreted with caution. To the best [111]. Although there is no study on this issue in China, of our knowledge, this study represents the first time we can speculate that depression in the Chinese people that the epidemic of depression among PLHA in China with HIV/AIDS is also under-diagnosed in clinical prac- was exhaustively reviewed. As depression among PLHA tice because more than three-quarters of non-psychiatric is a public health issue, the risk of burden on human re- clinicians in China lack adequate knowledge of depres- sources and the health care systems is considerable. The sion [112], which has proven to contribute to the diffi- study could help to estimate the public health burden of culty in identifying individuals with depression [113]. depression among PLHA in China and to guide policy, Moreover, a strong stigma against PLHA lead them to as well as advocacy efforts. Furthermore, the study rep- defer seeking health care services or to disclose their resents the first step in developing effective interven- own HIV status to the health care workers [114], which tions to prevent and treat associated sequelae. is an additional obstacle to early detection and treatment Evidence suggested that the prevalence of depression of depression among PLHA. In fact, the serious shortness among the general population in China ranged between and uneven distribution of mental health resources are 1.2 and 6.9% [103, 104], significantly lower than the obstacles to directing adequate attention toward those prevalence rate reported in our study, which further health issues [115, 116]. To improve the current situation, confirmed that depression was an outcome conforming the National Heath and Family Planning Commission of to logic among PLHA [105]. However, due to the com- the People’s Republic of China issued the Nation Mental mon symptoms associated with HIV illness, such as Health Program (2015–2020) [116] in 2015, in which a pain, fatigue, insomnia, anorexia and cognitive impair- series of specific goals aimed at ultimately promoting ment, it is difficult to diagnose depression among PLHA public mental health have been proposed, including Wang et al. BMC Psychiatry (2018) 18:160 Page 8 of 14 Table 2 Meta-analyses of the prevalence of depression or depressive symptoms among PLHA in China stratified by study-level characteristics Characteristics No. of Studies No. Depressed Total No. Prevalence, % (95% CI) I (%) P value for heterogeneity Test for subgroup differences Q (df) P value Geographic location 41.3 (7) < 0.001 Central China 13 1836 3927 48.8 (40.3, 57.5) 96.3 < 0.001 Cross-region 4 2649 4279 65.7 (58.3, 72.4) 78.8 0.003 East China 14 927 2165 47.4 (38.5, 56.5) 93.3 < 0.001 North China 4 126 345 33.5 (22.9, 46.0) 79.9 0.002 Northeast 3 869 1242 67.8 (60.9, 74.0) 80.1 0.007 Northwest 1 45 103 43.7 (33.9, 53.8) –– South China 7 1019 1831 52.0 (37.2, 66.5) 97.1 < 0.001 Southwest 4 552 932 55.7 (29.1, 79.4) 98.1 < 0.001 Sample source 2.2 (1) 0.141 Community-based 20 2773 4840 55.3 (47.0, 63.4) 96.5 < 0.001 Hospital-based 30 5250 9984 47.6 (41.7, 53.6) 96.3 < 0.001 Total score 2.5 (1) 0.117 < 3 points 12 504 1167 43.8 (34.4, 53.8) 90.2 < 0.001 ≥ 3 points 38 7519 13,657 52.9 (47.5, 58.2) 96.9 < 0.001 PLHA people living with HIV/AIDS Wang et al. BMC Psychiatry (2018) 18:160 Page 9 of 14 Fig. 3 Forest plot of the prevalence of depression or depressive symptoms among the subgroups of people living with HIV/AIDS in China. The vertical dotted lines indicate the overall effect sizes of all studies combined within each sub-population who were living with HIV/AIDS in China. MSM, men who have sex with men; FBPD, former blood/plasma donors general improvement of the public cognition of depression some other studies [53, 58, 73, 121] have found the preva- and other common mental disorders and the public lence to be lower in patients who had received ART than awareness of forwardly seeking medical advice, as well in those who had not, while only one study has reported as obvious improvement in ability of medical workers statistical significance for this opposite result [121]. Due to identify depression. to the lack of data available on depression prevalence In our study, depression was found to be associated estimates among the people using and not using ART, with the baseline survey time, on the decrease over time, stratified meta-analyses could not be conducted in even among some studies using common instruments. these two sub-populations. Instead, random-effects Economic development in the past decades may be a meta-regression analysis was used to explore the rela- possible reason for this decrease in depression preva- tionship between ART and depression or depressive lence, which has greatly increased the investment of symptoms prevalence. As a result, there was no sig- mental health as well as the availability of mental health nificant association between them. services [115]. The growing awareness of AIDS-related Given the higher reported prevalence estimates of knowledge among the public [117, 118] helps to reduce depression among females in the general population, discrimination against PLHA and, hence, may be con- females were considered to be more vulnerable than ductive to decreasing the prevalence of depression. males to the onset of depression [122], a finding sup- Even today, no consensus has been reached on the im- ported by evidence from studies conducted in PLHA pact of ART on depression among PLHA in China. Sev- populations. In a observational cross-sectional study eral studies [54, 61, 68, 72, 78, 119, 120]havereported a conducted in central India recruiting a large sample of higher prevalence of depression or depressive symptoms 1181 PLHA, Deshmukh et al. have found that a greater among PLHA who have undergone ART when compared percentage of females was screened positive for depressive with those who have not, and only two studies have re- symptoms when compared with males (59.9% vs 43.7%, ported a statistical significance [119, 120]. Nevertheless, p<0.001) [123]. In another cross-sectional study Wang et al. BMC Psychiatry (2018) 18:160 Page 10 of 14 conducted in Nigeria, a significantly higher prevalence to an over-estimation of true rates in the meta-analysis with of major depressive disorders was reported among fe- all the included studies relying on screening instruments. males than among males [124]. However, in a current Despite the limitations in self-report inventories of de- study targeted on newly diagnosed HIV-patients, being fe- pressive symptoms, these inventories are still essential male was found to be protective against depression but for assessing depression in HIV-positive individuals without significance (OR = 0.48, p =0.078) [125]. In our because they are easier and more cost-effective for use study, no significant association between the prevalence es- in busy specialty medical clinics and epidemiological timates of depression or depressive symptoms and gender surveys than formal diagnostic interviews [130, 131], was determined. In addition, in the general population, age particularly in epidemiological surveys. Because of the has also been proven to be associated with variations in the high prevalence in China, it is nearly impossible to assess prevalence estimates of depression, with younger partici- depression through formal interviews between psychia- pants having higher prevalence of current and lifetime de- trists and HIV-positive individuals in epidemiological pression than participants older than 50 or 55 years [126]. studies. As an alternative, self-report inventories are the However, the association between age and depression best choice. Nevertheless, for primary care physicians, among PLHA remained unclear. The results showed that a it is better to remember that the diagnosis of depres- younger age was significant associated with the higher sion should not be based solely on the results of the prevalence of depression screened by CES-D-20 [127], screening questionnaire [132]. In this meta-analysis, to as well as diagnoses by psychiatrists, according to control the diversity in these inventories, stratified ana- DSM-IV-TR [128], even after adjusting for confound- lyses were conducted based on survey instrument and ing factors. However, the study conducted in cut-off scores that identified a range of prevalence esti- HIV-infected adults undergoing anti-retroviral treatment mates not presented in the previous review [133]. demonstrated that participants older than 50 years old had This study has important limitations. As with other a two times higher risk of depression when compared with meta-analyses, significant heterogeneity was found in the participants with between 18 and 30 years old [129]. In prevalence estimates in our study, which was incom- addition, the result from the study which used the Depres- pletely explained by the stratified meta-analyses and sion, Anxiety, Stress subscales, and full Scale (DASS-21) meta-regressions analyses. We hypothesize that other for depression screening showed that no significant ef- variables might affect the heterogeneity, such as poor in- fect of age on the rate of depression was found among come adequacy, unemployment, homeless, lower CD4 PHLA [123]. In this meta-analysis, although no signifi- counts, higher viral loads, the severity of depressive cant association was found between age and the pooled symptoms, duration of HIV/AIDS, poor self-efficacy and prevalence of depression, age was demonstrated to be lack of social support. However, we were unable to ob- linked with a higher risk of depression in studies with tain adequate information about these variables. For Zung SDS scores ≥50 or CES-D-20 scores ≥16 as the cri- example, less than 1/3 of the studies reported the teria for screening positive, which might support the posi- average or median counts of CD4 cells among HIV in- tive association between age and depression among PLHA fected populations, and fewer than 10 studies provided to some extent. However, as there were few studies using employment-specific prevalence estimates of depres- those two screening instrument cut-offs as screening cri- sion. In addition, although an extensive document re- teria, the results must be interpreted with caution. Further trieve was performed in multiple databases, the studies are needed to clarify the associations between gen- existence of non-indexed studies in those databases der/age and the risk of depression among PLHA, which might have led to some relevant studies being ignored. will help to identify individuals in high-risk. Moreover, although an attempt was made to minimize When interpreting the results of this study, note that the the possible bias in the process of document retrieving data synthesized in this meta-analysis were nearly entirely with specific searches in major English-Chinese data- extract from studies using self-report inventories of depres- bases (including master and doctoral theses), there sive symptoms as the survey instruments, which had a wide may still be some unidentified papers. Fortunately, as range of sensitivity and specificity for diagnosing major the results of Egger’s test results showed, there was no depressive disorder (Additional file 4). Instruments such as publication bias found in all results because we ob- the Psychological “Computerized Tomography” 4.0 Vision tained a certain percentage of data from unpublished (PCT V4.0) have high specificity and sensitivity for papers (fourteen theses [38, 56, 57, 66, 70, 71, 75, 82, diagnosing depression, whereas others instruments, 87, 89, 91, 94, 96, 99]). such as the SCL-90, have low specificity and should be regarded as screening tools. Furthermore, evidences Conclusions suggest that screening tools tend to over-estimate Our findings suggest that the estimates of depression prevalence relative to diagnostic tools, which may lead or depressive symptoms among PLHA in China are Wang et al. BMC Psychiatry (2018) 18:160 Page 11 of 14 considerable. Given that the progression of depression Competing interests The authors declare that they have no competing interests. are associated with a higher short-term suicide risk and a higher long-term risk of cardiovascular disease and cancer [134, 135], the findings in this study highlight Publisher’sNote the need for screening and treatment for mental disor- Springer Nature remains neutral with regard to jurisdictional claims in ders to be integrated in the treatment package offered published maps and institutional affiliations. to PLHA, which will ultimately lead to better health Author details outcomes for PLHA [136]. 1 Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China. Department of Mathematics, Mzuzu University, Mzuzu 2, Malawi. Additional files Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China. Department of Medical Psychology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Additional file 1: “Search strategy used in the current systematic review Province, China. and meta-analysis”. (DOC 66 kb) Additional file 2: “Modified Newcastle-Ottawa risk of bias scoring Received: 23 January 2018 Accepted: 11 May 2018 guide”. (DOC 27 kb) Additional file 3: “Selected characteristics of the 74 studies on the prevalence of depression or depressive symptoms among people living with HIV/AIDS in China”. (DOC 146 kb) References 1. World Health Organization. 10 facts on HIV/AIDS. 2017. http://www.who.int/ Additional file 4: “Modified Newcastle-Ottawa risk of bias score for the 74 features/factfiles/hiv/en/. Accessed 16 Sept 2017 studies included in this systematic review and meta-analysis”.(DOC 190 kb) 2. Chinese Center for Disease Control and Prevention. Update on the AIDS/ Additional file 5: “Sensitivities and specificities of commonly used STD epidemic in China and main response in control and prevention in instruments for diagnosing depression”. (DOC 43 kb) December, 2014. Chinese Journal of AIDS & STD. 2015;21:87. Additional file 6: “Sensitivity analysis of the prevalence of depression or 3. Chinese Center for Disease Control and Prevention. Update on the AIDS/ depressive symptoms among people living with HIV/AIDS in China”. STD epidemic in China in the second quarter of 2017. Chinese Journal of (PDF 157 kb) AIDS & STD. 2017;23:677. 4. Chinese Center for Disease Control and Prevention. Update on the AIDS/ Additional file 7: “Within-instrument heterogeneity analyses of studies STD epidemic in China and main response in control and prevention in reporting on the prevalence of depression or depressive symptoms December, 2015. 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We thank all our colleagues working in Department of Epidemiology and Psychiatric correlates of HAART utilization and viral load among HIV-positive Health Statistics, Xiangya School of public health of Central South University, impoverished persons. AIDS. 2011;25:1113–8. Dr. Li working in Department of Oncology, Xiangya Hospital of Central South 12. Sumari-de Boer IM, Sprangers MA, Prins JM, Nieuwkerk PT. HIV stigma and University and Dr. Guo working in Department of Medical Psychology, the depressive symptoms are related to adherence and virological response to Second Xiangya Hospital of Central South University. antiretroviral treatment among immigrant and indigenous HIV infected patients. AIDS Behav. 2012;16:1681–9. Availability of data and materials 13. Sabin CA, Ryom L, De Wit S, Mocroft A, Phillips AN, Worm SW, et al. 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BMC Psychiatry – Springer Journals

Published: May 31, 2018

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