BACKGROUND HIV-HCV co-infection is common in Manipur because of the increase in number of intravenous drug users (IDUs) and being eastern border state of India. HIV-HCV patients die of liver complications in spite of highly active antiretroviral therapy (HAART). The aim of the present study is to compare the clinico-immunological response to highly active antiretroviral therapy in HIV and HIV-HCV co-infection in Manipur. MATERIALS AND METHODS The present study was conducted in 45 HIV mono-infected (Group-I) and 45 HIV-HCV co-infected (Group-II) patients who were on first line antiretroviral treatment (ART). RESULTS In the present study, the clinico-immunological (CD4) response to ART in both the groups was recorded. The commonest route of transmission is heterosexual (62.2% and 53.3%) activity followed by IDUs (31% and 37%). The trend of CD4 is almost coinciding at initial 188.86 +/- 104.27 Vs. 179.00 +/- 98.19 cells/mm(3) but mean CD4 for HIV group is higher at 6th month, at 12th month and at 18th month with 502.82 +/- 272.22 Vs. 412.47 +/- 229.48 cells/mm(3) after ART as compared to HIV-HCV group significantly P<0.05 (P= 0.032). Further, the CD4 response was better in HIV-HCV with treatment of both HIV and HCV than without HCV treatment. CONCLUSION The present study showed that the immunological response to ART to both HIV and HIV-HCV co-infection groups is good, but better in HIV group. Further, amongst the HIV-HCV co-infection the immunological response was better to those who had undergone HCV treatment. So routine screening for HCV in HIV infected patients and starting HCV treatment early will result in better quality of life.