Objective:To study the antiviral effect and predictors of response to two- and three-drug regimens amongst antiretroviral-naive individuals using an intent-to-treat analysis.Main outcome measure:Suppression of plasma viral load to <500 copies/ml.Patients:A total of 420 (264 double drug, 156 triple drug) individuals in a province-wide treatment programme were studied.Results:A decrease in plasma viral load to < 500 copies/ml was documented in 197 (47%) subjects. This was independently associated with a lower baseline plasma viral load (odds ratio, 3.67; 95% confidence interval, 2.13–6.30) and initiation onto a three-drug regimen (odds ratio, 3.86; 95% confidence interval, 2.24–6.66). Median plasma viral load failed to reach < 500 copies/ml and in fact rebounded in the two-drug group. In contrast, 91 (58%) subjects receiving three drugs reached <500 copies/ml during the study period.Conclusion:These results support the use of powerful triple drug regimens as initial therapy in HIV-infected individuals.