Human immunodefiency virus (HIV) infection can be effectively treated with highly active antiretroviral therapy (HAART); requiring concomitant administration of three to four different agents; often with a high potential for drug-drug interactions (DDIs). This study aimed to determine the prevalence of possible DDIs between antiretrovirals (ARVs) themselves and other drugs. Design. Retrospective drug-utilisation study using data from from a national medicine claims database for the period 1 January to 31 December 2004. Setting. A section of the private healthcare sector in South Africa. Subjects. All ARV prescriptions (N=43482) claimed during 2004. The possible DDIs found were classified according to a clinical significant rating as described by Tatro7 (2005) in his book; Drug Interactions Facts and comparisons. Results. A total of 5305882 medicine items were prescribed; of these; 1.92(N=101 938) accounted for ARVs. Of the total number of 2595254 prescriptions; 1.68(N=43 482); were ARVs. A total number of 18035 DDIs (81 different types) were identified; of these; 83.89; (n=15130) were DDIs between ARVs and other drugs; while 16.11(n=2905) were DDIs between ARVs themselves. Possible DDIs with a clinical significance level of 1 (major; n=17) and 2 (moderate; n=1436) represented 8.06(n=1 453) of the total number of identified interactions. Conclusions. Since concomitant use of ARVs and other drugs used to treat HIV complications is increasing; there is a great need of understanding and anticipating these DDIs; overcoming them by dose adjustments and patient education by pharmacists; so that they are not life threatening to HIV/AIDS patients