Structural Equation Modeling of Depression, Stigma, and Social Support among People Living with HIV on Second-Line ART in Northeast Ethiopia: A Cross-Sectional Study

Structural Equation Modeling of Depression, Stigma, and Social Support among People Living with HIV on Second-Line ART in Northeast Ethiopia: A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Structural Equation Modeling of Depression, Stigma, and Social Support among People Living with HIV on Second-Line ART in Northeast Ethiopia: A Cross-Sectional Study Keleb Takele Tiruneh, Ziyin Worku This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8907378/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Stigma forces individuals to hide their HIV status, discourages medical visits, hinders medication adherence, and restricts access to social support. HIV stigma refers to the process in which people living with HIV are socially discredited and devalued due to their HIV status. Hence, the aim of this study was to determine internalized stigma and associated factors among PLHIV on second-line ART in northeast Ethiopia. Method A facility-based cross-sectional study was conducted from January 13 to April 13, 2025, involving 825 randomly selected PLHIV on second-line ART. Data were gathered through document review and face-to-face interviews and analyzed with STATA version 17. Depression, social support and internalized stigma were assessed using the PHQ-9, Oslo-3 scales and HIV stigma scale, respectively. Structural equation modeling was applied, with statistical significance set at P < 0.05 and effect sizes reported with 95% confidence intervals. Result In structural equation model, internalized stigma was significantly associated with depression [ \(\:\widehat{\beta\:}\) = 0.19, (95% CI: 0.11–0.26)] and perceived stigma [ \(\:\widehat{\beta\:}\) = 0.92, (95% CI: 0.806–1.042)], indicating that higher level of depression and perceived stigma were related to higher level of internalized stigma. Whereas, social support was inversely associated with internalized stigma [ \(\:\widehat{\beta\:}\) = -0.80, (95% CI: -0.862 to -0.732)], suggesting that greater social support was linked to lower internalized stigma. Conclusion This finding suggests that perceived stigma and depression fully mediate the relationship between social support and internalized stigma among PLHIV on second-line ART. Moreover, perceived stigma and depression functioned as parallel mediators in the relationship between social support and internalized stigma while also having a direct positive effect on internalized stigma. Social support, perceived stigmas and depression were significance predictors of internalized stigma. Health sciences/Diseases Health sciences/Health care Biological sciences/Psychology Social science/Psychology Structural Equation Modeling Internalized Stigma PLHIV Second-Line ART Figures Figure 1 Figure 2 Figure 3 Introduction HIV/AIDS remains a major global public health challenge, with sub-Saharan Africa (SSA) bearing the highest burden, accounting for over two-thirds of all reported cases[1]. The global availability of HIV treatment medications is a significant advancement in achieving USAID’s 90-90-90 targets [2, 3]. Due to the effectiveness of combination antiretroviral therapy (ART), people living with HIV (PLWH) can achieve life expectancies close to those of the general population[4]. Although ART has increased the life expectancy of people living with HIV (PLWH), they still face various health challenges, including opportunistic infections, syphilis, tuberculosis, and widespread HIV-related stigma [3, 5]. Furthermore, HIV/AIDS continues to be a major barrier to Ethiopia's overall development, contributing to a seven-year reduction in life expectancy and a significant decline in the workforce [6]. Stigma forces individuals to hide their HIV status, discourages medical visits, hinders medication adherence, and restricts access to social support [7, 8]. HIV stigma refers to the process in which people living with HIV (PLWH) are socially discredited and devalued due to their HIV status [4, 9, 10]. Furthermore, stigma was traditionally defined as “a significantly discrediting trait” and later broadened to mean “a powerful discrediting and tainting social label that fundamentally alters how individuals perceive themselves and how they are perceived by others” [3, 11, 12]. Additionally, individuals diagnosed with HIV/AIDS may face stigma because the modes of HIV transmission are often perceived as controllable, along with the associated HIV-related risk behaviors [3, 13]. Moreover, because HIV/AIDS is viewed as a degenerative and incurable disease, people may harbor fears such as fear of the disease, contagion, and death towards those living with HIV, which can result in widespread stigma [3, 8, 14]. On the other hand, people living with HIV (PLWH) who perceive themselves as responsible for their own actions are more likely to experience intense feelings of shame and guilt [4, 8, 15]. Perceived and internalized stigma (PIS) encompasses two significant forms of stigma that are common among people living with HIV (PLWH) and are closely linked to mental and behavioral health [3, 4, 8, 16–18]. Perceived HIV-related stigma is defined as the recognition of discriminatory and prejudicial attitudes directed towards individuals by members of society [17, 18]. Furthermore, individuals who internalize stigma tend to develop negative beliefs and self-images, often accompanied by low self-esteem, due to adopting the negative perceptions held by society [3, 7]. Individuals who perceive stigma from others in society are often vulnerable to feelings of self-hatred, particularly when they internalize society's negative views of themselves [7, 17]. As a result, the combined effects of perceived and internalized stigma can lead to various consequences, including non-disclosure of HIV status, social isolation, and depressive symptoms [4, 17, 19]. Although internalized stigma is influenced by depression, social support, and perceived stigma both directly and indirectly, there is no literature within the Ethiopian context that determines the direct and indirect effects of these covariates on internalized stigma among people living with HIV (PLHIV) on second-line ART. While some studies have attempted to measure internalized stigma, these publications have treated it as a predictor variable rather than determining it as a latent outcome variable, and they fail to account for measurement error in the latent construct. To address this gap, a cross-sectional study was conducted among people living with HIV (PLHIV) on second-line ART to examine the direct and indirect effects of covariates on internalized stigma. Structural equation modeling (SEM) was employed as the analytical framework to assess these direct and indirect effects of covariates on internalized stigma among PLHIV on second-line ART. Methods Study setting This study was conducted at Dessie and Woldia Comprehensive Specialized Hospitals in northeast Ethiopia from January 13 to April 13, 2025. Located in the southern and northern parts of Wollo in the Amhara region, respectively, these two hospitals serve as the main referral centers for second-line antiretroviral therapy (ART) in the eastern Amhara region. Dessie and Woldia Comprehensive Specialized Hospitals currently provide second-line ART to 624 and 343 people living with HIV (PLHIV), respectively. Study design and period An institutional-based cross-sectional study was conducted among second-line ART users at Dessie and Woldia Comprehensive Specialized Hospitals from January 13 to April 13, 2025. Source and study population The source population for this study consisted of adults receiving second-line antiretroviral therapy at Dessie and Woldia Comprehensive Specialized Hospitals, while the study population included those who were available during the data collection period Variables and measurements The primary outcome variable in this study was internalized stigma, which was measured using eight items from the HIV stigma scale [17, 21]. These items were assessed using a four-point Likert scale (strongly disagree, disagree, agree, and strongly agree), with higher scores indicating higher levels of stigma. The total score for internalized stigma (IS) ranges from 8–32 [3, 17, 21]. While perceived stigma, was measured using six items from the HIV stigma scale [17, 21]. These items were assessed using a four-point Likert scale (strongly disagree, disagree, agree, and strongly agree), with higher scores indicating higher levels of stigma. The total score for perceived stigma (PS) ranges from 6–24 [3, 17, 21]. Social support was measured using the three-item Oslo scale, where one item used a 1–4 point Likert scale, and the other two items used a 1–5 point Likert scale. The total score of Oslo scale ranges from 3 to 14, with higher scores indicating stronger social support [17, 22]. For SEM analysis, the raw social support score was treated as a continuous variable [3, 17, 23]. Furthermore, depression was measured using the nine-item patient health questionnaire (PHQ-9) [17, 24, 25] where participants rated the frequency of depressive symptoms experienced in the past two weeks. Scores range from 0 to 27, with higher scores indicating more frequent symptoms. A score of 0 means no symptoms, while a score of 3 means almost daily symptoms. The PHQ-9 tool has been validated in the Ethiopian context [17, 26, 27]. The socio-demographic characteristics included age, sex, marital status, and independent source of income, while the clinical characteristics included body mass index (BMI), functional status, and WHO clinical stage (Fig. 1 ). Sample size This research builds on my previous project on factors associated with health-related quality of life among second-line ART patients in northeast Ethiopia [28]. Using the rule of 5–20 times the number of free parameters in structural equation modeling, the total free parameters in my previous project were 153[28]. Therefore, the minimum sample size is 765 (153 * 5). Including a 10% nonresponse rate, the final sample size is 841[28]. Sampling procedure A simple random sampling method was used to select participants from ART smart care. The total number of PLHIV on second-line ART at Dessie and Woldia Comprehensive Specialized Hospitals was 624 and 343, respectively. The sample proportion from each hospital was determined, and 543 participants were selected from Dessie and 298 from Woldia. The detail found our previous article [28]. The detail of the of sampling procedure was clear stated in parent article of original project [28]. Data collection Data was collected through document reviews and face-to-face interviews by trained health officers in the ART outpatient department, using an Amharic questionnaire. The detail of the of sampling procedure was clear stated in parent article of original project [28]. Data collection occurred over three months during routine clinical visits, with the data extraction sheet based on national antiretroviral guidelines [17, 29]. Data quality management To ensure data quality, the questionnaire was based on literature and relevant guidelines, using validated tools to measure latent constructs. It was pretested on 5% of participants at Dessie Health Center, and adjustments were made. The detail of the of data quality management was clear stated in parent article of original project [28]. Data collectors received training on the study's objectives and data collection process, with monitoring and onsite feedback from the supervisor and principal investigator to ensure accuracy[17]. Data analysis Data was collected via Kobo Toolbox, cleaned, and analyzed in Stata version 17. Descriptive statistics were presented using means, medians, and frequencies. The detail of the of data analysis was clear stated in parent article of original project [28]. Structural equation modeling (SEM) was used to analyze relationships among variables, with effect sizes expressed as beta coefficients and statistical significance set at P < 0.05. The model was iteratively refined based on fit indices and adjustments were made where necessary. Ethics consideration This study was conducted in accordance with the ethical standards of the institutional research committee and the principles outlined in the Declaration of Helsinki. Before the study began, ethical clearance was obtained from the ethical review committee of the College of Medicine and Health Science, Wollo University [Ref. No- WU/CMHS/0003/20/2025]. Informed verbal consent was obtained from all participants before the interview. Privacy, anonymity, and confidentiality of participants were ensured throughout the study process. Participants were informed that refusing consent or withdrawing from the study would not negatively affect their access to healthcare. Clinical trial number: Not applicable. Results Socio‑demographic characteristics Of 841 eligible patients, 825 (98%) were participated. Most lived in urban areas (75.4%), 49.2% were male, 43.2% were married, 30% had no formal education, and 43% had independent source of income. The median (IQR) ART duration was 5 (3–8) years, and age was 39 (36–49) years (Table 1 ). Table 1 Socio-demographic characteristics of PLHIV on second-line ART at DCSH and WCSH in the eastern Amhara region, northeast Ethiopia, January 2025–April 2025 (n = 825) Socio‑demographic Characteristics Categories Total (825) N (%) median, (IQR) or mean, (SD) Residence Urban 622 (75.39) Rural 203 (24.61) Sex Male 406 (49.21) Female 419 (50.79) Marital status Married 356 (43.15) Single 250 (30.30) Divorced 145 (17.58) Widowed 74 (8.97) Educ. Level No-educated 247 (29.94) Primary 242 (29.33) Secondary 221 (26.79) Tertiary 115 (13.94) Independent source of income Yes 355 (43.03) No 470 (56.97) Age median,(IQR) year 39 (36–49) Dura-second line media,(IQR) year 5 (3–8) DCSH Dessie comprehensive specialized hospital and WCSH Woldia comprehensive specialized hospital Clinical characteristics Of 825 participants, 68.1% had WHO clinical stage one. Viral load was suppressed (< 50 copies/ml) in 85.8%, low (50–999) in 8.7%, and high (≥ 1000) in 5.5%. Additionally, 56% had ≤ 450 cells/mm³ CD4 count, and 64% had BMI ≥ 18.5 kg/m² (Table 2 ). Table 2 Clinical characteristics of PLHIV on second-line antiretroviral therapy at DCSH and WCSH in the eastern Amhara region, northeast Ethiopia, January 2025– April 2025 (n = 825) Clinical characteristics Categories Total (825) N (%) median, (IQR) or mean, (SD) Functional status Workable 779 (94.42) Non-workable 46 (5.58) Medication adherence Optimal adherence 780 (94.55) Not optimal adherence 45 (4.45) Second-line ART administration. TDF-3TC-ATV/r 430 (52.12) AZT-3TC-ATV/r 345 (41.81) TDF-3TC-LPV/r 30 (3.64) AZT-3TC-LPV/r 20 (2.42) Viral load Less than 50 (Suppressed) 708 (85.82) 50 to 999 (low viremia) 72 (8.73) 1000 or more high viremia 45 (5.45) WHO clinical stage WHO stage one 562 (68.12) WHO stage two 184 (22.30) WHO stage three 56 (6.79) WHO stage four 23 (2.79) CD4_cat 0-450 463 (56.12) 451 and above 362 (43.88) Opportunistic infection Yes 108 (13.09) No 717 (86.91) BMI Less than 18.5 296 (35.88) 18.5 and above 529 (64.12) Spearman correlation between social support, perceived stigma, depression and other covariates (n = 825) Depression was positively correlated with viral load and perceived stigma with (r = 0.2 and 0.8 respectively, p-value < 0.001) and negatively correlated with social support with (r = -0.7, p-value < 0.001) (Table 3 ). Table 3 spearman’s rank correlation analysis of depression, social support, perceived stigma, and other covariates, (n = 825). Variable 1. 2. 3. 4. 5. 6. 1. Depression 1 2. Perceived stigma 0.8*** 1 3. Social support -0.7*** -0.7*** 1 4. Viral load 0.2*** 0.2*** -0.2*** 1 5. Body mass index -0.2*** -0.2*** 0.2*** -0.09** 1 6. Internalized stigma 0.77*** 0.82** -0.78*** 0.2*** -0.19*** 1 Dep depression, PS perceived stigma, SS social support, VL viral load, BMI body mass index Measurement model Confirmatory factor analysis (CFA) showed that all the factor loadings of depression, perceived stigma, internalized stigma and social support variables were statistically significant at a P-value less than 0.001. In addition, an evaluation CFI, SRMR, TLI and RMSEA of model fitness was made. And it revealed that the final model was a good fit at a comparative fit index (CFI) = 0.97, root mean square error of approximation (RMSEA) = 0.045, Standardized root mean square residual (SRMR) = 0.022 and TLI = 0.97 (Fig. 2 ). Structural model The structural equation modeling analysis of this study show that all goodness fit test were fit well. The goodness of fit test for comparative fit index (CFI), Root mean squared error of approximation (RMSEA), Standardized root mean squared residual (SRMR) and Tucker–Lewis index (TLI) were 0.946, 0.062, 0.064 and 0.940, respectively (Fig. 3 ). Direct and indirect factors associated with internalized stigma Depression has direct positive effect on internalized stigma. The direct effect of depression on internalized stigma was as one unit increase in depression score, internalized stigma score of patients' increase by 0.19 holding the effect of other covariates in the model remain unchanged [ \(\:\widehat{\beta\:}\) = 0.19, (95% CI: 0.111–0.260)]. Moreover, depression moderated the effect of social support on internalized stigma [ \(\:\widehat{\beta\:}\) = -0.16, (95% CI: -0.227 to -0.097)]. Similarly, perceived stigma has direct positive effect on internalized stigma. The direct effect of perceived stigma on internalized stigma was that as perceived stigma score increase by one unit, internalized stigma of patients' increase by 0.92 provided that the effect of other variables in the model remain constant [ \(\:\widehat{\beta\:}\) = 0.92, (95% CI: 0.806–1.042)]. Furthermore, perceived stigma moderate the effect of social support on internalized stigma [ \(\:\widehat{\beta\:}\) = -0.64, (95% CI: -0.72 to -0.552)] (Table 4 ). Table 4 Direct and indirect factors associated with internalized stigma among PLHIV on second-line antiretroviral therapy in northeast Ethiopia (n = 825) 2025. Predictors Estimates ( \(\:\widehat{\varvec{\beta\:}}\) ) SE of \(\:\:\widehat{\varvec{\beta\:}}\) Standardized Estimate 95% CI for Estimates Internalized stigma Direct effect PSS → ISS 0.92 0. 06 0.82 0.806–1.042 DEP → ISS Indirect effect 0.19 0.038 0.20 0.111–0.260 SSS → PSS → ISS -0.64 0.042 -0.634 -0.72 to -0.552 SSS → DEP → ISS -0.16 0.033 -0.162 -0.227 to -0.097 The total effect SSS → ISS -0.80 0.033 -0.797 -0.862 to -0.732 DEP depression, SSS social support score, PSS perceived stigma score and ISS internalized stigma score. Discussion The purpose of this study was to determine direct and indirect factors associated with internalized stigma among PLHIV on second-line ART in northeast Ethiopia. Social support, depression and perceived stigma were significant predictors of internalized stigma among PLHIV on second-line ART. Social support was indirect predictor of internalized stigma through mediated by depression and perceived stigma. In addition, depression and perceived stigmas were direct predictors of internalized stigma and mediates the association between social support and internalized stigma. Moreover, this finding suggests that perceived stigma and depression function as independent mediators, highlighting a parallel and full mediation effect in the association between social support and internalized stigma. The likelihood of internalized stigma was found to be negatively related to social support. This association is supported by prior literature [17, 30, 31]. A possible explanation for this relationship is that as individuals receive more social support, their feelings of shame, guilt, or worthlessness associated with living with HIV may diminish [8, 17, 31]. Moreover, social support whether emotional, informational, or practical can provide a sense of acceptance, belonging, and reassurance, which helps buffer against negative self-perceptions[32]. Furthermore, it allows people living with HIV to feel understood, valued, and less isolated, which in turn reduces the tendency to internalize societal stigma [30, 33, 34]. Furthermore, when patients are surrounded by supportive networks, they are more likely to disclose their status, access care, and engage in open conversations, all of which can foster positive identity reconstruction and resilience against internalized stigma [17, 18, 35, 36]. Overall, the findings suggest that social support is crucial in preventing mental health issues. Therefore, promoting support from family and friends should be a priority both within communities and in healthcare settings. Depression was another significant predictor of internalized stigma, showing a positive correlation with the outcome variable internalized stigma. Individuals experiencing depression may be more likely to internalize negative societal attitudes toward HIV, leading to heightened feelings of shame, worthlessness, and self-blame [17, 30, 31]. This psychological mechanism can explain why depression is strongly linked with internalized stigma [17, 19]. This association is also supported by existing literature[30, 37]. In addition, this study underscores the mediating role of depression in the link between social support and internalized stigma. This finding indicates that inadequate social support may elevate the risk of depression, which subsequently contributes to greater internalized stigma. This implies that social support may help protect against stigma indirectly by alleviating depressive symptoms. Consequently, integrating mental health services such as routine depression screening and focused psychosocial interventions into standard HIV care is essential to reduce internalized stigma among individuals on second-line antiretroviral therapy[19, 38]. Perceived stigma was positively correlated with internalized stigma, which is consistent with prior research findings [19, 38]. The observed positive relationship between perceived stigma and internalized stigma may stem from the tendency of individuals who regularly face or expect negative societal reactions to absorb these attitudes. As a result, they may begin to adopt these external judgments as part of their self-image, which can lead to increased feelings of shame, self-blame, and reduced self-esteem and this association has been supported by prior research [39, 40]. Overall, a key contribution of this study lies in identifying both parallel and complete mediation effects in the relationship between social support and internalized stigma. Specifically, the findings revealed that depression and perceived stigma independently mediated this association, highlighting distinct psychological pathways through which limited social support can lead to greater internalized stigma among PLHIV on second-line ART. Strength and limitation of the study First, this is the first study in Ethiopia to investigate both direct and indirect factors influencing internalized stigma among PLHIV on second-line ART. Second, it employed structural equation modeling, allowing for the simultaneous estimation of complex relationships while accounting for measurement errors in latent variables. Third, the study used a large sample size, enhancing the robustness of the findings. Lastly, the results are relevant to other low-income settings that follow similar WHO HIV treatment guidelines. First, the use of self-reported data for most latent constructs may introduce biases such as social desirability biases, potentially affecting data accuracy. Second, the cross-sectional design limits causal inference, making it difficult to determine the directionality of associations. Conclusion This finding suggests that perceived stigma and depression fully mediate the relationship between social support and internalized stigma among PLHIV on second-line ART. Moreover, perceived stigma and depression functioned as parallel mediators in the relationship between social support and internalized stigma while also having a direct positive effect on internalized stigma. Social support, perceived stigmas and depression were significance predictors of internalized stigma. Therefore, healthcare facilities should incorporate and reinforce routine mental health screenings and interventions within HIV care programs, acknowledging the substantial effect of perceived stigma, social support and depression on internalized stigma among second-line ART patients. Moreover, early identification and management of depression, along with efforts to mitigate perceived stigma while strengthening social support, are highly recommended. Abbreviations IS Internalized stigma OSSS-3 Oslo Social Support Scale-3 PLHIV people with human immunodeficiency virus SEM Structural equation modeling PHQ-9 Patient Health Questionnaire-9 ART Antiretroviral Therapy BMI Body mass index HAART Highly active antiretroviral therapy HRQoL Health-Related Quality of Life PS Perceived stigma QOL Quality of Life WHO World Health Organization Declarations Ethics approval and consent to participate This study was conducted in accordance with the ethical standards of the institutional research committee and the principles outlined in the Declaration of Helsinki. Before the study began, ethical clearance was obtained from the ethical review committee of the College of Medicine and Health Science, Wollo University [Ref. No- WU/CMHS/0003/20/2025]. Informed verbal consent was obtained from all participants before the interview. Participants were informed that refusing consent or withdrawing from the study would not negatively affect their access to healthcare. Consent for publication Not applicable. Conflict of interest This research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors Author Contribution Keleb Takele Tiruneh , Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing, Ziyin Worku 2 : Conceptualization, Data curation, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing – review & editing, Acknowledgments The authors are grateful to all the data collectors, supervisors, study participants, and Wollo University for their creditable contributions to the success of this study. The authors would also like to thank the Dessie comprehensive specialised hospital and Woldia comprehensive specialised hospital for their open contributions to the success of this research. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8907378","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":597807122,"identity":"7e5d8f8c-c4a3-4028-bd77-a968eecb7dcb","order_by":0,"name":"Keleb Takele Tiruneh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIie3QMUvEMBTA8ZTA3RK4NaWgXyFSyBTaD+LyQqFOgm4HHlxKIV0E1/sSrs45At5S7Hrg0iI4Ky4FF9NbpfXcBPNfGsr78UgQ8vn+YBRhhd2XoTma98CEOweFmSaBI+CIg7Rd5gNRx5Owre3h7yQJq6J4ue6TeIGxYVI3yX1l3ZaVOB8jEdmW8QYyHpYzAKmfs4daOvKYX6oRckKljghgwSxhZiDcOBIoO05Ou+qTwFqkdvGupH7KeNNNk4gGGhOwnGHinqE2Cd//sCW8lWW0yXcxtTOOYJkB37stMHEXurPbjytxc3ZXla9Bz5KUNxdd+7YSo+Rb8jAJx44Ppb8Z9vl8vv/RF5n2YiTN/2IzAAAAAElFTkSuQmCC","orcid":"","institution":"Wollo University","correspondingAuthor":true,"prefix":"","firstName":"Keleb","middleName":"Takele","lastName":"Tiruneh","suffix":""},{"id":597807124,"identity":"85cd22c9-5c82-4729-9118-14cc88bec266","order_by":1,"name":"Ziyin Worku","email":"","orcid":"","institution":"Wollo University","correspondingAuthor":false,"prefix":"","firstName":"Ziyin","middleName":"","lastName":"Worku","suffix":""}],"badges":[],"createdAt":"2026-02-18 08:39:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8907378/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8907378/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104399600,"identity":"e47c81e0-69f1-44a3-8a3b-17a31f322d0b","added_by":"auto","created_at":"2026-03-11 12:06:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":65210,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConceptual framework\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ea hypothesized model for Structural Equation Modeling of Depression, Stigma, and Social Support among People Living with HIV on Second-Line ART in Northeast Ethiopia: A Cross-Sectional Study (oval and rectangular shape variables represent latent and observed variables, respectively). (DEP depression, SSS social support score, PSS perceived stigma score, ISS internalized stigma score and BMI body mass index).\u003c/p\u003e\n\u003cp\u003eThis A hypothesized model was based on literature [4, 5, 10, 17, 20].\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8907378/v1/03da80d040fe9bef849be352.jpg"},{"id":103627182,"identity":"63014799-ee7c-41a6-9a10-43ac8d48ce6a","added_by":"auto","created_at":"2026-02-27 20:56:28","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":116371,"visible":true,"origin":"","legend":"\u003cp\u003eResults of a standardized factor loadings of a measurement model for the depression, social support perceived and internalized stigma among PLHIV on second-line ART northeast Ethiopia (DEP depression, SS social support, IS internalized stigma score. PS perceived stigma score).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8907378/v1/148226beee5ece22e92f59c9.jpg"},{"id":103627180,"identity":"592b1e0f-77c8-43b5-b41a-37ac0ccb848a","added_by":"auto","created_at":"2026-02-27 20:56:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":107978,"visible":true,"origin":"","legend":"\u003cp\u003eStructural equation modeling of direct and indirect factors associated with internalized stigma among people living with HIV on second-line antiretroviral therapy in northeast Ethiopia. (DEP depression, SSS social support score, ISS internalized stigma score. PSS perceived stigma score).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8907378/v1/9fcb6ea9aa04fb9fc9183ca6.jpg"},{"id":104407736,"identity":"9cb19a55-7852-4db7-b48d-ad2164929f7e","added_by":"auto","created_at":"2026-03-11 12:39:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1314537,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8907378/v1/534ae10d-10d0-4fe1-a3f9-9fbd14234ba2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Structural Equation Modeling of Depression, Stigma, and Social Support among People Living with HIV on Second-Line ART in Northeast Ethiopia: A Cross-Sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHIV/AIDS remains a major global public health challenge, with sub-Saharan Africa (SSA) bearing the highest burden, accounting for over two-thirds of all reported cases[1]. The global availability of HIV treatment medications is a significant advancement in achieving USAID\u0026rsquo;s 90-90-90 targets [2, 3]. Due to the effectiveness of combination antiretroviral therapy (ART), people living with HIV (PLWH) can achieve life expectancies close to those of the general population[4]. Although ART has increased the life expectancy of people living with HIV (PLWH), they still face various health challenges, including opportunistic infections, syphilis, tuberculosis, and widespread HIV-related stigma [3, 5]. Furthermore, HIV/AIDS continues to be a major barrier to Ethiopia's overall development, contributing to a seven-year reduction in life expectancy and a significant decline in the workforce [6].\u003c/p\u003e \u003cp\u003eStigma forces individuals to hide their HIV status, discourages medical visits, hinders medication adherence, and restricts access to social support [7, 8]. HIV stigma refers to the process in which people living with HIV (PLWH) are socially discredited and devalued due to their HIV status [4, 9, 10]. Furthermore, stigma was traditionally defined as \u0026ldquo;a significantly discrediting trait\u0026rdquo; and later broadened to mean \u0026ldquo;a powerful discrediting and tainting social label that fundamentally alters how individuals perceive themselves and how they are perceived by others\u0026rdquo; [3, 11, 12]. Additionally, individuals diagnosed with HIV/AIDS may face stigma because the modes of HIV transmission are often perceived as controllable, along with the associated HIV-related risk behaviors [3, 13]. Moreover, because HIV/AIDS is viewed as a degenerative and incurable disease, people may harbor fears such as fear of the disease, contagion, and death towards those living with HIV, which can result in widespread stigma [3, 8, 14]. On the other hand, people living with HIV (PLWH) who perceive themselves as responsible for their own actions are more likely to experience intense feelings of shame and guilt [4, 8, 15].\u003c/p\u003e \u003cp\u003ePerceived and internalized stigma (PIS) encompasses two significant forms of stigma that are common among people living with HIV (PLWH) and are closely linked to mental and behavioral health [3, 4, 8, 16\u0026ndash;18]. Perceived HIV-related stigma is defined as the recognition of discriminatory and prejudicial attitudes directed towards individuals by members of society [17, 18]. Furthermore, individuals who internalize stigma tend to develop negative beliefs and self-images, often accompanied by low self-esteem, due to adopting the negative perceptions held by society [3, 7]. Individuals who perceive stigma from others in society are often vulnerable to feelings of self-hatred, particularly when they internalize society's negative views of themselves [7, 17]. As a result, the combined effects of perceived and internalized stigma can lead to various consequences, including non-disclosure of HIV status, social isolation, and depressive symptoms [4, 17, 19].\u003c/p\u003e \u003cp\u003eAlthough internalized stigma is influenced by depression, social support, and perceived stigma both directly and indirectly, there is no literature within the Ethiopian context that determines the direct and indirect effects of these covariates on internalized stigma among people living with HIV (PLHIV) on second-line ART. While some studies have attempted to measure internalized stigma, these publications have treated it as a predictor variable rather than determining it as a latent outcome variable, and they fail to account for measurement error in the latent construct.\u003c/p\u003e \u003cp\u003eTo address this gap, a cross-sectional study was conducted among people living with HIV (PLHIV) on second-line ART to examine the direct and indirect effects of covariates on internalized stigma. Structural equation modeling (SEM) was employed as the analytical framework to assess these direct and indirect effects of covariates on internalized stigma among PLHIV on second-line ART.\u003c/p\u003e"},{"header":"Methods","content":" \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003eStudy setting\u003c/h2\u003e \u003cp\u003eThis study was conducted at Dessie and Woldia Comprehensive Specialized Hospitals in northeast Ethiopia from January 13 to April 13, 2025. Located in the southern and northern parts of Wollo in the Amhara region, respectively, these two hospitals serve as the main referral centers for second-line antiretroviral therapy (ART) in the eastern Amhara region. Dessie and Woldia Comprehensive Specialized Hospitals currently provide second-line ART to 624 and 343 people living with HIV (PLHIV), respectively.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eStudy design and period\u003c/h3\u003e\n\u003cp\u003eAn institutional-based cross-sectional study was conducted among second-line ART users at Dessie and Woldia Comprehensive Specialized Hospitals from January 13 to April 13, 2025.\u003c/p\u003e\n\u003ch3\u003eSource and study population\u003c/h3\u003e\n\u003cp\u003eThe source population for this study consisted of adults receiving second-line antiretroviral therapy at Dessie and Woldia Comprehensive Specialized Hospitals, while the study population included those who were available during the data collection period\u003c/p\u003e\n\u003ch3\u003eVariables and measurements\u003c/h3\u003e\n\u003cp\u003eThe primary outcome variable in this study was internalized stigma, which was measured using eight items from the HIV stigma scale [17, 21]. These items were assessed using a four-point Likert scale (strongly disagree, disagree, agree, and strongly agree), with higher scores indicating higher levels of stigma. The total score for internalized stigma (IS) ranges from 8\u0026ndash;32 [3, 17, 21]. While perceived stigma, was measured using six items from the HIV stigma scale [17, 21]. These items were assessed using a four-point Likert scale (strongly disagree, disagree, agree, and strongly agree), with higher scores indicating higher levels of stigma. The total score for perceived stigma (PS) ranges from 6\u0026ndash;24 [3, 17, 21].\u003c/p\u003e \u003cp\u003eSocial support was measured using the three-item Oslo scale, where one item used a 1\u0026ndash;4 point Likert scale, and the other two items used a 1\u0026ndash;5 point Likert scale. The total score of Oslo scale ranges from 3 to 14, with higher scores indicating stronger social support [17, 22]. For SEM analysis, the raw social support score was treated as a continuous variable [3, 17, 23]. Furthermore, depression was measured using the nine-item patient health questionnaire (PHQ-9) [17, 24, 25] where participants rated the frequency of depressive symptoms experienced in the past two weeks. Scores range from 0 to 27, with higher scores indicating more frequent symptoms. A score of 0 means no symptoms, while a score of 3 means almost daily symptoms. The PHQ-9 tool has been validated in the Ethiopian context [17, 26, 27].\u003c/p\u003e \u003cp\u003eThe socio-demographic characteristics included age, sex, marital status, and independent source of income, while the clinical characteristics included body mass index (BMI), functional status, and WHO clinical stage (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSample size\u003c/h2\u003e \u003cp\u003eThis research builds on my previous project on factors associated with health-related quality of life among second-line ART patients in northeast Ethiopia [28]. Using the rule of 5\u0026ndash;20 times the number of free parameters in structural equation modeling, the total free parameters in my previous project were 153[28]. Therefore, the minimum sample size is 765 (153 * 5). Including a 10% nonresponse rate, the final sample size is 841[28].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSampling procedure\u003c/h3\u003e\n\u003cp\u003eA simple random sampling method was used to select participants from ART smart care. The total number of PLHIV on second-line ART at Dessie and Woldia Comprehensive Specialized Hospitals was 624 and 343, respectively. The sample proportion from each hospital was determined, and 543 participants were selected from Dessie and 298 from Woldia. The detail found our previous article [28]. The detail of the of sampling procedure was clear stated in parent article of original project [28].\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eData was collected through document reviews and face-to-face interviews by trained health officers in the ART outpatient department, using an Amharic questionnaire. The detail of the of sampling procedure was clear stated in parent article of original project [28]. Data collection occurred over three months during routine clinical visits, with the data extraction sheet based on national antiretroviral guidelines [17, 29].\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eData quality management\u003c/h2\u003e \u003cp\u003e To ensure data quality, the questionnaire was based on literature and relevant guidelines, using validated tools to measure latent constructs. It was pretested on 5% of participants at Dessie Health Center, and adjustments were made. The detail of the of data quality management was clear stated in parent article of original project [28]. Data collectors received training on the study's objectives and data collection process, with monitoring and onsite feedback from the supervisor and principal investigator to ensure accuracy[17].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eData was collected via Kobo Toolbox, cleaned, and analyzed in Stata version 17. Descriptive statistics were presented using means, medians, and frequencies. The detail of the of data analysis was clear stated in parent article of original project [28]. Structural equation modeling (SEM) was used to analyze relationships among variables, with effect sizes expressed as beta coefficients and statistical significance set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The model was iteratively refined based on fit indices and adjustments were made where necessary.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEthics consideration\u003c/h2\u003e \u003cp\u003e This study was conducted in accordance with the ethical standards of the institutional research committee and the principles outlined in the Declaration of Helsinki. Before the study began, ethical clearance was obtained from the ethical review committee of the College of Medicine and Health Science, Wollo University [Ref. No- WU/CMHS/0003/20/2025]. Informed verbal consent was obtained from all participants before the interview. Privacy, anonymity, and confidentiality of participants were ensured throughout the study process. Participants were informed that refusing consent or withdrawing from the study would not negatively affect their access to healthcare. \u003cb\u003eClinical trial number: Not applicable.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003eSocio‑demographic characteristics\u003c/h2\u003e \u003cp\u003eOf 841 eligible patients, 825 (98%) were participated. Most lived in urban areas (75.4%), 49.2% were male, 43.2% were married, 30% had no formal education, and 43% had independent source of income. The median (IQR) ART duration was 5 (3\u0026ndash;8) years, and age was 39 (36\u0026ndash;49) years (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSocio-demographic characteristics of PLHIV on second-line ART at DCSH and WCSH in the eastern Amhara region, northeast Ethiopia, January 2025\u0026ndash;April 2025 (n\u0026thinsp;=\u0026thinsp;825)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocio‑demographic Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal (825) N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003emedian, (IQR) or mean, (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eResidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e622 (75.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRural\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e203 (24.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e406 (49.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e419 (50.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eMarital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e356 (43.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e250 (30.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDivorced\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e145 (17.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWidowed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74 (8.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eEduc. Level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo-educated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e247 (29.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e242 (29.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e221 (26.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTertiary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e115 (13.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndependent source of income\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e355 (43.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e470 (56.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge median,(IQR) year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (36\u0026ndash;49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDura-second line media,(IQR) year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (3\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDCSH Dessie comprehensive specialized hospital and WCSH Woldia comprehensive specialized hospital\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical characteristics\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOf 825 participants, 68.1% had WHO clinical stage one. Viral load was suppressed (\u0026lt;\u0026thinsp;50 copies/ml) in 85.8%, low (50\u0026ndash;999) in 8.7%, and high (\u0026ge;\u0026thinsp;1000) in 5.5%. Additionally, 56% had\u0026thinsp;\u0026le;\u0026thinsp;450 cells/mm\u0026sup3; CD4 count, and 64% had BMI\u0026thinsp;\u0026ge;\u0026thinsp;18.5 kg/m\u0026sup2; (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of PLHIV on second-line antiretroviral therapy at DCSH and WCSH in the eastern Amhara region, northeast Ethiopia, January 2025\u0026ndash; April 2025 (n\u0026thinsp;=\u0026thinsp;825)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal (825) N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003emedian, (IQR) or mean, (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFunctional status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWorkable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e779 (94.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-workable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46 (5.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMedication adherence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOptimal adherence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e780 (94.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot optimal adherence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45 (4.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eSecond-line ART administration.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTDF-3TC-ATV/r\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e430 (52.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAZT-3TC-ATV/r\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e345 (41.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTDF-3TC-LPV/r\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (3.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAZT-3TC-LPV/r\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eViral load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLess than 50 (Suppressed)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e708 (85.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 to 999 (low viremia)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72 (8.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1000 or more high viremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45 (5.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eWHO clinical stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWHO stage one\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e562 (68.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWHO stage two\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e184 (22.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWHO stage three\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56 (6.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWHO stage four\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCD4_cat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e463 (56.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e451 and above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e362 (43.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOpportunistic infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108 (13.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e717 (86.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLess than 18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e296 (35.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.5 and above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e529 (64.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eSpearman correlation between social support, perceived stigma, depression and other covariates (n\u0026thinsp;=\u0026thinsp;825)\u003c/h2\u003e \u003cp\u003eDepression was positively correlated with viral load and perceived stigma with (r\u0026thinsp;=\u0026thinsp;0.2 and 0.8 respectively, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and negatively correlated with social support with (r = -0.7, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003espearman\u0026rsquo;s rank correlation analysis of depression, social support, perceived stigma, and other covariates, (n\u0026thinsp;=\u0026thinsp;825).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1. Depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2. Perceived stigma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3. Social support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.7***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.7***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4. Viral load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5. Body mass index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.09**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6. Internalized stigma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.77***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.82**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.78***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.19***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDep depression, PS perceived stigma, SS social support, VL viral load, BMI body mass index\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement model\u003c/h2\u003e \u003cp\u003eConfirmatory factor analysis (CFA) showed that all the factor loadings of depression, perceived stigma, internalized stigma and social support variables were statistically significant at a P-value less than 0.001. In addition, an evaluation CFI, SRMR, TLI and RMSEA of model fitness was made. And it revealed that the final model was a good fit at a comparative fit index (CFI)\u0026thinsp;=\u0026thinsp;0.97, root mean square error of approximation (RMSEA)\u0026thinsp;=\u0026thinsp;0.045, Standardized root mean square residual (SRMR)\u0026thinsp;=\u0026thinsp;0.022 and TLI\u0026thinsp;=\u0026thinsp;0.97 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eStructural model\u003c/h2\u003e \u003cp\u003eThe structural equation modeling analysis of this study show that all goodness fit test were fit well. The goodness of fit test for comparative fit index (CFI), Root mean squared error of approximation (RMSEA), Standardized root mean squared residual (SRMR) and Tucker\u0026ndash;Lewis index (TLI) were 0.946, 0.062, 0.064 and 0.940, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eDirect and indirect factors associated with internalized stigma\u003c/h2\u003e \u003cp\u003eDepression has direct positive effect on internalized stigma. The direct effect of depression on internalized stigma was as one unit increase in depression score, internalized stigma score of patients' increase by 0.19 holding the effect of other covariates in the model remain unchanged [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = 0.19, (95% CI: 0.111\u0026ndash;0.260)]. Moreover, depression moderated the effect of social support on internalized stigma [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = -0.16, (95% CI: -0.227 to -0.097)].\u003c/p\u003e \u003cp\u003eSimilarly, perceived stigma has direct positive effect on internalized stigma. The direct effect of perceived stigma on internalized stigma was that as perceived stigma score increase by one unit, internalized stigma of patients' increase by 0.92 provided that the effect of other variables in the model remain constant [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = 0.92, (95% CI: 0.806\u0026ndash;1.042)]. Furthermore, perceived stigma moderate the effect of social support on internalized stigma [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = -0.64, (95% CI: -0.72 to -0.552)] (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDirect and indirect factors associated with internalized stigma among PLHIV on second-line antiretroviral therapy in northeast Ethiopia (n\u0026thinsp;=\u0026thinsp;825) 2025.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEstimates (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\varvec{\\beta\\:}}\\)\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE of\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\:\\widehat{\\varvec{\\beta\\:}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandardized Estimate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% CI for Estimates\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eInternalized stigma\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eDirect effect\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSS \u0026rarr; ISS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0. 06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.806\u0026ndash;1.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDEP \u0026rarr; ISS\u003c/p\u003e \u003cp\u003e\u003cb\u003eIndirect effect\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.111\u0026ndash;0.260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSSS \u0026rarr; PSS \u0026rarr; ISS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.634\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.72 to -0.552\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSSS \u0026rarr; DEP \u0026rarr; ISS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.227 to -0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe total effect\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSSS \u0026rarr; ISS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.797\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.862 to -0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDEP depression, SSS social support score, PSS perceived stigma score and ISS internalized stigma score.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe purpose of this study was to determine direct and indirect factors associated with internalized stigma among PLHIV on second-line ART in northeast Ethiopia. Social support, depression and perceived stigma were significant predictors of internalized stigma among PLHIV on second-line ART. Social support was indirect predictor of internalized stigma through mediated by depression and perceived stigma. In addition, depression and perceived stigmas were direct predictors of internalized stigma and mediates the association between social support and internalized stigma. Moreover, this finding suggests that perceived stigma and depression function as independent mediators, highlighting a parallel and full mediation effect in the association between social support and internalized stigma.\u003c/p\u003e \u003cp\u003eThe likelihood of internalized stigma was found to be negatively related to social support. This association is supported by prior literature [17, 30, 31]. A possible explanation for this relationship is that as individuals receive more social support, their feelings of shame, guilt, or worthlessness associated with living with HIV may diminish [8, 17, 31]. Moreover, social support whether emotional, informational, or practical can provide a sense of acceptance, belonging, and reassurance, which helps buffer against negative self-perceptions[32]. Furthermore, it allows people living with HIV to feel understood, valued, and less isolated, which in turn reduces the tendency to internalize societal stigma [30, 33, 34]. Furthermore, when patients are surrounded by supportive networks, they are more likely to disclose their status, access care, and engage in open conversations, all of which can foster positive identity reconstruction and resilience against internalized stigma [17, 18, 35, 36]. Overall, the findings suggest that social support is crucial in preventing mental health issues. Therefore, promoting support from family and friends should be a priority both within communities and in healthcare settings.\u003c/p\u003e \u003cp\u003eDepression was another significant predictor of internalized stigma, showing a positive correlation with the outcome variable internalized stigma. Individuals experiencing depression may be more likely to internalize negative societal attitudes toward HIV, leading to heightened feelings of shame, worthlessness, and self-blame [17, 30, 31]. This psychological mechanism can explain why depression is strongly linked with internalized stigma [17, 19]. This association is also supported by existing literature[30, 37]. In addition, this study underscores the mediating role of depression in the link between social support and internalized stigma. This finding indicates that inadequate social support may elevate the risk of depression, which subsequently contributes to greater internalized stigma. This implies that social support may help protect against stigma indirectly by alleviating depressive symptoms. Consequently, integrating mental health services such as routine depression screening and focused psychosocial interventions into standard HIV care is essential to reduce internalized stigma among individuals on second-line antiretroviral therapy[19, 38].\u003c/p\u003e \u003cp\u003ePerceived stigma was positively correlated with internalized stigma, which is consistent with prior research findings [19, 38]. The observed positive relationship between perceived stigma and internalized stigma may stem from the tendency of individuals who regularly face or expect negative societal reactions to absorb these attitudes. As a result, they may begin to adopt these external judgments as part of their self-image, which can lead to increased feelings of shame, self-blame, and reduced self-esteem and this association has been supported by prior research [39, 40]. Overall, a key contribution of this study lies in identifying both parallel and complete mediation effects in the relationship between social support and internalized stigma. Specifically, the findings revealed that depression and perceived stigma independently mediated this association, highlighting distinct psychological pathways through which limited social support can lead to greater internalized stigma among PLHIV on second-line ART.\u003c/p\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eStrength and limitation of the study\u003c/h2\u003e \u003cp\u003eFirst, this is the first study in Ethiopia to investigate both direct and indirect factors influencing internalized stigma among PLHIV on second-line ART. Second, it employed structural equation modeling, allowing for the simultaneous estimation of complex relationships while accounting for measurement errors in latent variables. Third, the study used a large sample size, enhancing the robustness of the findings. Lastly, the results are relevant to other low-income settings that follow similar WHO HIV treatment guidelines.\u003c/p\u003e \u003cp\u003eFirst, the use of self-reported data for most latent constructs may introduce biases such as social desirability biases, potentially affecting data accuracy. Second, the cross-sectional design limits causal inference, making it difficult to determine the directionality of associations.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis finding suggests that perceived stigma and depression fully mediate the relationship between social support and internalized stigma among PLHIV on second-line ART. Moreover, perceived stigma and depression functioned as parallel mediators in the relationship between social support and internalized stigma while also having a direct positive effect on internalized stigma. Social support, perceived stigmas and depression were significance predictors of internalized stigma. Therefore, healthcare facilities should incorporate and reinforce routine mental health screenings and interventions within HIV care programs, acknowledging the substantial effect of perceived stigma, social support and depression on internalized stigma among second-line ART patients. Moreover, early identification and management of depression, along with efforts to mitigate perceived stigma while strengthening social support, are highly recommended.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternalized stigma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOSSS-3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOslo Social Support Scale-3\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePLHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epeople with human immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSEM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStructural equation modeling\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePHQ-9\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatient Health Questionnaire-9\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntiretroviral Therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHAART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHighly active antiretroviral therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHRQoL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHealth-Related Quality of Life\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePerceived stigma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eQOL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eQuality of Life\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThis study was conducted in accordance with the ethical standards of the institutional research committee and the principles outlined in the Declaration of Helsinki. Before the study began, ethical clearance was obtained from the ethical review committee of the College of Medicine and Health Science, Wollo University [Ref. No- WU/CMHS/0003/20/2025]. Informed verbal consent was obtained from all participants before the interview. Participants were informed that refusing consent or withdrawing from the study would not negatively affect their access to healthcare.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eThis research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKeleb Takele Tiruneh , Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing, Ziyin Worku 2 : Conceptualization, Data curation, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing \u0026ndash; review \u0026amp; editing,\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors are grateful to all the data collectors, supervisors, study participants, and Wollo University for their creditable contributions to the success of this study. The authors would also like to thank the Dessie comprehensive specialised hospital and Woldia comprehensive specialised hospital for their open contributions to the success of this research.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe original contributions of this article are directed to be addressed by the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePhillips, J.A.J.W.H. and Safety, \u003cem\u003eHIV and Workers.\u003c/em\u003e 2021. \u003cb\u003e69\u003c/b\u003e(11): p. 541–541.\u003c/li\u003e\n\u003cli\u003eTegegne, A.S., \u003cem\u003eQuality of Life and Associated Factors of HIV Patients Under Treatment with First Line Regimens in Public Hospitals in Amhara Region, North-West Ethiopia.\u003c/em\u003e Patient Prefer Adherence, 2023. \u003cb\u003e17\u003c/b\u003e: p. 1347–1359.\u003c/li\u003e\n\u003cli\u003eZeng, C., et al., \u003cem\u003eA structural equation model of perceived and internalized stigma, depression, and suicidal status among people living with HIV/AIDS.\u003c/em\u003e BMC Public Health, 2018. \u003cb\u003e18\u003c/b\u003e(1): p. 138.\u003c/li\u003e\n\u003cli\u003eCamacho, G., et al., \u003cem\u003eAnticipated HIV-related stigma and HIV treatment adherence: the indirect effect of medication concerns.\u003c/em\u003e 2020. \u003cb\u003e24\u003c/b\u003e: p. 185–191.\u003c/li\u003e\n\u003cli\u003eMa, Y., et al., \u003cem\u003eThe human immunodeficiency virus care continuum in China: 1985–2015.\u003c/em\u003e 2018. \u003cb\u003e66\u003c/b\u003e(6): p. 833–839.\u003c/li\u003e\n\u003cli\u003eTesfay, A., et al., \u003cem\u003eGender differences in health related quality of life among people living with HIV on highly active antiretroviral therapy in Mekelle Town, Northern Ethiopia.\u003c/em\u003e Biomed Res Int, 2015. \u003cb\u003e2015\u003c/b\u003e: p. 516369.\u003c/li\u003e\n\u003cli\u003eKatz, I.T., et al., \u003cem\u003eImpact of HIV-related stigma on treatment adherence: systematic review and meta‐synthesis.\u003c/em\u003e 2013. \u003cb\u003e16\u003c/b\u003e: p. 18640.\u003c/li\u003e\n\u003cli\u003eNguyen, V.H.A., et al., \u003cem\u003eThe interplay of psychological distress, stigma, and social support in determining quality of life among Vietnamese people living with HIV.\u003c/em\u003e 2025. \u003cb\u003e5\u003c/b\u003e(1): p. 1–11.\u003c/li\u003e\n\u003cli\u003eEarnshaw, V.A., S.R.J.A. 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Triandis, \u003cem\u003eIndividualism-collectivism: A study of cross-cultural researchers.\u003c/em\u003e 1986. \u003cb\u003e17\u003c/b\u003e(2): p. 225–248.\u003c/li\u003e\n\u003cli\u003eWedajo, S., et al., \u003cem\u003eSocial support, perceived stigma, and depression among PLHIV on second-line antiretroviral therapy using structural equation modeling in a multicenter study in Northeast Ethiopia.\u003c/em\u003e Int J Ment Health Syst, 2022. \u003cb\u003e16\u003c/b\u003e(1): p. 27.\u003c/li\u003e\n\u003cli\u003eHong, Y., et al., \u003cem\u003eSelf-perceived stigma, depressive symptoms, and suicidal behaviors among female sex workers in China.\u003c/em\u003e 2010. \u003cb\u003e21\u003c/b\u003e(1): p. 29–34.\u003c/li\u003e\n\u003cli\u003eZeng, C., et al., \u003cem\u003eA structural equation model of perceived and internalized stigma, depression, and suicidal status among people living with HIV/AIDS.\u003c/em\u003e 2018. \u003cb\u003e18\u003c/b\u003e: p. 1–11.\u003c/li\u003e\n\u003cli\u003eStangl, A.L., et al., \u003cem\u003eThe Health Stigma and Discrimination Framework: a global, crosscutting framework to inform research, intervention development, and policy on health-related stigmas.\u003c/em\u003e 2019. \u003cb\u003e17\u003c/b\u003e: p. 1–13.\u003c/li\u003e\n\u003cli\u003eDalgard, O.S., et al., \u003cem\u003eNegative life events, social support and gender difference in depression: a multinational community survey with data from the ODIN study.\u003c/em\u003e 2006. \u003cb\u003e41\u003c/b\u003e: p. 444–451.\u003c/li\u003e\n\u003cli\u003eDalgard, O.S., et al., \u003cem\u003eNegative life events, social support and gender difference in depression.\u003c/em\u003e Social Psychiatry and Psychiatric Epidemiology, 2006. \u003cb\u003e41\u003c/b\u003e(6): p. 444–451.\u003c/li\u003e\n\u003cli\u003eKocalevent, R.D., et al., \u003cem\u003eSocial support in the general population: standardization of the Oslo social support scale (OSSS-3).\u003c/em\u003e BMC Psychol, 2018. \u003cb\u003e6\u003c/b\u003e(1): p. 31.\u003c/li\u003e\n\u003cli\u003eKroenke, K., R.L. 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Williams, \u003cem\u003eThe PHQ-9: validity of a brief depression severity measure.\u003c/em\u003e 2001. \u003cb\u003e16\u003c/b\u003e(9): p. 606–613.\u003c/li\u003e\n\u003cli\u003eTiruneh, K.T., et al., \u003cem\u003eDirect and indirect factors associated with health-related quality of life among PLHIV on second-line antiretroviral therapy at Dessie and Woldia Comprehensive Specialized Hospitals in Ethiopia: application of structural equation modelling.\u003c/em\u003e 2025.\u003c/li\u003e\n\u003cli\u003e\u003cem\u003e\u0026lt;national_guidelines_for_comprehensive_hiv_prevention_care_and_treatment_-_february_2022_pocket_guide.pdf\u0026gt;.\u003c/em\u003e\u003c/li\u003e\n\u003cli\u003eZeng, C., \u003cem\u003eApplying Health Stigma Framework to Examine the Mechanisms Of HIV-Related Stigma on Clinical Outcomes\u003c/em\u003e. 2021, University of South Carolina.\u003c/li\u003e\n\u003cli\u003eWiginton, J.M., et al., \u003cem\u003eHIV-related stigma and discrimination in health care and health-related quality of life among people living with HIV in England and Wales: A latent class analysis.\u003c/em\u003e 2023. \u003cb\u003e8\u003c/b\u003e(4): p. 487.\u003c/li\u003e\n\u003cli\u003eRasoolinajad, M., et al., \u003cem\u003eRelationship among HIV-related stigma, mental health and quality of life for HIV-positive patients in Tehran.\u003c/em\u003e 2018. \u003cb\u003e22\u003c/b\u003e: p. 3773–3782.\u003c/li\u003e\n\u003cli\u003eScheurer, D., et al., \u003cem\u003eAssociation between different types of social support and medication adherence.\u003c/em\u003e 2012. \u003cb\u003e18\u003c/b\u003e(12): p. e461-7.\u003c/li\u003e\n\u003cli\u003eLi, X.-M., et al., \u003cem\u003eAn evaluation of impact of social support and care-giving on medication adherence of people living with HIV/AIDS: a nonrandomized community intervention study.\u003c/em\u003e 2018. \u003cb\u003e97\u003c/b\u003e(28): p. e11488.\u003c/li\u003e\n\u003cli\u003eThomas, P.A., H. Liu, and D.J.I.i.a. Umberson, \u003cem\u003eFamily relationships and well-being.\u003c/em\u003e 2017. \u003cb\u003e1\u003c/b\u003e(3): p. igx025.\u003c/li\u003e\n\u003cli\u003eAtukunda, E.C., et al., \u003cem\u003eUnderstanding patterns of social support and their relationship to an ART adherence intervention among adults in rural Southwestern Uganda.\u003c/em\u003e 2017. \u003cb\u003e21\u003c/b\u003e: p. 428–440.\u003c/li\u003e\n\u003cli\u003eFerahtia, A.J.N.p.s.w.q.a.i.s.-a.r.b.o.w.q.i., \u003cem\u003eSee discussions, stats, and author profiles for this publication.\u003c/em\u003e 2021.\u003c/li\u003e\n\u003cli\u003eMasa, R., et al., \u003cem\u003eThe association of perceived, internalized, and enacted HIV stigma with medication adherence, barriers to adherence, and mental health among young people living with HIV in Zambia.\u003c/em\u003e 2022. \u003cb\u003e7\u003c/b\u003e(4): p. 443.\u003c/li\u003e\n\u003cli\u003eGohain, Z. and M.A.L.J.P. Halliday, \u003cem\u003eInternalized HIV-stigma, mental health, coping and perceived social support among people living with HIV/AIDS in Aizawl District—a pilot study.\u003c/em\u003e 2014. \u003cb\u003e5\u003c/b\u003e(15): p. 1794.\u003c/li\u003e\n\u003cli\u003eZeng ChengBo, Z.C., et al., \u003cem\u003eA structural equation model of perceived and internalized stigma, depression, and suicidal status among people living with HIV/AIDS.\u003c/em\u003e 2018.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Structural Equation Modeling, Internalized Stigma, PLHIV, Second-Line ART","lastPublishedDoi":"10.21203/rs.3.rs-8907378/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8907378/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eStigma forces individuals to hide their HIV status, discourages medical visits, hinders medication adherence, and restricts access to social support. HIV stigma refers to the process in which people living with HIV are socially discredited and devalued due to their HIV status. Hence, the aim of this study was to determine internalized stigma and associated factors among PLHIV on second-line ART in northeast Ethiopia.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eA facility-based cross-sectional study was conducted from January 13 to April 13, 2025, involving 825 randomly selected PLHIV on second-line ART. Data were gathered through document review and face-to-face interviews and analyzed with STATA version 17. Depression, social support and internalized stigma were assessed using the PHQ-9, Oslo-3 scales and HIV stigma scale, respectively. Structural equation modeling was applied, with statistical significance set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and effect sizes reported with 95% confidence intervals.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eIn structural equation model, internalized stigma was significantly associated with depression [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = 0.19, (95% CI: 0.11\u0026ndash;0.26)] and perceived stigma [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = 0.92, (95% CI: 0.806\u0026ndash;1.042)], indicating that higher level of depression and perceived stigma were related to higher level of internalized stigma. Whereas, social support was inversely associated with internalized stigma [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\widehat{\\beta\\:}\\)\u003c/span\u003e\u003c/span\u003e = -0.80, (95% CI: -0.862 to -0.732)], suggesting that greater social support was linked to lower internalized stigma.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis finding suggests that perceived stigma and depression fully mediate the relationship between social support and internalized stigma among PLHIV on second-line ART. Moreover, perceived stigma and depression functioned as parallel mediators in the relationship between social support and internalized stigma while also having a direct positive effect on internalized stigma. Social support, perceived stigmas and depression were significance predictors of internalized stigma.\u003c/p\u003e","manuscriptTitle":"Structural Equation Modeling of Depression, Stigma, and Social Support among People Living with HIV on Second-Line ART in Northeast Ethiopia: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 20:56:24","doi":"10.21203/rs.3.rs-8907378/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-12T16:22:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"148270704438569692244156659024567403779","date":"2026-05-04T15:35:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"279910560749176186186260677150996684550","date":"2026-05-04T13:50:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"107884099824000549224851738352630352044","date":"2026-04-22T16:12:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T18:36:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-24T03:28:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-19T04:10:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-19T04:08:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-18T08:32:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"74601d3f-f610-4bc1-9dee-f2ea7bf20692","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-12T16:22:58+00:00","index":151,"fulltext":""},{"type":"reviewerAgreed","content":"148270704438569692244156659024567403779","date":"2026-05-04T15:35:45+00:00","index":142,"fulltext":""},{"type":"reviewerAgreed","content":"279910560749176186186260677150996684550","date":"2026-05-04T13:50:06+00:00","index":139,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":63618235,"name":"Health sciences/Diseases"},{"id":63618236,"name":"Health sciences/Health care"},{"id":63618237,"name":"Biological sciences/Psychology"},{"id":63618238,"name":"Social science/Psychology"}],"tags":[],"updatedAt":"2026-02-27T20:56:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 20:56:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8907378","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8907378","identity":"rs-8907378","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}