Little is known about the impact of acute hepatitis C virus (HCV) co-infection on HIV-1 disease progression. We investigated CD4 cell count and HIV RNA concentration changes after HCV infection in individuals chronically infected with HIV-1.We selected individuals that had the last negative and first positive HCV RNA test less than 1 year apart. Bivariate linear mixed-effects regression was used to model trends in HIV RNA level and CD4 cell count from 2 years before the last negative HCV RNA test until the first of the following dates: start of anti-HCV medication, change in combination antiretroviral therapy (cART) status, and end of follow-up.At the estimated time of HCV co-infection, of 89 individuals, 63 (71%) were cART-treated and 26 (29%) were not on cART. In persons on cART, median CD4 cell count declined from 587 to 508 cells per cubic millimeter (P <0.0001) during the first 5 months after HCV infection and returned to 587 cells per cubic millimeter after 2.2 years. Also, the probability of an HIV RNA >50 copies per milliliter peaked to 18.6% at HCV co-infection, with lower probabilities 6 months before (3.5%, P = 0.006 compared with peak probability) and after (2.9%, P = 0.009). In persons not on cART, no significant impact of HCV co-infection on trends in the HIV RNA level or CD4 cell count was observed.Acute HCV infection in cART-treated, chronically HIV-infected patients was associated with a temporary decrease in CD4 cell counts and increased risk of HIV viremia >50 copies per milliliter. This may increase the risk of further HIV transmission.