In limited resource countries, the effectiveness of first-line antiretroviral treatment in HIV-positive patients could be measured by its strong predictor, the CD4 count for the initiation of antiretroviral therapy and proper management of disease progress. Even though, in addition to HIV, there are many factors which can influence the CD4 cell count considered to be constant. Methods : A retrospective cohort study was conducted to examine the response of first-line antiretroviral treatment on CD4 count in HIV-positive patients at 0, 6, 12 and 24 months, who enrolled in the first month of 2013 and followed up to begining-2018.The covariance components model was employed to determine the CD4 count changes over time. Results : A total of 320 ART attendants were used to analyze their data. The majority 294(92.4%) of the respondents were started AZT based ART regimens, but there was no a significance difference among ART regimens for CD4 cell count. The mean baseline of CD4 cell count (166 cells/ mm 3 ) was positive associated (p<0.001) with CD4 count increment at time of follow ups and was increased to 274 cells/mm 3 significantly (p<0.001) at six months of initiation of ART. Working functional status and younger age, also contribute for CD4 count significant change. Conclusion : The change in CD4 count was high at the first 6 month than 12 and 24 month. All ART regimens without significance difference that increased mean CD4 count at the study period. Hence, it can be concluded that ART is effective enough in improving the immune system and slowing the progression of HIV infection to AIDS. Keywords : CD4 count, ART, Boru meda hospital