The aim of this paper is to compare the time to a viral load <50 copies/mL of three or four antiretroviral therapy (ART) regimens among ART naïve patients within the first 16 weeks after the start of treatment. A retrospective study was carried out on ART naïve patients who started HAART between 1 January 1999 and 1 January 2004. ART naïve patients with a viral load >5.3 log10 copies/mL at the time of treatment were routinely started on four ART regimens in one of the HIV centres in Edinburgh. These patients were compared with ART naïve patients with viral load >5.3 log10 copies/mL at the time of start of three ART regimens in the other centre within the study period. During the study period, of 93 ART naïve patients with a viral load >5.3 log10 copies/mL, 56 and 37 commenced four drug and three drug regimens, respectively. Patients in each group were matched for their age, prevalence of HCV, median age, and median viral load at the start of therapy; however, patients on three drug regimens had significantly lower CD4 counts (P<0.01). The median time to undetectable viral load was 13.5 weeks for three and four drug regimens (P>0.05). By the time of undetectable viral load, there was no difference in the CD4 count of patients on three or four drug regimens. Similar proportions of immunosuppressed patients on three and four ART regimens had undetectable viral load within the first 16 weeks of therapy.