OBJECTIVE: This cross-sectional study investigated the associations of neighborhood-level factors with immune activation, systemic inflammation, and leukocyte telomere length in 110 sexual minority men with human immunodeficiency virus. METHOD: From 2013 to 2017, sexual minority men with human immunodeficiency virus who used stimulants were recruited in San Francisco, California and provided blood samples to measure the markers of immune activation, systemic inflammation, and leukocyte telomere length. To measure neighborhood-level indices, the home address for each participant was geocoded and linked to data from the Centers for Disease Control and Prevention. Hierarchical linear modeling was employed to investigate the associations of neighborhood-level factors with systemic inflammation and leukocyte telomere length. RESULTS: After adjusting for age, stimulant use, self-reported income, level of education, and race and ethnicity, residing in neighborhoods with greater percentages of poverty (β = .33, p <
.001) and a higher proportion of racial/ethnic minority residents (β = .26, p <
.05) were independently associated with higher levels of interleukin-6. Additionally, residing in neighborhoods with higher percentage of uninsured individuals was independently associated with higher tumor necrosis factor-alpha (β = .24, p <
.05). Indices of neighborhood-level adversity were additionally associated with providing a urine sample that was reactive for stimulants (OR = 1.31, p = .002), which was, in turn, associated with shorter leukocyte telomere length (β = -.31, p <
.05). CONCLUSIONS: Future longitudinal research should examine the biobehavioral pathways linking neighborhood-level factors and stimulant use with systemic inflammation and cellular aging. (PsycInfo Database Record (c) 2025 APA, all rights reserved).