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We used data from the Veterans Aging Cohort Study (VACS) to explore the relationship between incarceration and HIV disease outcomes and evaluate potential mediators of this relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HIV disease outcomes included: low CD4 counts (&lt;200 cells\/mL), detectable viral RNA loads (&gt;500 copies\/mL), and the VACS Index score. We performed a mediation analysis among 1,591 HIV\u2010infected patients to examine whether unhealthy alcohol use, drug use, primary care engagement, or antiretroviral adherence mediated observed associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 1,591 HIV\u2010infected patients, 47% reported having a history of incarceration. In multivariate analyses, a history of incarceration was associated with a higher VACS Index score (\u03b2 2.47, 95% CI 0.52\u20134.43). Mediation analysis revealed that recent drug use attenuated the association by 22% (\u03b2 1.93, 95% CI \u22120.06, 3.91) while other proposed mediators did not.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Scientific Significance<\/jats:title><jats:p>Improving access to drug treatment when incarcerated and upon release may be an important target to improving the health of HIV\u2010infected individuals with a history of incarceration. 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