This study was aim to investigate the factors affecting HIV progression to AIDS so as to identify the most important factors associated with accelerating conversion of infection to disease. This historical cohort study was conducted on the individuals infected with HIV in Fars province, south of Iran during 2006 to 2013. The study data were obtained using the information documented in the patients' records. For statistical analysis, first t-test, f-test, and Pearson's correlation coefficient were used as univariate analysis and then, log linear or Poisson regression were applied as multivariate analysis. The study findings indicated that variables, such as female gender, unemployment, addiction, joint injection, joint blade use, HIV infection via injection or sex, longer durations, and older ages, could play the role of risk factors for HIV progress. On the other hand, some variables, including insurance coverage, receiving TB prophylaxis, receiving HAART, and higher baseline CD4 cell count, could act as protective factors and decelerate the trend of disease progress. Many factors affect CD4 cell count in HIV patients. Some of these factors, such as gender, are irreversible, but some others, such as addiction, are preventable. As a result, special attention should be paid to these factors to slow down the process of HIV conversion to AIDS.