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Nursing and Health Sciences (2015), 17, 250–256
Research Article
Mediation analysis of health-related quality of life among people living with HIV infection in China Xianhong Li, PhD, RN,1 Ling Li, MSN, RN,2 Honghong Wang, PhD, RN,1* Kristopher P. Fennie. PhD, MPH,3 Jia Chen, MSN, RN1 and Ann Bartley Williams, EdD, RNC, FAAN4 1
Xiangya School of Nursing, 2The Second Xiangya Hospital, Central South University, Changsha, China, 3Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida and 4School of Nursing, UCLA, Los Angeles, California, USA
Abstract
The effects of stigma, social support, and depressive symptoms on health-related quality of life are well documented in the literature, but how these psychological factors interact with each other, and the combined effects when taken together on the health-related quality of life for people living with HIV, remain unclear. This cross-sectional study investigated 114 people living with HIV who were taking antiretroviral medication using the HIV/AIDS-related Stigma Scale (Chinese version), the Social Support Rating Scale, the Center for Epidemiological Studies Depression Scale, and the Medical Outcomes Study–HIV health survey. Multiple linear regression analyses were used to examine the mediation effect of the psychosocial factors on healthrelated quality of life. Results showed that stigma and social support did not have direct effects, but indirect effects on health-related quality of life through a full mediation effect of depressive symptoms. The results indicate that interventions targeting depression might be the most effective approach to improving healthrelated quality of life among people living with HIV who are taking antiretroviral medication in China.
Key words
depression, HIV, quality of life, social support, stigma, China.
INTRODUCTION China has made remarkable progress in addressing its HIV epidemic. Over the past two decades, the official Chinese Government position has evolved from characterization of HIV as a disease of foreigners to recognition of the extent and complexity of the Chinese epidemic, leading ultimately to the development of a robust program of prevention, surveillance, and treatment. By the end of 2012, China’s national treatment program was delivering antiretroviral medications (ARV) to over 126,400 people in all provinces as a result of the “Four Frees and One Care” national policy (Ministry of Health of Peoples Republic of China, 2012). Globally, antiretroviral treatment has transformed HIV infection from a terminal disease to a long-term, manageable chronic illness. As a result, assessment of health-related quality of life (HRQOL), and understanding of the factors associated with HRQOL among people living with HIV (PLWH), is of increasing clinical and policy relevance (Beard et al., 2009). HRQOL among PLWH has been studied widely in high-income countries, and is associated with clinicallyimportant outcomes, including immunological improvement, treatment adherence, and virological changes (Liu et al., 2006; Jayaweera et al., 2009). However, data regarding
Correspondence address: Honghong Wang, Xiangya School of Nursing, Central South University, 172 Tong Zi Po Road, Changsha 410013, Hunan, China. Email: [email protected] Received 30 May 2014; revision received 20 August 2014; accepted 1 October 2014
© 2014 Wiley Publishing Asia Pty Ltd.
HRQOL among the majority of PLWH in low-income countries, including Chinese PLWH, are limited.
Literature review The concept of HRQOL as a major portion of overall quality of life, which includes multiple life domains, such as employment, housing, and health, emphasizes all the aspects of health influencing quality of life. These include physical and mental health perceptions at an individual level, and the practices, polices, or resources that influence an individual’s health perceptions and functional status at an environmental level (Zubritsky et al., 2013).Thus, HRQOL is a multifaceted variable reflecting an individual’s physical, mental, psychosocial, material, and spiritual well-being. For PLWH, HRQOL is associated with demographic, socioeconomic, and disease-related characteristics, including age, sex, educational background, place of residence (rural or urban), income, employment, drug abuse, and duration of HIV infection (He et al., 2012; Khumsaen et al., 2012). The importance of these factors suggests that HRQOL should be examined in a variety of countries and situations. Psychosocial factors, such as stigma, social support, and depressive symptoms, influence HRQOL. A meta-analysis of data from the USA and Africa revealed that perceived HIV stigma has a significant negative impact on HRQOL after controlling for disease-related characteristics (Holzemer et al., 2009). It is possible that stigma associated with HIV limits the willingness of PLWH to access medical treatment doi: 10.1111/nhs.12181
Depressive symptomology is a mediator
and care, isolates PLWH from family and community support, and creates cultural barriers that inhibit integration into social networks (Briongos Figuero et al., 2011). Dual stigma refers to HIV-related stigma combined with stigma toward homosexuality or drug abuse, and is of particular concern (Li et al., 2012). Social support is an important resource that allows people to buffer and manage perceived stress, and thus, potentially improve HRQOL. The components of social support fall into one of three domains: emotional, tangible, and informational support; the domains of emotional and informational support have more positive relationships with both mental and physical aspects of HRQOL than tangible support (Bajunirwe et al., 2009). Research has established that better social support from family members, friends, and healthcare providers predicts higher HRQOL (Bajunirwe et al., 2009; Bekele et al., 2013). Depressive symptoms are very common among PLWH around the world, with the prevalence ranging from 30% to 79% (Bing et al., 2001; Jin et al., 2006; Kagee & Martin, 2010; Dal-Bó et al., 2013). The negative impact of depressive symptoms on HRQOL among PLWH has been well documented. Symptoms, such as loss of interest, feelings of worthlessness and hopelessness, and recurrent thoughts of suicide, disrupt the daily life and self-management activities of PLWH (Tate et al., 2003; Jia et al., 2005; Charles et al., 2012). As discussed earlier, although the effects of stigma, social support, and depressive symptoms on HRQOL are well established, how these psychological factors interact with each other, and the combined effects when taken together on HRQOL for PLWH, remain unclear. Only a few studies have tried to explore the mediating relationships among these variables. A cross-sectional study of 120 PLWH in Beijing concluded that while stigma did not have a direct effect, it did have an indirect effect on HRQOL through the mediation of social support (Rao et al., 2012). Another study of over 600 Canadian PLWH revealed that social support could directly improve HRQOL, and also indirectly improve HRQOL by lowering depressive symptoms (Bekele et al., 2013).
Aim and hypothesis The goal of this analysis was to explore the direct and indirect effects of the psychosocial factors of stigma, social support, and depressive symptoms on HRQOL among PLWH in Hunan, China. The study hypotheses were: (i) stigma, social support, and depressive symptoms are each independently associated with HRQOL; (ii) stigma and social support each are also independently associated with depressive symptoms; and (iii) depressive symptoms have a direct effect on HRQOL, and mediate the relationships between stigma and HRQOL, and between social support and HRQOL.
METHODS This study was a cross-sectional analysis of baseline data collected for a study of a nursing intervention to improve medication adherence among PLWH in Hunan, China (Williams et al., 2013).
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Setting and sites The study was conducted in Hunan, a large Chinese province situated in the southeast of the country, where commercial sex work and injection drug use are main routes of HIV transmission (Wang et al., 2010; Williams et al., 2013). Data were collected at the two largest HIV clinical sites in Hunan province. At each site, PLWH receive similar comprehensive clinical care, including pre-ARV (compound sulfamethoxazole; multivitamins), ARV, medication adherence evaluation, CD4 tests, and HIV-resistance tests, when indicated.
Participants Participants were HIV-positive individuals, 18 years of age or older, who were taking pre-ARV or ARV at one of the two clinical sites, and self-reporting adherence less than 90% to prescribed doses of pre-ARV or ARV medications. Potential participants were informed about the study through flyers in the clinic or were referred by physicians. Participants with psychotic illnesses or who were cognitively impaired were excluded.
Data collection Data were collected during face-to-face structured interviews at the time of a regularly-scheduled clinical visit of the participants from July 2010 to August 2011. Graduate students, who were trained as research personnel and did not provide health services to the participants, conducted study interviews in a separate room of the clinic without the presence of the healthcare providers. All participation was voluntary and anonymous, and the information provided was kept confidential. The information provided was self-reported, with the exception of laboratory data (CD4 and HIV–RNA), which were taken from the medical records.
Ethical considerations The study protocol was reviewed by the Institutional Review Boards of Central South University (Changsha, China), the University of California (Los Angeles, CA, USA) and Yale University (New Haven, CT, USA). The two clinical sites do not have independent research review committees. Clinical staff were made aware of the study and were supportive. All participants were free to choose whether to participate, and provided written informed consent. Only the researchers carried out recruitment, enrollment, and data collection. Researchers were not included in the clinical care of the participants.
Measurements A structured questionnaire was used to record information regarding age, sex, marital status, education, place of residence, and employment. HIV-specific sociodemographic information gathered included presumed route of HIV acquisition, past or current injection drug use, length of time being diagnosed with HIV, and disclosing status. © 2014 Wiley Publishing Asia Pty Ltd.
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Stigma The HIV-related stigma and discrimination scale was developed in China and comprises 34 items that fall into five domains: disclosure concerns, public rejection, family stigma, internalized stigma, and healthcare providers’ discrimination. The instrument uses a five point Likert scoring method, with higher total scores indicating a higher level of perceived stigma. It has been tested among PLWH in Hunan province, and has demonstrated acceptable reliability and validity. Cronbach’s alpha of the scale was 0.90, and content validity was 0.88 (Li et al., 2010b).
Social support The Social Support Rating Scale is a Chinese instrument comprising 10 items with three subscales: objective social support, subjective social support, and support availability. Two month test–retest reliability is 0.92 (Xiao, 1999).
Depressive symptoms The Chinese version of the Centers for Epidemiological Studies Depression (CES-D) scale was used to evaluate depressive symptoms. It has 20 items, with higher scores indicating increased severity of depressive symptoms. The reliability of the scale has been established in the Chinese population (Zhang, 2002).
HRQOL The Chinese simplified version of the Medical Outcomes Study–HIV (MOS-HIV) health survey was used to measure HRQOL. The survey consists of 35 questions, which assess 10 dimensions of HRQOL. A standard-score method was used, with higher score indicating higher HRQOL. Reliability of the scale is acceptable, with Cronbach’s alpha 0.81 for the total scale, and 0.66–0.86 for the eight multi-item scales (Yang et al., 2007).
Analysis The data were examined initially for incompleteness, skewness, and distribution. Frequencies of all independent (stigma, social support, and depressive symptoms) and dependent (HRQOL) variables and correlations among them were examined using bivariate analysis. For mediation analyses, stepwise regression analysis, as recommended by Baron and Kenny (1986), was used to explore the mediation relationship, based on our small sample size. Following the steps for mediation analysis recommended by Wen et al. (2004), a regression model (model C) was conducted to estimate the associations between independent variables (stigma and social support) and HRQOL, controlling for demographic and disease-related characteristics. Then, in order to examine whether there was a possibility of mediation by depressive symptoms, two regression models were conducted to explore the association between depressive symptoms and HRQOL (model B), and the association between © 2014 Wiley Publishing Asia Pty Ltd.
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the independent variables (stigma and social support) and depressive symptoms (criterion variable) (model A). Finally, depressive symptoms were added into model C to examine whether the standardized beta weight for stigma and social support would be reduced or become non-significant.
RESULTS Demographic and clinical information A total of 114 participants completed the questionnaire; Their mean age was 39 years (range: 22–72 years). The mean length of time being diagnosed with HIV was 28 months (range: 14–85 months,) and the mean CD4 count was 142 cells/mm3, with a median of 116 cells/mm3 and a range of 8–428 cells/mm3. All participants had a detectable viral load, and all were prescribed an antiretroviral therapy regimen that included three drugs to be taken twice per day. Full sociodemographic and clinical information is presented in Table 1.
Correlation analyses of the variables Stigma, social support, and HRQOL were normally distributed. CES-D also was normally distributed, but the mean was quite high. A total of 66% of participants (n = 75) scored 16 or higher on the CES-D scale. The means, standard deviation, and correlations for all variables are presented in Table 2.The four psychosocial variables were moderately correlated with Pearson r, ranging from 0.37 to 0.77 (all P < 0.001) (Table 2).
Mediation analyses All demographic and disease-related variables that demonstrated significance in bivariate analysis (education, transmission route, employment, marital status, drug abuse, CD4, and ARV experience) were entered into the multivariate linear regression models as covariates. In a model unadjusted for depressive symptoms (model C), lower stigma (β = −0.33; 95% confidence interval [CI]: −0.49, −0.17; P < 0.001) and higher social support (β = 0.46; 95% CI: 0.08, 0.84; P < 0.05) were associated with better HRQOL (Table 3, Fig. 1), which supported the first hypothesis. Assessing the relationship between depressive symptoms and the independent variables stigma and social support (model A), greater depressive symptomatology was associated with higher levels of stigma (β = 0.24; 95% CI: 0.14, 0.35; P < 0.001) and lower levels of social support (β = −0.26; −0.51, −0.01; P < 0.05), which supported the second hypothesis. Additionally, depressive symptoms also were associated with lower HRQOL (β = −1.06; 95% CI: −1.28, −0.85; P < 0.001) (model B), by which the first hypothesis was supported. This suggests that a mediation relationship might exist. Adding the potential mediator of “depressive symptoms” into the original model (model C), stigma (β = −0.10; 95% CI: −0.25, 0.04; P = 0.46) and social support (β = −0.22; 95% CI: −0.10, 0.53; P = 0.24) were no longer significantly associated with HRQOL, while depressive symptoms were significantly
Depressive symptomology is a mediator
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Table 1. Participants’ sociodemographic and clinical information (n = 114) Item Age Sex Marital status
Education background
Residence Employment
Household income per year ($US)
Drug abuse Transmission routes
Length since diagnosis† Household know CD4 counts (cells/mm3)
Frequency/mean
%/standard deviation
39 81 28 59 8 11 8 4 13 50 36 11 26 58 26 30 35 23 29 16 6 5 35 44 14 31 6 19 89 82 75 38 1
10.2 71.1 24.6 51.8 7.0 9.6 7.0 3.5 11.4 43.9 31.6 9.6 22.8 50.9 22.8 26.3 30.7 20.2 25.4 14.0 5.3 4.4 30.7 38.6 12.3 27.2 5.3 16.7 78.1 71.9 65.8 33.3 0.9
Male Single Married or have a regular sexual partner Married, but separated Divorced Widowed No formal school Primary school Middle school High school University or vocational Rural area Unemployed Employed occasionally Employed regularly < 5000 5000–9999 1612–3225 3226–6450 6451–9677 ≥ 9678 Yes Heterosexual Homosexual Sharing needles Blood route Unclear ≤ 24 months Yes < 200 200–349 ≥ 350
†Four cases missing.
Table 2.
Means, standard deviations, and intercorrelations for stigma, social support, depressive symptoms, and quality of life
Variables (possible range)
Mean
Standard deviation
(1)
(2)
(3)
(4)
(1) Stigma (34–170) (2) Social support (12–68) (3) Depressive symptoms (0–60) (4) Quality of life (0–100)
105.03 31.96 21.90 62.94
20.10 8.44 12.45 19.28
1 −0.37** 0.58** −0.53**
1 −0.44** −0.44**
1 −0.77**
1
Pearson’s correlations (two tailed).
associated with HRQOL (β = −0.93; 95% CI: −1.12, −0.69; P < 0.001), indicating a full mediation relationship of depressive symptoms (Fig. 1). Thus, the third hypothesis was supported.
DISCUSSION In this study, the direct and indirect effects of the psychosocial factors of stigma, social support, and depressive symptoms on HRQOL among PLWH in China were explored.
Consistent with other studies (Bajunirwe et al., 2009; Holzemer et al., 2009; Bekele et al., 2013), our results confirmed that high levels of HIV stigma and low levels of social support were directly associated with poor HRQOL without considering depressive symptoms. However, in addition, and as hypothesized, stigma and social support in fact directly influenced depressive symptoms, and then affected HRQOL, which demonstrated that depressive symptoms was a mediator in these relationships. There are three potential explanations for this important finding. © 2014 Wiley Publishing Asia Pty Ltd.
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Table 3.
Mediation analysis by multivariable linear regressions (n = 114)
Dependent variable
Independent variable
Unstandardized β
Standard error
F
Adjusted R2
Step 1 Model C
QOL
Stigma Social support
−0.33** 0.46*
0.08 0.19
6.70**
0.43
Step 2 Model A
Depressive symptoms
Stigma Social support Depressive symptoms
0.24** −0.26* −1.06**
0.05 0.13 0.11
6.50**
0.42
14.41**
0.62
Stigma Social support Depressive symptoms
−0.10 0.22 −0.93**
0.07 0.16 0.12
13.26**
0.63
Model B Step 3 Model C’
QOL QOL
*P < 0.05, **P < 0.001. QOL, quality of life.
Mediator Depressive symptoms Stigma: 0.24** (95% Cl: 0.14~0.35) Social support: −0.26* (95% Cl: −0.51~−0.01)
−1.06** (95% Cl: −1.28~−0.85) Without mediator
Stigma: −0.33**(95% Cl: −0.49~−0.17) Social support: 0.46*(95% Cl: 0.08~0.84) Quality of life
Stigma Social support With mediator Stigma: −0.10 (95% Cl: −0.25~0.04) Social support: 0.22 (95% Cl: −0.10~0.53)
First, it is possible that stigma, especially internalized stigma, leads to low self-esteem and negative self-image (Charles et al., 2012; Li et al., 2012), and thereby contributes to depressive symptoms. In addition, a low level of social support from family, friends, and social associations might further limit opportunities for communication and encouragement that would counteract the depressive symptoms (Rao et al., 2012). Patients with more depressive symptoms might report a lower HRQOL, as we discussed in the Introduction section of this paper. Second, the prevalence of depressive symptomology in this population was very high. The CES-D scale measures depressive symptoms, rather than a clinical diagnosis of depression. The proportion of participants reporting a high level of depressive symptomology in our study (66%) is consistent with the results of another Chinese study, which concluded that 79% of PLWH were depressed, as measured by the Beck Depression Inventory (Jin et al., 2006). The prevalence of depressive symptomology among PLWH was markedly higher than in a general population in China (6.9%) (Ma et al., 2007). Additionally, early symptoms of depression among PLWH are largely untreated. One of the reasons for lack of treat© 2014 Wiley Publishing Asia Pty Ltd.
Figure 1. Mediation analyses among social support, stigma, depressive symptoms, and quality of life. Unstandardized beta weights of each variable in the series of regression analyses are shown: *P < 0.05, *P < 0.01. CI, confidence interval.
ment is that there are no psychiatrists, psychologists, or psychiatric nurses assigned to Chinese HIV clinics (Li et al., 2011). Further, depression, like all psychiatric disorders, is highly stigmatized in China, and treatment is available only at limited and often isolated locations (Xu et al., 2012). As a result, patients rarely accept referrals for mental health treatment, even when they are made. Last but not least, the concepts of depression and HRQOL that we measured partially overlap. According to Paykel (2008, p. 279, 286), “the term ‘depression’ came into use in the 19th century, originally as ‘mental depression’, to describe lowering of spirits”. More recently, the core symptoms of depression are widely recognized as including at least depressed mood, decreased energy, or fatigability. These also are components of the MOS-HIV scale to evaluate HRQOL, namely the “mental health summary”, which describes respondents’ mental well-being. The implication of this mediation analysis is that interventions should focus not only on reducing stigma and improving social support, but also more importantly on ameliorating depressive symptoms. In China, the issues of HIV stigma and social support have been addressed by the government, healthcare providers, and researchers during the past two
Depressive symptomology is a mediator
decades, through programs such as the “Four Frees and One Care” policy (Ministry of Health of Peoples Republic of China, 2012). Some researchers have addressed the stigma issue by conceptualizing it within the Chinese cultural background, and working toward reducing it by involving family members (Wang et al., 2010; Li et al., 2012). In addition, interventions to reduce the stigmatizing attitudes of healthcare providers and improve their support for PLWH began years ago (Wu et al., 2008; Li et al., 2010a).). However, interventions targeting depressive symptoms among PLWH in China are still rare. There are several limitations to this study. First, structural equation modeling (or path analysis), a more powerful statistical technique, could not be conducted due to the relatively small sample size. However, as recommended by Baron and Kenny (1986), the mediation analysis was done by regression analysis using a relatively small sample size. This sample size was consistent with similar studies in the literature (Lehmann-Willenbrock et al., 2012; Rao et al., 2012). Moreover, we detected significant relationships among variables; therefore, we had sufficient power. Second, because the sample was drawn from patients in clinical care for whom ARV therapy had been recommended, the results might not be generalizable to PLWH with less advanced disease or to those not in care.Third, these data are cross-sectional; therefore, inferences about causality must be interpreted with caution.
Conclusions This study confirmed that stigma, social support, and depressive symptoms were the main factors associated with HRQOL among PLWH in China. It also pointed out that depressive symptoms are an important pathway connecting stigma, social support, and HRQOL. The results of our study, especially when taken in the context of limited mental health services, suggest that China is facing a significant problem that must be addressed urgently if the full benefits of advances in HIV care are to be realized for its citizens. Future studies and clinical practices seeking to improve HRQOL among PLWH in China should certainly include alleviating depressive symptoms as a primary goal.
ACKNOWLEDGMENTS We gratefully acknowledge the health providers and participants at the Sixth Hospital of Changsha and the Third Hospital of Hengyang in Hunan province. We also thank Dr Lynn Brecht, School of Nursing, UCLA, for consultation regarding the mediation analysis. This research was supported by a grant from the U. S. National Institutes of Health (R34 MH 083564-01A2).
CONTRIBUTIONS Study Design: AW, HW. Data Collection and Analysis: XL, LL, KF, JC. Manuscript Writing: XL, AW, HW.
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Nursing and Health Sciences (2015), 17, 250–256
Research Article
Mediation analysis of health-related quality of life among people living with HIV infection in China Xianhong Li, PhD, RN,1 Ling Li, MSN, RN,2 Honghong Wang, PhD, RN,1* Kristopher P. Fennie. PhD, MPH,3 Jia Chen, MSN, RN1 and Ann Bartley Williams, EdD, RNC, FAAN4 1
Xiangya School of Nursing, 2The Second Xiangya Hospital, Central South University, Changsha, China, 3Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida and 4School of Nursing, UCLA, Los Angeles, California, USA
Abstract
The effects of stigma, social support, and depressive symptoms on health-related quality of life are well documented in the literature, but how these psychological factors interact with each other, and the combined effects when taken together on the health-related quality of life for people living with HIV, remain unclear. This cross-sectional study investigated 114 people living with HIV who were taking antiretroviral medication using the HIV/AIDS-related Stigma Scale (Chinese version), the Social Support Rating Scale, the Center for Epidemiological Studies Depression Scale, and the Medical Outcomes Study–HIV health survey. Multiple linear regression analyses were used to examine the mediation effect of the psychosocial factors on healthrelated quality of life. Results showed that stigma and social support did not have direct effects, but indirect effects on health-related quality of life through a full mediation effect of depressive symptoms. The results indicate that interventions targeting depression might be the most effective approach to improving healthrelated quality of life among people living with HIV who are taking antiretroviral medication in China.
Key words
depression, HIV, quality of life, social support, stigma, China.
INTRODUCTION China has made remarkable progress in addressing its HIV epidemic. Over the past two decades, the official Chinese Government position has evolved from characterization of HIV as a disease of foreigners to recognition of the extent and complexity of the Chinese epidemic, leading ultimately to the development of a robust program of prevention, surveillance, and treatment. By the end of 2012, China’s national treatment program was delivering antiretroviral medications (ARV) to over 126,400 people in all provinces as a result of the “Four Frees and One Care” national policy (Ministry of Health of Peoples Republic of China, 2012). Globally, antiretroviral treatment has transformed HIV infection from a terminal disease to a long-term, manageable chronic illness. As a result, assessment of health-related quality of life (HRQOL), and understanding of the factors associated with HRQOL among people living with HIV (PLWH), is of increasing clinical and policy relevance (Beard et al., 2009). HRQOL among PLWH has been studied widely in high-income countries, and is associated with clinicallyimportant outcomes, including immunological improvement, treatment adherence, and virological changes (Liu et al., 2006; Jayaweera et al., 2009). However, data regarding
Correspondence address: Honghong Wang, Xiangya School of Nursing, Central South University, 172 Tong Zi Po Road, Changsha 410013, Hunan, China. Email: [email protected] Received 30 May 2014; revision received 20 August 2014; accepted 1 October 2014
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HRQOL among the majority of PLWH in low-income countries, including Chinese PLWH, are limited.
Literature review The concept of HRQOL as a major portion of overall quality of life, which includes multiple life domains, such as employment, housing, and health, emphasizes all the aspects of health influencing quality of life. These include physical and mental health perceptions at an individual level, and the practices, polices, or resources that influence an individual’s health perceptions and functional status at an environmental level (Zubritsky et al., 2013).Thus, HRQOL is a multifaceted variable reflecting an individual’s physical, mental, psychosocial, material, and spiritual well-being. For PLWH, HRQOL is associated with demographic, socioeconomic, and disease-related characteristics, including age, sex, educational background, place of residence (rural or urban), income, employment, drug abuse, and duration of HIV infection (He et al., 2012; Khumsaen et al., 2012). The importance of these factors suggests that HRQOL should be examined in a variety of countries and situations. Psychosocial factors, such as stigma, social support, and depressive symptoms, influence HRQOL. A meta-analysis of data from the USA and Africa revealed that perceived HIV stigma has a significant negative impact on HRQOL after controlling for disease-related characteristics (Holzemer et al., 2009). It is possible that stigma associated with HIV limits the willingness of PLWH to access medical treatment doi: 10.1111/nhs.12181
Depressive symptomology is a mediator
and care, isolates PLWH from family and community support, and creates cultural barriers that inhibit integration into social networks (Briongos Figuero et al., 2011). Dual stigma refers to HIV-related stigma combined with stigma toward homosexuality or drug abuse, and is of particular concern (Li et al., 2012). Social support is an important resource that allows people to buffer and manage perceived stress, and thus, potentially improve HRQOL. The components of social support fall into one of three domains: emotional, tangible, and informational support; the domains of emotional and informational support have more positive relationships with both mental and physical aspects of HRQOL than tangible support (Bajunirwe et al., 2009). Research has established that better social support from family members, friends, and healthcare providers predicts higher HRQOL (Bajunirwe et al., 2009; Bekele et al., 2013). Depressive symptoms are very common among PLWH around the world, with the prevalence ranging from 30% to 79% (Bing et al., 2001; Jin et al., 2006; Kagee & Martin, 2010; Dal-Bó et al., 2013). The negative impact of depressive symptoms on HRQOL among PLWH has been well documented. Symptoms, such as loss of interest, feelings of worthlessness and hopelessness, and recurrent thoughts of suicide, disrupt the daily life and self-management activities of PLWH (Tate et al., 2003; Jia et al., 2005; Charles et al., 2012). As discussed earlier, although the effects of stigma, social support, and depressive symptoms on HRQOL are well established, how these psychological factors interact with each other, and the combined effects when taken together on HRQOL for PLWH, remain unclear. Only a few studies have tried to explore the mediating relationships among these variables. A cross-sectional study of 120 PLWH in Beijing concluded that while stigma did not have a direct effect, it did have an indirect effect on HRQOL through the mediation of social support (Rao et al., 2012). Another study of over 600 Canadian PLWH revealed that social support could directly improve HRQOL, and also indirectly improve HRQOL by lowering depressive symptoms (Bekele et al., 2013).
Aim and hypothesis The goal of this analysis was to explore the direct and indirect effects of the psychosocial factors of stigma, social support, and depressive symptoms on HRQOL among PLWH in Hunan, China. The study hypotheses were: (i) stigma, social support, and depressive symptoms are each independently associated with HRQOL; (ii) stigma and social support each are also independently associated with depressive symptoms; and (iii) depressive symptoms have a direct effect on HRQOL, and mediate the relationships between stigma and HRQOL, and between social support and HRQOL.
METHODS This study was a cross-sectional analysis of baseline data collected for a study of a nursing intervention to improve medication adherence among PLWH in Hunan, China (Williams et al., 2013).
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Setting and sites The study was conducted in Hunan, a large Chinese province situated in the southeast of the country, where commercial sex work and injection drug use are main routes of HIV transmission (Wang et al., 2010; Williams et al., 2013). Data were collected at the two largest HIV clinical sites in Hunan province. At each site, PLWH receive similar comprehensive clinical care, including pre-ARV (compound sulfamethoxazole; multivitamins), ARV, medication adherence evaluation, CD4 tests, and HIV-resistance tests, when indicated.
Participants Participants were HIV-positive individuals, 18 years of age or older, who were taking pre-ARV or ARV at one of the two clinical sites, and self-reporting adherence less than 90% to prescribed doses of pre-ARV or ARV medications. Potential participants were informed about the study through flyers in the clinic or were referred by physicians. Participants with psychotic illnesses or who were cognitively impaired were excluded.
Data collection Data were collected during face-to-face structured interviews at the time of a regularly-scheduled clinical visit of the participants from July 2010 to August 2011. Graduate students, who were trained as research personnel and did not provide health services to the participants, conducted study interviews in a separate room of the clinic without the presence of the healthcare providers. All participation was voluntary and anonymous, and the information provided was kept confidential. The information provided was self-reported, with the exception of laboratory data (CD4 and HIV–RNA), which were taken from the medical records.
Ethical considerations The study protocol was reviewed by the Institutional Review Boards of Central South University (Changsha, China), the University of California (Los Angeles, CA, USA) and Yale University (New Haven, CT, USA). The two clinical sites do not have independent research review committees. Clinical staff were made aware of the study and were supportive. All participants were free to choose whether to participate, and provided written informed consent. Only the researchers carried out recruitment, enrollment, and data collection. Researchers were not included in the clinical care of the participants.
Measurements A structured questionnaire was used to record information regarding age, sex, marital status, education, place of residence, and employment. HIV-specific sociodemographic information gathered included presumed route of HIV acquisition, past or current injection drug use, length of time being diagnosed with HIV, and disclosing status. © 2014 Wiley Publishing Asia Pty Ltd.
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Stigma The HIV-related stigma and discrimination scale was developed in China and comprises 34 items that fall into five domains: disclosure concerns, public rejection, family stigma, internalized stigma, and healthcare providers’ discrimination. The instrument uses a five point Likert scoring method, with higher total scores indicating a higher level of perceived stigma. It has been tested among PLWH in Hunan province, and has demonstrated acceptable reliability and validity. Cronbach’s alpha of the scale was 0.90, and content validity was 0.88 (Li et al., 2010b).
Social support The Social Support Rating Scale is a Chinese instrument comprising 10 items with three subscales: objective social support, subjective social support, and support availability. Two month test–retest reliability is 0.92 (Xiao, 1999).
Depressive symptoms The Chinese version of the Centers for Epidemiological Studies Depression (CES-D) scale was used to evaluate depressive symptoms. It has 20 items, with higher scores indicating increased severity of depressive symptoms. The reliability of the scale has been established in the Chinese population (Zhang, 2002).
HRQOL The Chinese simplified version of the Medical Outcomes Study–HIV (MOS-HIV) health survey was used to measure HRQOL. The survey consists of 35 questions, which assess 10 dimensions of HRQOL. A standard-score method was used, with higher score indicating higher HRQOL. Reliability of the scale is acceptable, with Cronbach’s alpha 0.81 for the total scale, and 0.66–0.86 for the eight multi-item scales (Yang et al., 2007).
Analysis The data were examined initially for incompleteness, skewness, and distribution. Frequencies of all independent (stigma, social support, and depressive symptoms) and dependent (HRQOL) variables and correlations among them were examined using bivariate analysis. For mediation analyses, stepwise regression analysis, as recommended by Baron and Kenny (1986), was used to explore the mediation relationship, based on our small sample size. Following the steps for mediation analysis recommended by Wen et al. (2004), a regression model (model C) was conducted to estimate the associations between independent variables (stigma and social support) and HRQOL, controlling for demographic and disease-related characteristics. Then, in order to examine whether there was a possibility of mediation by depressive symptoms, two regression models were conducted to explore the association between depressive symptoms and HRQOL (model B), and the association between © 2014 Wiley Publishing Asia Pty Ltd.
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the independent variables (stigma and social support) and depressive symptoms (criterion variable) (model A). Finally, depressive symptoms were added into model C to examine whether the standardized beta weight for stigma and social support would be reduced or become non-significant.
RESULTS Demographic and clinical information A total of 114 participants completed the questionnaire; Their mean age was 39 years (range: 22–72 years). The mean length of time being diagnosed with HIV was 28 months (range: 14–85 months,) and the mean CD4 count was 142 cells/mm3, with a median of 116 cells/mm3 and a range of 8–428 cells/mm3. All participants had a detectable viral load, and all were prescribed an antiretroviral therapy regimen that included three drugs to be taken twice per day. Full sociodemographic and clinical information is presented in Table 1.
Correlation analyses of the variables Stigma, social support, and HRQOL were normally distributed. CES-D also was normally distributed, but the mean was quite high. A total of 66% of participants (n = 75) scored 16 or higher on the CES-D scale. The means, standard deviation, and correlations for all variables are presented in Table 2.The four psychosocial variables were moderately correlated with Pearson r, ranging from 0.37 to 0.77 (all P < 0.001) (Table 2).
Mediation analyses All demographic and disease-related variables that demonstrated significance in bivariate analysis (education, transmission route, employment, marital status, drug abuse, CD4, and ARV experience) were entered into the multivariate linear regression models as covariates. In a model unadjusted for depressive symptoms (model C), lower stigma (β = −0.33; 95% confidence interval [CI]: −0.49, −0.17; P < 0.001) and higher social support (β = 0.46; 95% CI: 0.08, 0.84; P < 0.05) were associated with better HRQOL (Table 3, Fig. 1), which supported the first hypothesis. Assessing the relationship between depressive symptoms and the independent variables stigma and social support (model A), greater depressive symptomatology was associated with higher levels of stigma (β = 0.24; 95% CI: 0.14, 0.35; P < 0.001) and lower levels of social support (β = −0.26; −0.51, −0.01; P < 0.05), which supported the second hypothesis. Additionally, depressive symptoms also were associated with lower HRQOL (β = −1.06; 95% CI: −1.28, −0.85; P < 0.001) (model B), by which the first hypothesis was supported. This suggests that a mediation relationship might exist. Adding the potential mediator of “depressive symptoms” into the original model (model C), stigma (β = −0.10; 95% CI: −0.25, 0.04; P = 0.46) and social support (β = −0.22; 95% CI: −0.10, 0.53; P = 0.24) were no longer significantly associated with HRQOL, while depressive symptoms were significantly
Depressive symptomology is a mediator
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Table 1. Participants’ sociodemographic and clinical information (n = 114) Item Age Sex Marital status
Education background
Residence Employment
Household income per year ($US)
Drug abuse Transmission routes
Length since diagnosis† Household know CD4 counts (cells/mm3)
Frequency/mean
%/standard deviation
39 81 28 59 8 11 8 4 13 50 36 11 26 58 26 30 35 23 29 16 6 5 35 44 14 31 6 19 89 82 75 38 1
10.2 71.1 24.6 51.8 7.0 9.6 7.0 3.5 11.4 43.9 31.6 9.6 22.8 50.9 22.8 26.3 30.7 20.2 25.4 14.0 5.3 4.4 30.7 38.6 12.3 27.2 5.3 16.7 78.1 71.9 65.8 33.3 0.9
Male Single Married or have a regular sexual partner Married, but separated Divorced Widowed No formal school Primary school Middle school High school University or vocational Rural area Unemployed Employed occasionally Employed regularly < 5000 5000–9999 1612–3225 3226–6450 6451–9677 ≥ 9678 Yes Heterosexual Homosexual Sharing needles Blood route Unclear ≤ 24 months Yes < 200 200–349 ≥ 350
†Four cases missing.
Table 2.
Means, standard deviations, and intercorrelations for stigma, social support, depressive symptoms, and quality of life
Variables (possible range)
Mean
Standard deviation
(1)
(2)
(3)
(4)
(1) Stigma (34–170) (2) Social support (12–68) (3) Depressive symptoms (0–60) (4) Quality of life (0–100)
105.03 31.96 21.90 62.94
20.10 8.44 12.45 19.28
1 −0.37** 0.58** −0.53**
1 −0.44** −0.44**
1 −0.77**
1
Pearson’s correlations (two tailed).
associated with HRQOL (β = −0.93; 95% CI: −1.12, −0.69; P < 0.001), indicating a full mediation relationship of depressive symptoms (Fig. 1). Thus, the third hypothesis was supported.
DISCUSSION In this study, the direct and indirect effects of the psychosocial factors of stigma, social support, and depressive symptoms on HRQOL among PLWH in China were explored.
Consistent with other studies (Bajunirwe et al., 2009; Holzemer et al., 2009; Bekele et al., 2013), our results confirmed that high levels of HIV stigma and low levels of social support were directly associated with poor HRQOL without considering depressive symptoms. However, in addition, and as hypothesized, stigma and social support in fact directly influenced depressive symptoms, and then affected HRQOL, which demonstrated that depressive symptoms was a mediator in these relationships. There are three potential explanations for this important finding. © 2014 Wiley Publishing Asia Pty Ltd.
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Table 3.
Mediation analysis by multivariable linear regressions (n = 114)
Dependent variable
Independent variable
Unstandardized β
Standard error
F
Adjusted R2
Step 1 Model C
QOL
Stigma Social support
−0.33** 0.46*
0.08 0.19
6.70**
0.43
Step 2 Model A
Depressive symptoms
Stigma Social support Depressive symptoms
0.24** −0.26* −1.06**
0.05 0.13 0.11
6.50**
0.42
14.41**
0.62
Stigma Social support Depressive symptoms
−0.10 0.22 −0.93**
0.07 0.16 0.12
13.26**
0.63
Model B Step 3 Model C’
QOL QOL
*P < 0.05, **P < 0.001. QOL, quality of life.
Mediator Depressive symptoms Stigma: 0.24** (95% Cl: 0.14~0.35) Social support: −0.26* (95% Cl: −0.51~−0.01)
−1.06** (95% Cl: −1.28~−0.85) Without mediator
Stigma: −0.33**(95% Cl: −0.49~−0.17) Social support: 0.46*(95% Cl: 0.08~0.84) Quality of life
Stigma Social support With mediator Stigma: −0.10 (95% Cl: −0.25~0.04) Social support: 0.22 (95% Cl: −0.10~0.53)
First, it is possible that stigma, especially internalized stigma, leads to low self-esteem and negative self-image (Charles et al., 2012; Li et al., 2012), and thereby contributes to depressive symptoms. In addition, a low level of social support from family, friends, and social associations might further limit opportunities for communication and encouragement that would counteract the depressive symptoms (Rao et al., 2012). Patients with more depressive symptoms might report a lower HRQOL, as we discussed in the Introduction section of this paper. Second, the prevalence of depressive symptomology in this population was very high. The CES-D scale measures depressive symptoms, rather than a clinical diagnosis of depression. The proportion of participants reporting a high level of depressive symptomology in our study (66%) is consistent with the results of another Chinese study, which concluded that 79% of PLWH were depressed, as measured by the Beck Depression Inventory (Jin et al., 2006). The prevalence of depressive symptomology among PLWH was markedly higher than in a general population in China (6.9%) (Ma et al., 2007). Additionally, early symptoms of depression among PLWH are largely untreated. One of the reasons for lack of treat© 2014 Wiley Publishing Asia Pty Ltd.
Figure 1. Mediation analyses among social support, stigma, depressive symptoms, and quality of life. Unstandardized beta weights of each variable in the series of regression analyses are shown: *P < 0.05, *P < 0.01. CI, confidence interval.
ment is that there are no psychiatrists, psychologists, or psychiatric nurses assigned to Chinese HIV clinics (Li et al., 2011). Further, depression, like all psychiatric disorders, is highly stigmatized in China, and treatment is available only at limited and often isolated locations (Xu et al., 2012). As a result, patients rarely accept referrals for mental health treatment, even when they are made. Last but not least, the concepts of depression and HRQOL that we measured partially overlap. According to Paykel (2008, p. 279, 286), “the term ‘depression’ came into use in the 19th century, originally as ‘mental depression’, to describe lowering of spirits”. More recently, the core symptoms of depression are widely recognized as including at least depressed mood, decreased energy, or fatigability. These also are components of the MOS-HIV scale to evaluate HRQOL, namely the “mental health summary”, which describes respondents’ mental well-being. The implication of this mediation analysis is that interventions should focus not only on reducing stigma and improving social support, but also more importantly on ameliorating depressive symptoms. In China, the issues of HIV stigma and social support have been addressed by the government, healthcare providers, and researchers during the past two
Depressive symptomology is a mediator
decades, through programs such as the “Four Frees and One Care” policy (Ministry of Health of Peoples Republic of China, 2012). Some researchers have addressed the stigma issue by conceptualizing it within the Chinese cultural background, and working toward reducing it by involving family members (Wang et al., 2010; Li et al., 2012). In addition, interventions to reduce the stigmatizing attitudes of healthcare providers and improve their support for PLWH began years ago (Wu et al., 2008; Li et al., 2010a).). However, interventions targeting depressive symptoms among PLWH in China are still rare. There are several limitations to this study. First, structural equation modeling (or path analysis), a more powerful statistical technique, could not be conducted due to the relatively small sample size. However, as recommended by Baron and Kenny (1986), the mediation analysis was done by regression analysis using a relatively small sample size. This sample size was consistent with similar studies in the literature (Lehmann-Willenbrock et al., 2012; Rao et al., 2012). Moreover, we detected significant relationships among variables; therefore, we had sufficient power. Second, because the sample was drawn from patients in clinical care for whom ARV therapy had been recommended, the results might not be generalizable to PLWH with less advanced disease or to those not in care.Third, these data are cross-sectional; therefore, inferences about causality must be interpreted with caution.
Conclusions This study confirmed that stigma, social support, and depressive symptoms were the main factors associated with HRQOL among PLWH in China. It also pointed out that depressive symptoms are an important pathway connecting stigma, social support, and HRQOL. The results of our study, especially when taken in the context of limited mental health services, suggest that China is facing a significant problem that must be addressed urgently if the full benefits of advances in HIV care are to be realized for its citizens. Future studies and clinical practices seeking to improve HRQOL among PLWH in China should certainly include alleviating depressive symptoms as a primary goal.
ACKNOWLEDGMENTS We gratefully acknowledge the health providers and participants at the Sixth Hospital of Changsha and the Third Hospital of Hengyang in Hunan province. We also thank Dr Lynn Brecht, School of Nursing, UCLA, for consultation regarding the mediation analysis. This research was supported by a grant from the U. S. National Institutes of Health (R34 MH 083564-01A2).
CONTRIBUTIONS Study Design: AW, HW. Data Collection and Analysis: XL, LL, KF, JC. Manuscript Writing: XL, AW, HW.
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