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This study aimed to investigate the health related quality of life (HRQoL) of people living in lower socio-economic areas comparing HIV positive on anti-retroviral treatment (ART) and HIV negative respondents and investigating the factors associated with their HRQoL. In total 600 respondents in eThekwini, KwaZulu-Natal were included from both phase one (household sample) and phase two (clinic sample). The Euro Quality of life (EQ 5D) instrument and the Visual Analogue Score (EQ-VAS) were used. The majority of the respondents (79.0 %) were females, and those who were HIV positive on ART were younger than those who were HIV negative, mean age [34.8 years (8.85 SD) vs. 37.1 years (14.65 SD; HIV negative females; p = 0.02)]. Males with a higher perceived quality of health-score [50 % were two and a half times more likely to have attended high school and to experience no pain/discomfort when compared to those reporting pain/ discomfort (OR 0.32, 95 % CI 0.16, 0.64). The odds of females reporting problems with their mobility and usual activities compared to no such problems, were associated with lower EQ VAS scores [OR 2.10 (1.20, 3.67) and OR 2.22 (1.21, 4.08)], respectively. For both HIV positive respondents on ART and HIV negative respondents living in lower socio & Prishah Narsai