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To assess the relation between alcohol consumption and laboratory markers of HIV disease progression.We prospectively assessed CD4 cell counts, HIV RNA levels, and alcohol consumption for up to 7 years in 595 HIV-infected persons with alcohol problems recruited between 1997 and 2003. We investigated the relation of these markers of HIV disease progression to alcohol consumption using longitudinal regression models controlling for known prognostic factors, including adherence and depressive symptoms, and stratified by antiretroviral therapy (ART) use.Among subjects who were not on ART, heavy alcohol consumption was associated with a lower CD4 cell count (adjusted mean decrease of 48.6 cells/μL compared with abstinence; P = 0.03) but not with higher log10 HIV RNA. Among subjects who were on ART, heavy alcohol consumption was not associated with a lower CD4 cell count or higher log10 HIV RNA.Heavy alcohol consumption has a negative impact on the CD4 cell count in HIV-infected persons not receiving ART. In addition to the known deleterious effects of alcohol on ART adherence, these findings suggest that avoiding heavy alcohol consumption in patients not on ART may have a beneficial effect on HIV disease progression.