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Background: With recent progress in the treatment of people living with HIV (PLWH) and their increased rate of survival, health-related quality of life (HRQoL) has become an important issue., Objective: In the present study, we aimed to investigate the association of current CD4 cell count, baseline CD4 cell count, nadir CD4 cell count, and plasma viral load with health-related quality of life in PLWH., Methods: Participants were 67 PLWH who were under the treatment of antiretroviral therapy (ART) in Imam Khomeini Hospital of Tehran, Iran in 2016. Participants were divided into the two groups with high and low levels of current CD4 cell count, baseline CD4 cell count, nadir CD4 cell count and plasma viral load. We used independent sample t-test for data analysis using SPSS 22 software., Results: Our results demonstrated that for current CD4 cell count, the group differences were significant for total scores of HRQoL (P=0.028), also in the components of physical functioning (P=0.032), role limitation due to physical health problems (P=0.006), and role limitation due to emotional problems (P=0.009). Our data analysis showed that for baseline CD4 cell count (P=0.62), nadir CD4 cell count (P=0.29), and viral load group (P=0.78), the differences were not significant for HRQoL., Conclusion: Knowing the association between current CD4 count and health-related quality of life, adherence to ART might be a motivator for PLWH to enhance their health-related quality of life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)