Antiretroviral therapy that is given to HIV / AIDS patients is a combination therapy. The treatment given for HIV/AIDS patients are combination of three or more drugs that called HAART (high active antiretroviral therapy). The first line therapy recommended by WHO (2010) is zidovudine combination and tenofovir combination. Both the combination is effective to restore the patient's immune system that is characterized by an increase in the number of CD4 + cells. The aim of this study was to compare the effectiveness therapy of zidovudine combination to tenofovir combination based on the value of CD4⁺ cell count. 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 zidovudine combination group and 53 patients for tenofovir combination group. Wilcoxon Signed Rank test results show both combination therapy is effective in increasing the CD4 + cells (p = 0,000). The conclusion is that zidovudine combination and tenofovir combination is equally effective as measured by an increase in the number of CD4+ cells count. Factors affecting the increase is the number of CD4+ cell count at baseline. CD4+ baseline ≤ 200 cells / mm3 l5 times more effective in increasing the number of CD4+ cell count compared to the number of CD4+ baseline > 200 cells / mm3.