The Long-Term Impact of Symptom Burden on Health-Related Quality of Life among Adults with HIV in the United States

BACKGROUND: Due to antiretroviral therapy, people with HIV (PWH) are living longer than ever before. This shift in health outcomes has led to increased prioritization of health-related quality of life (HRQOL), which has been linked to several positive outcomes, including survival. Although evidence suggests that symptom burden influences HRQOL, most research has been cross-sectional, conducted outside the U.S., or based on earlier treatments. Moreover, limited research has examined the mechanisms through which symptom burden influences HRQOL, which is critical to informing interventions to improve wellbeing. The purpose of this dissertation is to address these gaps by assessing the longitudinal relationships among symptom burden, depressive symptoms, physical activity, and HRQOL among PWH receiving care in the modern treatment era. METHODS: This study used data from a large, geographically diverse clinical cohort in the U.S. For aim 1 (n=6,113), I used multivariable linear regression to assess the longitudinal association between symptom burden and HRQOL, adjusting for demographic and clinical characteristics as well as baseline HRQOL, depressive symptoms, and physical activity. A supplemental analysis examined associations between symptom clusters and HRQOL. For aim 2 (n=4,169), I conducted longitudinal mediation analyses to test whether depressive symptoms and physical activity independently mediated the relationship between symptom burden and HRQOL. RESULTS: Findings from the first study suggest that higher symptom burden at baseline was associated with lower HRQOL at follow-up (b = -0.02, p<.0001). Furthermore, all symptom clusters (gastrointestinal, psychological, pain, and body image) predicted lower HRQOL; however, pain-related symptoms had the strongest effect (β = -0.02, p<.0001), compared to other clusters. Longitudinal mediation analyses indicated that depressive symptoms significantly mediated the relationship between symptom burden and HRQOL, but physical activity did not. However, baseline physical activity independently predicted HRQOL at follow-up. DISCUSSION: This dissertation study advances understanding of HRQOL among PWH in the modern treatment era by demonstrating that symptom burden—particularly pain-related symptoms—negatively influences HRQOL over time and that depressive symptoms play a key mediating role in this relationship. The findings highlight the importance of integrating symptom management and mental health support in interventions designed to enhance HRQOL among PWH in the U.S.