Although the world has been fighting HIV disease in unity and patients are getting antiretroviral therapy treatment, HIV disease continues to be a serious health issue for some parts of the world. A large number of AIDS-related deaths and co-morbidities are registered every year in resource-limited countries like Ethiopia. Most studies that have assessed the progression of the disease have used models that required a continuous response. The main objective of this study was to make use of appropriate statistical models to analyze routinely collected HIV data and identify risk factors associated with the progression of the CD4 + cell count of patients under ART treatment in Debre Markos Referral Hospital, Ethiopia. In this longitudinal retrospective study, routine data of 445 HIV patients registered for ART treatment in the Hospital were used. As overdispersion was detected in the data, and Poisson-Gamma, Poisson-Normal, and Poisson-Gamma-Normal models were applied to account for overdispersion and correlation in the data. The Poisson-Gamma-Normal model with a random intercept was selected as the best model to fit the data. The findings of the study revealed the time on treatment, sex of patients, baseline WHO stage, and baseline CD4 + cell count as significant factors for the progression of the CD4 + cell count.