Background: CD4 count and body weight in Human Immunodeficiency Virus infected patients is an important component in assessing progress and response to therapy and clinical judgment. CD4 count is commonly used in resource limited settings where viral load measurements are not routinely done. Weight loss and low CD4 count has been reported as predictors of morbidity and mortality among adults infected with Human Immunodeficiency Virus. Studies have shown contradictory information about the factors associated with weight and CD4 count changes among patients infected with Human Immunodeficiency Virus. Objective: The aim of this study is to assess factors associated with changes in weight and CD4 count among Human Immunodeficiency Virus patients on highly active antiretroviral therapy at Kibong’oto Hospital. Methodology: It was a retrospective cohort study using routine data from Human Immunodeficiency Virus care and treatment clinic at Kibong’oto Infectious Disease hospital. Data were extracted from care and treatment clinic database. Patients infected with Human Immunodeficiency Virus started on highly active antiretroviral therapy from 2005 to December 2013were included. Mixed models regression was used to assess factors associated with changes in body weight and CD4 count. Results: At a time of antiretroviral therapy initiation median CD4 counts was 117cells/mm3. Patients started on antiretroviral therapy experienced progressive increase in CD4 counts of and body weight for the first 30 months of treatment. Duration of highly active antiretroviral therapy was an important factor associated with changes in body weight and CD4 counts beta coefficients 4.95, 95% CI 3.99 – 5.92, p value <0.001 and 0.08 ,95% CI 0.07 – 0.09, p value <0.001 respectively. Conclusion: Patients started on highly active antiretroviral therapy should be encouraged to continue with the treatment and there should be efficient mechanisms of tracing the lost to follow up patients at Kibong’oto hospital. Reasons for lower median CD4 count at baseline need further investigation.