Objective The rate of prevalence of HIV/AIDS among adults has been increasing in Sub-Sahara African countries over the last decade. Currently, an estimated number of 722, 248 people are living with HIV, 23, 000 people are newly infected with HIV and 11,000 people are died because of AIDS related illness. The purpose of this study was to identify the most significant variables associated with the variation of CD4 cell count and body mass index (BMI) of HIV positive adults who initiated HAART at Felege Hiwot Teaching and Specialized Hospital, North-West Ethiopia. Methods To analyze the long-term CD4 cells count and body mass index of HIV infected adults, a prospective follow-up study of 792 HIV-infected patients was performed. A joint model was employed to identify the variables associated with the variation of CD4 cell count and body mass index of adults receiving HAART. A random of 792 samples was taken among charts in the hospital. Results Among the main effects, Socio-demographic variables (Level of education, level of exposedness of disease to persons living together, Marital status and residence area), individuals characteristics (age and weight), economic factors (ownership of cell phone, level of income), clinical factors (baseline CD4 cell count), level of retention (time to follow ups, food and medical adherence) and economic factors(owner of cell phone) significantly affected the variables of interests. Similarly, the interaction effects of time of follow-up visits * cell phone ownership, follow-up visits * gender, age * sex significantly affected both response variables through a linear link function in current investigation. Conclusion Socio-demographic, individual and Clinical variables had significant effect on CD4 cell count and BMI in HAART medication program. Time to follow ups in the HAART program had also direct and significant effect on the variables of interest.