Mental Health in Persons with HIV: Challenges and Opportunities

Despite effective antiretroviral therapy (ART), some persons with HIV (PWH) continue to experience persistent neurocognitive and mental health challenges. Mental disorders are among the most common comorbidities, with depression being the most prevalent. These conditions are often overlooked in routine HIV care, and may contribute to cognitive impairment, drive greater healthcare utilization, and reflect broader health inequities. This thesis examines the interplay between mental health and HIV-health, drawing on systematic review, cohort analysis, health administrative data across four studies. The thesis begins with a systematic review and meta-analysis of 44 studies assessing the role of depressive symptoms (DS) in episodic memory in PWH. Results showed that immediate recall, but not delayed recall, was significantly lower in PWH with DS, with a pooled Hedges' g of -0.390 (95% CI: -0.683 to -0.097). Approximately 27% of studies reported a significant inverse correlation between DS severity and memory scores, with longitudinal data indicating that memory decline was most evident among individuals with moderate-to-severe DS. These findings highlight DS as a critical determinant of memory dysfunction and a target for cognitive health preservation in HIV care. Building on this evidence of the literature review, the second study analyzed original data from 354 PWH enrolled in a prospective Canadian cohort, including 102 with DS and 252 without. Verbal memory performance measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) was significantly lower in the DS+ group compared to the DS- group in immediate memory but not delayed memory, despite both groups falling within normative ranges. Longitudinal follow-up (N = 52) revealed that individuals with DS experienced a greater delayed memory decline over time, but not immediate memory. Memory was associated with quality of life, education, and mental health status, but not with HIV biomarkers or ART regimen. These results suggest that depressive symptoms, rather than HIV-related disease factors, are more influential in shaping cognitive outcomes in treated PWH. The third study broadened the focus to the health system by utilizing a validated case definition and linking administrative health datasets from Alberta to examine hospital and emergency department (ED) utilization over three years in 3,445 PWH, of whom 933 had documented mental health and/or substance use disorders (MHS+). MHS+ individuals had significantly higher rates of ED or hospital use (78% vs. 48%; p < 0.001) and incurred greater average hospitalization costs ($58,190 ± 98,361 vs. $35,031 ± 64,203; p < 0.01). ED visits among MHS+ were disproportionately related to mental health crises (28% vs. 4%), physical trauma (45% vs. 19%), and ambulatory-care-sensitive conditions (30% vs. 14%). These findings emphasize the need for integrated and preventative care models to reduce avoidable healthcare utilization and economic burden in PWH with comorbidities. Finally, the fourth study extended the analysis into the social domain by focusing on gender as modifiable factor in HIV health. For this study, we developed and validated a gender diagnostic index with potential health-relevance using six indicators (e.g., caregiving, occupation type, household responsibility) in a cohort of 201 PWH from the same Canadian cohort as study 2 (164 men, 37 women; 134 identifying as sexual and gender minorities [SGM]). The gender metric was derived from a large representative cohort of Canadians (N=2,227). Regardless of biological sex, in the HIV cohort, a more “feminine” gender index was associated with elevated risk of depressive symptoms, psychiatric comorbidities, ART side effects, and poorer cognitive performance. The majority (73% of the cohort) had at least one adverse health outcome. These associations were most pronounced in SGM, indicating structural and psychosocial vulnerabilities tied to gender that extend beyond sex assigned at birth. This dissertation demonstrates that the health of people with HIV must be understood within a broader psychosocial, healthcare, and social context than through biological or virologic markers alone. The findings show how mental health, substance use, cognitive symptoms, healthcare access, and gender roles intersect to shape lived experiences and outcomes among PWH. Rather than focusing on any single determinant, this dissertation argues for a shift toward integrated, person-centered models that capture the complexity of HIV. Future research should build on this evidence to develop interventions that are aware and responsive to both clinical needs and structural inequities to better support wellness and equity for PWH.

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