Medication literacy and treatment adherence in people living with human immunodeficiency virus: Mediating effects of psychosocial factors

Table 1 Distinct mediating pathways of stigma and their impact on treatment adherence

Mediating pathway	Mechanism of action	Impact on outcomes	Group differences	Ref.
External stigma → medication literacy → adherence	Social exclusion restructures access to health information through institutional discrimination	Patients avoid reading medication inserts, leading to reduced accuracy in understanding drug interactions; an "information desert" emerges	Cultural specificity exacerbates information-processing difficulties; women may face more barriers in accessing health information	[18-20]
Internalized stigma → self-efficacy → adherence	Self-stigmatization undermines treatment confidence via cognitive fusion	Patients pathologically associate HIV status with self-worth, showing a "self-punishment" tendency in treatment decisions	Internalized stigma is positively correlated with psychological inflexibility, associated with reduced gray matter density in the anterior insula	[23,24]
Moderating effects of stigma	Multiple discrimination experiences in racial and sexual minority groups	African American patients exhibit greater distrust toward prescribing intentions; sexual minorities experience unique spatiotemporal stigma burdens	African Americans face dual discrimination (race + HIV status); men who have sex with men report higher internalized stigma in family contexts; transgender women experience a triple-layered stigma effect	[21,27]
Concealment of treatment behavior	Patients adopt systematic concealment strategies to reduce identity exposure risk	Strategies such as altering appointment times or modifying medical records increase complexity and risk in health management	Women are more likely to use "medication repackaging" due to family role conflicts; men who have sex with men build anonymous support systems through virtual networks	[62-65]

HIV: Human immunodeficiency virus.

Table 2 Key psychosocial mediating variables influencing treatment adherence in people living with human immunodeficiency virus

Mediating variable	Definition	Mediating mechanism	Key findings	Ref.
Stigma	Social stigma and self-stigmatization related to HIV	Affects access to health information and self-efficacy through external and internal stigma pathways	Stigma leads to avoidance of medication information and increased risk of dosage errors; internalized stigma is significantly associated with psychological inflexibility	[21,22]
Self-efficacy	Patients’ belief in their ability to successfully perform treatment behaviors	Promotes translation of health knowledge into treatment behaviors via the self-regulatory system in social cognitive theory	Higher self-efficacy is significantly associated with better adherence; treatment success reinforces efficacy, forming a positive feedback loop	[31,32]
Social support	Support from peers, family, and healthcare providers	Provides emotional and informational support, buffers stigma, and enhances self-efficacy	Peer support is strongly linked to long-term retention, adherence, and viral suppression; family support buffers the negative impact of low medication literacy on adherence	[52,53]
Depression/anxiety	Mental health problems associated with HIV	Alters cognitive processing through functional decoupling of the prefrontal–limbic system	Depression reduces glucose metabolism in the prefrontal cortex, impairing working memory and executive function; anxiety heightens amygdala–insula reactivity, leading to cognitive overload	[58-61]
Patient–provider trust	Degree of trust patients have in healthcare providers	Enhances the therapeutic alliance and reduces suspicion and fear of the medical system	Lower levels of trust are linked to poorer adherence and outcomes; especially relevant among minority populations	[89]

HIV: Human immunodeficiency virus.

Table 3 Mechanisms through which self-efficacy mediates the relationship between medication literacy and treatment adherence

Pathway of action	Neural mechanism	Psychological and behavioral manifestations	Influencing factors	Ref.
Medication literacy → self-efficacy → adherence	Functional coupling between the prefrontal cortex and striatum enhances executive control network efficiency	Patients accurately interpret medication instructions and anticipate side effects, strengthening their sense of agency in disease management	Culturally adapted health education integrates traditional medical beliefs with modern biomedical knowledge, enhancing confidence in medication use	[33-35]
Treatment success → reinforced self-efficacy → literacy improvement	Activation of D2 receptors in the striatum enhances neural markers of positive behavioral reinforcement	Patients consistently achieve micro-level treatment goals, forming a feedback loop of "successful experience → efficacy gain → knowledge deepening"	Peer support networks reshape patients’ self-narratives in virtual spaces; trust in healthcare providers modulates dopaminergic projections from the ventral tegmental area to the prefrontal cortex	[43-47]
Psychodynamic system of behavioral reinforcement	Positive feedback in the dopaminergic reward system drives the acquisition and maintenance of treatment-adherent behavior	High-efficacy patients exhibit a 40% increase in behavioral reinforcement learning rate, especially in managing side effects	Urban living environments offer real-time medical feedback channels; economic empowerment frees cognitive resources for health management	[59,72]
Dynamic evolution of self-efficacy	Stage-based construction of efficacy across theoretical models	In the initiation phase, trust in healthcare providers plays a central role; in the maintenance phase, the influence of peer support networks increases	Digital interventions using virtual reality simulate medication-taking scenarios, overcoming spatial and temporal limitations of traditional interventions	[61]

Table 4 Mechanisms through which social support networks influence treatment adherence in people living with human immunodeficiency virus

Type of support	Mechanism of action	Key research findings	Implications for intervention	Ref.
Peer support	Buffers HIV-related stigma through emotional and informational support	Strongly associated with long-term retention, adherence, and viral suppression among people living with HIV; reduces internalized stigma	Develop peer-based support networks, especially virtual support communities	[47,50,51]
Family support	Serves as a buffering variable between literacy and adherence, providing emotional and practical aid	Mitigates the negative effects of low medication literacy on adherence; improves adherence through medication reminders and accompaniment to care	Involve family members in medication supervision, especially for children and adolescents	[53]
Patient–provider trust	Promotes adherence by reducing patients’ suspicion and fear toward the healthcare system	Lower trust is linked to poorer adherence and treatment outcomes; particularly affects racial and ethnic minority groups	Enhance provider communication skills and adopt culturally adaptive strategies	[56]
Community support networks	Mitigate the negative effects of spatial exclusion by creating alternative healthcare pathways	Community health workers play a key role in sustaining access to antiretroviral therapy; stigma at the community level shapes care-seeking geography	Implement task-sharing interventions with lay providers; build destigmatized support networks	[87]

HIV: Human immunodeficiency virus.

Table 5 Research limitations and future directions

Limitation	Specific issues	Future research directions	Suggestions for innovative methods	Ref.
Lack of longitudinal data	Existing studies predominantly adopt cross-sectional designs, limiting the ability to capture dynamic relationships between psychosocial factors and treatment adherence	Establish longitudinal cohorts integrating biomarkers with behavioral monitoring	Use mobile health technologies for real-time data collection; adopt mixed-method approaches to capture dynamic fluctuations of mediating variables	[100,101]
Methodological constraints in quantifying mediation effects	The complexity of multiple mediation models challenges traditional statistical methods; failure to account for intergroup heterogeneity may bias effect estimates	Develop hybrid models integrating computational psychiatry and structural equation modeling	Use bias-corrected bootstrap methods to relax normality assumptions in mediation testing; apply Bayesian approaches to improve the accuracy of multilevel mediation models	[102-106]
Blind spots in evaluating long-term effects of digital interventions	Current digital health studies mainly focus on short-term adherence improvements, lacking exploration of behavior maintenance mechanisms	Construct a "digital intervention life-cycle" evaluation framework	Leverage blockchain technology for decentralized data tracking; include neuroplasticity markers as biomarkers of long-term intervention efficacy	[107-108]
Insufficient comparative research on cross-cultural interventions	Lack of systematic comparisons of intervention effectiveness across different cultural contexts	Develop a three-dimensional evaluation framework for cross-cultural intervention outcomes	Compare prefrontal–limbic system responses to intervention stimuli across cultural groups; analyze the impact of geographic patterns of community-level stigma on delivery efficiency; evaluate the transferability of cultural archetypes in virtual health communities	—