Antiretroviral (ARV) therapy against HIV has greatly decreased the AIDS mortality rate which in turn has led to HIV being considered as a chronic disease for adults and children, requiring life-long therapy. Despite the availability of different classes of ARV agents providing a variety of treatment options, treatment failure continues to occur because of ARV drug resistance, drug-associated toxicity and tolerability problems, and poor adherence. New therapies should aim to be convenient and have favourable tolerability and safety profiles to provide alternative treatment options in children and adolescents. In particular, there is a need for new therapies for multi-drug resistant (MDR) paediatric patients, who by definition have failed multiple ARV classes/regimens, have very few remaining therapeutic options, and are often on ARV combinations that are highly individualised and may lack efficacy, safety and tolerability profiles of agents traditionally used in earlier lines of therapy.