People living with HIV (PLWH) experience a higher prevalence of depression (31%) and anxiety (15–40%) than the general population. Although antiretroviral therapy (ART) has transformed HIV into a manageable chronic condition, its impact on mental health remains complex and may vary by adherence, regimen characteristics, and socioeconomic context. This narrative re view synthesizes evidence from six geographically and socioeconomically diverse cohorts (comprising over 300,000 individuals across the United States, China, Japan, Kazakhstan, Rwanda, and Tanzania) to evaluate the relationship between ART param eters and psychiatric outcomes. A search of PubMed/MEDLINE and Google Scholar identified observational and prospective studies published between 2012 and 2024. Synthesized findings reveal consistent associations between mental health and ART engagement, though non-causal in design. In LMICs and youth cohorts (e.g., Rwanda, 37% suboptimal adherence; Tanzania, n = 407) depressive symptoms, anxiety, and elevated systemic inflammatory markers (CRP, sTNFR-II) correlated with lower adherence. Conversely, US population-level data indicated lower odds of mood disorders among ART recipients compared to untreated individuals, while Japanese prospective data demonstrated improved sleep and quality-of-life scores following regi men simplification to single-tablet regimens. Evidence suggests that the psychological benefits of ART depend heavily on adher ence thresholds (≥90%) and regimen tolerability rather than treatment initiation alone. Potential underlying pathways include viral suppression and reduced neuroinflammation, alongside psychosocial gains such as enhanced self-efficacy and healthcare engagement. Given the observational nature of most data, ART should be viewed as a contributing factor rather than a direct cure for psychiatric burden. Integrating routine mental health screening into HIV care may optimize both virological adherence and psychological well-being globally.