Human immunodeficiency virus (HIV) is a global epidemic with 35 million people living with HIV/AIDS worldwide, the majority of whom reside in resource-poor countries. By 2012, sub-Saharan Africa accounted for 70% of the universal total, with South Africa home to the largest number of people living with HIV in the world (6.1 million) .
The roll out of antiretroviral therapy (ART) has profoundly improved the grave portrayal of this disease in South Africa. The national ART program commenced in 2004 and the latest WHO statistics show that, at the end of 2012, there were an estimated 2 150 881 HIV-infected people receiving ART in South Africa . However, while ART prolongs the lives of HIV-infected individuals , it is associated with a variety of metabolic sequelae, including metabolic abnormalities and morphological body changes [3–5], that may adversely affect quality of life with long-term use . There is, therefore, a growing need to understand the impact of ART use and on health-related quality of life (HRQoL).
Numerous studies have examined HRQoL in HIV-infected individuals the impact of ART on HRQoL in HIV infected adults in South Africa [7–12]. These studies have been either cross-sectional or longitudinal designs. A recent cross-sectional study demonstrated a significant association between ART use and improved HRQoL indicators . A second cross-sectional study found an improvement in physical health only . Another study showed less pain and discomfort and fewer problems with self-care, daily activities and general mobility . In addition, longitudinal studies have shown significant improvements in HRQoL during 7 months , 12 months  and 24 months  of follow-up after ART initiation.
There are, however, relatively fewer studies from South Africa that assessed the effect of higher CD4 cell counts on HRQoL [7, 13]. Bhargava and colleagues  found the HRQoL of patients receiving ART increased significantly with improvement in CD4 count . Igumbor and colleagues  found weak but significant associations between CD4 cell counts and HRQoL in a cohort of treatment-naïve patients and those who had received ART for 12 months.
Globally, there has been concern about how ART-related toxicities may adversely affect HRQoL of HIV-infected individuals. Non-nucleotide reverse transcriptase inhibitors such as stavudine (d4T) have been shown to be associated with metabolic complications such as dyslipidemias, lipoatrophy, peripheral neuropathy and lactic acidosis [14–25]. Owing to toxicity concerns, the World Health Organization (WHO) in 2010 recommended the replacement of d4T with tenofovir (TDF) or zidovudine (AZT) -based first-line regimens which have better safety profiles [26, 27].
Despite the World Health Organization recommendation to phase out d4T, the national ART programs of South Africa and other developing countries continue to use d4T as part of their first-line ART regimen. By the end of 2011, 1.1 million people were taking d4T regimens globally, the vast majority in resource limited settings in sub-Saharan Africa . Progress in phasing-out d4T has been tampered by the higher cost of the alternative drugs AZT and TDF, uncertainties regarding whom to give priority to for phase out, the existence of stockpiles of d4T in several countries  and the failure of major donors to support the complete elimination of d4T . With the lack of full elimination of d4T from first-line regimens in resource-poor countries, there is a need for studies on the impact of d4T-containing first-line ART regimens on HRQoL in order to inform their national ART programs.
Therefore, the objectives of this study were to establish whether there was a difference in the HRQoL in those patients who were not receiving ART compared to those who were on first-line ART (predominantly d4T-containing regimen for longer than 6 months) in public sector treatment program in Cross roads, Cape Town, South Africa. In addition, we aimed to examine the relationship between ART status and HRQoL according to CD4 count strata.