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Longitudinal association between internalized HIV stigma and antiretroviral therapy adherence for women living with HIV

the mediating role of depression

Turan, Bulent; Rice, Whitney S.; Crockett, Kaylee B.; Johnson, Mallory; Neilands, Torsten B.; Ross, Shericia N.; Kempf, Mirjam-Colette; Konkle-Parker, Deborah; Wingood, Gina; Tien, Phyllis C.; Cohen, Mardge; Wilson, Tracey E.; Logie, Carmen H.; Sosanya, Oluwakemi; Plankey, Michael; Golub, Elizabeth; Adimora, Adaora A.; Parish, Carrigan; Weiser, Sheri D.; Turan, Janet M.

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doi: 10.1097/QAD.0000000000002071
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Abstract

Introduction

Despite effective treatments for HIV, treatment adherence and viral suppression remain suboptimal among many people living with HIV (PLWH), especially for certain subgroups, including Black and Latina women [1,2]. Identifying and addressing psychosocial barriers to antiretroviral therapy (ART) adherence – such as internalized stigma, when PLWH endorse and accept negative attitudes about PLWH [3] – are vital to enhancing rates of ART adherence and viral suppression.

A large body of research – mainly composed of cross-sectional and qualitative studies – suggests that HIV-related stigma is associated with suboptimal adherence to medication and HIV clinic visits [4–8], including studies of women living with HIV in the United States [9]. Both conceptual frameworks and empirical work suggest internalized HIV stigma has a stronger relationship with ART adherence than other dimensions of HIV-related stigma (anticipated, perceived community, and enacted) [3,10]. Furthermore, cross-sectional research suggests that, for women, the association between internalized stigma and ART adherence is mediated by depression symptoms [11].

A comprehensive systematic review of stigma and ART adherence identified only seven longitudinal studies in the global literature and six of these reported null findings on the relationship between HIV-related stigma and treatment adherence [4]. One of these longitudinal studies found that individuals who reported higher levels of HIV-related stigma were more likely to self-report missed medications [12]. In another article presenting meta-analyses of HIV-related stigma and health outcomes, nine additional longitudinal studies were identified (out of 120 included studies), but none focused on ART adherence as an outcome [5]. A recent review by Sweeney et al.[7], focusing specifically on HIV-related stigma and ART adherence, identified only five additional longitudinal studies (out of 38 in the review), two in the United States and three in Africa or Asia. The two longitudinal studies conducted in the United States did not find significant associations of stigma with nonadherence [7].

Relatively few studies have a specific focus on internalized HIV-related stigma, and several use lack of disclosure as a proxy for stigma, instead of measuring stigma explicitly. Furthermore, prior studies in this area have been conducted with predominantly male and white samples [7,13], with a few notable exceptions [14,15]. Thus, additional longitudinal research is needed on the effects of internalized HIV-related stigma on ART adherence as well as on mediating mechanisms, especially in women and in racial/ethnic minority populations, who are disproportionately affected by HIV.

The purpose of the present longitudinal study was to investigate whether internalized HIV-related stigma predicts suboptimal ART adherence in women living with HIV. Because studies have supported links among internalized HIV-related stigma, depression symptoms, and ART adherence [11,16], we also examined the hypothesis that depression symptoms mediate the effect of internalized HIV stigma on ART adherence. To design effective supportive interventions, it is necessary to understand the causal mechanisms linking internalized stigma with suboptimal ART adherence over time.

Methods

Participants and procedures

Data were collected from women living with HIV participating in the Women's Interagency HIV Study (WIHS) [17,18]. WIHS is a multisite prospective study investigating HIV disease progression, comorbidities, and the behavioral impact of HIV infection among women in the United States. Since 1994, data have been collected from participants in six US sites (Bronx, Brooklyn, Washington DC, Chicago, Los Angeles, and San Francisco) every 6 months via interviews, physical assessments, and laboratory tests. To further enhance the representativeness of the cohort, new participants were enrolled between 2013 and 2015 at sites in the US South; including Atlanta, Birmingham, Jackson, Miami, and Chapel Hill. The median age of WIHS participants is 50 years. Around 75% of HIV-positive WIHS participants identify as African-American, 14% as white, and 14% as Hispanic. All participants provided written informed consent, with study activities being approved by each site's Institutional Review Board.

A measure of internalized HIV-related stigma was added to the battery of WIHS measures in 2013. For current analyses, participants’ first assessment of internalized HIV-related stigma and assessments of other variables at that time were used as baseline measures (Time one or T1, visit occurring in 2013/14). The follow-up date was approximately 2 years later (T3, 2015/16). For most participants, a measure of depression symptoms assessed at approximately 18 months after the baseline (T2, 2014/15) was available and used in mediation analyses. A total of 914 HIV-positive WIHS participants were on ART at baseline and had complete data on these variables at T1 and T3 (as well as relevant covariates) for the longitudinal analyses, and 862 had complete data for the mediation analyses (T1, T2, and T3; refer to footnotes to Table 1 and Fig. 1).

Table 1
Table 1:
Sample characteristics, correlations, and adjusted relationships of Time 1 (T1) predictors with antiretroviral therapy adherence at Time 3a.
Fig. 1
Fig. 1:
Depression symptoms at T2a mediate the effect of internalized HIV-related stigma at T1 on antiretroviral therapy adherence at T3 (n = 862).Note: Associations are presented as path coefficients (unstandardized). Depression symptoms and antiretroviral therapy adherence at T1 (as well as the covariates race, age, time on antiretroviral therapy, illicit drug use, income, education, and region) were also entered as control variables. aFifty-two participants did not have data on depression symptoms at T2 or T1. These 52 participants did not differ from the participants included in the mediation analysis, on internalized stigma or any of the covariates (all P values more than 0.10), and list-wise deletion was used. bWhen depression at T2 is in the model. * P less than 0.05; ** P less than 0.01.

Measures

Adherence

Participants self-reported how often they took their ART as prescribed over the past 6 months. Response options were ‘100% of the time’, ‘95–99% of the time’, ‘75–94% of the time’, ‘less than 75% of the time’, and ‘I haven’t taken any of my prescribed medications’. Previous research provides support for the validity of this measure of adherence [19,20]. As in previous studies, we dichotomized the measure at 95% or higher versus lower than 95% [20,21].

Internalized HIV-related stigma

This was assessed with the negative self-image subscale of the revised HIV Stigma Scale (range 1–4), which consists of seven items (e.g., ‘I feel I’m not as good as others because I have HIV.’), rated on a four-point scale (strongly disagree to strongly agree) [22,23]. Cronbach's alpha was 0.86 in the current sample.

Depression symptoms

The 20-item Center for Epidemiological Studies Depression (CES-D) Scale [24] is used to assess depression symptoms in the WIHS. In previous studies, depression symptoms, as measured by CES-D, have been shown to predict ART adherence [25,26].

Analytical methods

Logistic regression analysis was conducted to examine the association between internalized HIV stigma at T1 and ART adherence at T3. The following variables (measured at T1), which have been found important when examining ART adherence in previous research [27–30], were included as covariates: ethno-racial identity, age, time on ART, illicit drug use, income, education, and US region (south versus other locations). Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) controlling for these covariates are reported. Next, ART adherence at T1 was also added to the model as a control variable. Finally, mediation analysis using bootstrapping (with the program PROCESS, a macro used with SPSS, version 24 (IBM Corp., Armonk, NY, USA) [31]) was conducted to test whether the association between internalized stigma at T1 and ART adherence at T3 is mediated by depression symptoms at T2. This analysis controlled for depression symptoms and ART adherence at T1 (as well as the covariates). A significant indirect effect indicates mediation.

Results

Sample characteristics and associations of covariates with stigma and depression symptoms at T3 are presented in Table 1. Suboptimal adherence at T3 was reported by 14.1% of the sample. As can be seen in Table 1, higher internalized HIV-related stigma at T1 predicted lower odds of optimal ART adherence at T3 (AOR = 0.61, P = 0.001, 95% CI [0.45, 0.82]). When ART adherence at T1 was added as a control variable, internalized HIV-related stigma at T1 again predicted lower odds of optimal ART adherence at T3 (AOR = 0.64, P = 0.005, 95% CI [0.47, 0.87]).

Mediation analysis (Fig. 1) revealed a significant indirect effect of internalized HIV stigma at T1 on suboptimal ART adherence at T3 through depression symptoms at T2 (while controlling for depression symptoms and ART adherence at T1; B = −0.05, SE = 0.03, 95% CI [−0.11, −0.006]).

Discussion

These results in a large sample of women living with HIV in multiple locations across the United States provide strong longitudinal support for the hypothesis that internalized HIV-related stigma results in suboptimal ART adherence. Contrary to some prior longitudinal studies, we found a significant relationship between HIV-related stigma and ART adherence. Our focus on internalized HIV-related stigma was likely a key reason, as internalized stigma tends to have a stronger relationship with ART adherence behaviors than other dimensions of HIV-related stigma, both theoretically and empirically [3,10,32]. Furthermore, we found that depression symptoms mediate the effect of internalized HIV stigma on suboptimal ART adherence (again using longitudinal analyses to preserve the temporal sequence among the independent variable, mediator, and outcome variable), providing evidence for the contention that internalized HIV-related stigma affects adherence through depression.

These results add to the evidence from cross-sectional analyses of data from women living with HIV in the United States [32] and Canada (which found that depression mediates the pathways from negative self-image to current ART use and ART adherence [15]). These relationships are likely to be relevant for other populations as well. Among gay and bisexual men living with HIV, recent results from an experience sampling method study (in which participants report on their experiences in real-time on repeated occasions) revealed that experiences of internalized HIV-related stigma were concurrently associated with depressed and anxious affect, anger, and emotion dysregulation [33].

Our results have important implications for interventions to improve ART adherence and HIV-related health for women living with HIV. Addressing HIV-related stigma early in the diagnosis and treatment initiation process may be a key to reducing risk for depressive symptoms and suboptimal adherence [3]. Acceptance-based approaches may be effective for reducing internalized HIV-related stigma [34], and can be tailored for brief interventions in HIV care settings. Elucidation of depression as an important intervening mechanism can also provide targets for interventions and supportive services. Depression interventions, such as cognitive behavior therapy, have yielded promising results in improving ART adherence [35–37]. Thus, future intervention studies should examine long-term effectiveness of programs specifically tailored for women living with HIV, which address depression and internalized stigma simultaneously.

The current study has limitations. The WIHS is a sample of older women participating in an interval cohort study at urban research centers, and may not be representative of the general population of women living with HIV in the United States. The WIHS southern sites were not fully enrolled at T1 for the current study, so fewer of their participants could be included in these analyses. In addition, the outcome measure of ART adherence is based on self-report and may be subject to recall and social desirability biases. However, brief self-report measures of ART adherence have been found to be robust and reliable [38]. In addition, ART adherence and other health behaviors are likely to be influenced by other psychosocial factors (such as self-efficacy, attachment styles, and intersectional and structural stigma and discrimination) [39–42], which are not measured in the national WIHS data collection and therefore are not captured in the current analyses. Future research and programs can extend this work to examine clinical outcomes and utilize these findings to develop, investigate, and evaluate interventions to reduce stigma, address depression, and improve the mental and physical health of women living with HIV.

Acknowledgements

We wish to acknowledge the assistance of the WIHS program staff and the contributions of the participants who enrolled in this study. This study was funded by Women's Interagency HIV Study (WIHS) substudy grants from the National Institute of Mental Health, R01MH104114 and R01MH095683. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (M.-C.K. and D.K.-P.), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and G.W.), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (M.C. and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (A.A.A.), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and P.C.T.), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and E.G.), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I–WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA), and P30-AI-050410 (UNC CFAR). This research was also supported by the University of Alabama at Birmingham (UAB) Center for AIDS Research CFAR, an NIH funded program (P30 AI027767) that was made possible by the following institutes: NIAID, NCI, NICHD, NHLBI, NIDA, NIA, NIDDK, NIGMS, and OAR. Trainee support was provided by the Agency for Healthcare Research and Quality (grant number T32HS013852).

Conflicts of interest

There are no conflicts of interest.

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Keywords:

adherence; depression; internalized; stigma; women

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