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Identify the determinants and consequences of interrupting and discontinuing highly active antiretroviral therapy (HAART) among a population-based cohort of HIV-infected men.Longitudinal analyses were applied to 2916 person-visit pairs (589 men) of continuous HAART use, 243 person-visit pairs (154 men) during which HAART was interrupted, and 151 person-visit pairs (130 men) in which HAART was discontinued by the second visit. HIV RNA increase was defined as ≥1 log10 copies/mL across the visit pairs.Younger age, black race, geographic location, higher HIV RNA level, depression, shorter time on HAART, lower medication adherence, and not taking a lamivudine-containing regimen predicted interrupting HAART use. Younger age, higher HIV RNA level, depression, and taking an abacavir- or lopinavir-containing regimen predicted discontinuing HAART. Among men with ≤1000 HIV RNA copies/mL, approximately 5% of those who interrupted HAART for ≤7 days and those who continued HAART had an HIV RNA increase. Men with longer interruptions and HAART discontinuers had significantly higher rates of HIV RNA increases (35.7% and 70.5%, respectively). Discontinuation and long interruptions resulted in lower CD4 cell counts.Host characteristics play a role in short interruptions, whereas longer interruptions may be clinically indicated. These longer stoppages had further virologic and immunologic consequences, however.