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OBJECTIVES: The purpose of this study was to determine the effect of release from prison and subsequent re-incarceration on the viral loads of HIV-infected individuals receiving highly active antiretroviral therapy (HAART). METHODS: Fifteen re-incarcerated HIV-infected prisoners on HAART were identified from a retrospective cohort of HIV-infected prison inmates released from January 1, 1997, to August 31, 1999. The re-incarcerated prisoners were matched (1:2) to 30 HIV-infected incarcerated prisoners on HAART who remained incarcerated during the re-incarcerated participants' release time period. The outcomes measured were plasma HIV RNA levels, CD4+ lymphocyte counts, percentage of re-incarcerated and incarcerated participants with plasma HIV RNA levels <400 copies/mL, and the median change in plasma HIV RNA levels of the re-incarcerated and incarcerated participants at the end of the study. RESULTS: At the beginning of the study, 8/15 re-incarcerated participants had plasma HIV RNA levels <400 copies/mL, compared with 15/30 incarcerated participants. At the end of the study, only three of those eight re-incarcerated participants had plasma HIV RNA levels <400 copies/mL, compared with 14/15 incarcerated participants (p=0.0086). The median change in plasma HIV RNA levels of the re-incarcerated participants was 1.29 log10 copies/mL (interquartile range 0.04 to 1.70), compared with -0.03 log10 copies/mL (interquartile range -0.65 to 0.09) in the incarcerated participants (p=0.0183). CONCLUSIONS: Release from prison was associated with a deleterious effect on virological and immunological outcomes. These data suggest that comprehensive discharge planning efforts are required to make certain that HIV-infected inmates receive access to quality care following incarceration.