Antiretroviral therapy that is given to HIV / AIDS patients is a combination therapy. Given first-line therapy is a combination of zidovudine and Tenofovir. Both the combination is effective to restore the patient's immune system that is characterized by an increase in the number of CD4 + cells. But giving the combination also cause side effects in patients. The aim of this study was to compare the combination of zidovudine and  combination of Tenofovir to the  effectiveness of therapy and incidence of side effects. The study was conducted in March-June 2016 at Poli Teratai and medical records unit of RSAL Mintohardjo. The data collected is a medical record. The study design used is cross sectional comparative with a sample size of 75 patients for the combination of zidovudine group and 53 patients to the combination of tenofovir group. Wilcoxon Signed Rank test results show both combination therapy is effective in increasing the CD4 + cells. Chi-Square test results show that both combinations affect a declining in hemoglobin. Then the results of logistic regression test show that CD4 + count baseline ≤ 200 cells / mm 3 had a 4.55 times greater influence to increase the number of CD4 + cells when compared with  CD4 + count baseline > 200 cells / mm3 and the combination of zidovudine had a 4.59 times greater risk for impaired hemoglobin compared to the combination of tenofovir.