KwaZulu-Natal province, South Africa, accounts for 28.7% of the HIV infection total and one-third of infections among youth and children in South Africa. The purpose of this study was to examine the variables of HIV/AIDS symptoms, social support, influence of comorbid medical problems, length of time adhering to antiretroviral therapy medications, quality of life, adherence to antiretroviral medications, and physical functioning in HIV-infected individuals. Based on our model, the combination of these variables was found to determine physical functioning outcomes and adherence to HIV medications. Significant relationships were observed between physical functioning and the dependent variables of length of time on medications, comorbid health problems, and social support. A linear regression model was built to determine the degree to which these variables predicted physical functioning. In total, these predictor variables explained 29% of the variance in physical functioning. These results indicate that those individuals who reported a greater length of time on medications, fewer comorbid health problems, and greater social support had better physical functioning.