OBJECTIVES: Identify the most significant predictors affecting the quality of life (QOL) of persons living with HIV (HIV Persons) in a big city. METHODS: There was conducted three-stage study. At the first stage HIV morbidity and mortality follow up indicators of the HIV Persons who is living in megalopolis (Astana) were analyzed in comparison with the republican indicators for the 10 years period (2004-2013). At the second stage through the use of earlier developed by our force questionnaire, which is including 49 questions. At the third stage the QOL of HIV-infected persons was studied. The SF-36 questionnaire was chosen as the main tool for QOL research. The selection sample size hasincluded 170 respondents.   RESULTS: It was found that HIV-infection morbidity indicators of the capital city were significantly lower than the countrywide indicators. Despite the stick-slip nature, a morbidity steady growth was marked, then that rate stabilized and became1.11 per 100 000 of population in 2013. Comparison of QOL indicators by gender in relation to the majority of the scales of physical health component (PHC) as well as the total PHC in general revealed that men QOL indicators were higher than women QOL indicators. In the meantime the mental health component (MHC) indicators in relation to the total MHC and to the most scales were higher in women, but statistical differences between all scales were not significant (p> 0.05). Comparison of QOL indicators showed no dependence on the time of the establishment of HIV status. It was found that the drug use significantly reduces the QOL. CONCLUSIONS: Results of the study revealed the multivalued role of predictors that influence the quality of life of persons living with HIV in a big city. HIV morbidity risk reduced factors allow to carry out practical recommendations on the prevalence of the disease containment.