To systematize information about drug interactions in HIV/AIDS, and to test a proposal to identify and evaluate drug interactions considered clinically relevant highlight those associated to pharmacokinetic mechanism.We performed a MEDLINE search of the literature published in English and Spanish from January 1995 to June 2007 on antiretroviral drug interactions in humans. Search terms were drug interactions and antiretroviral agents (or drugs) in title/abstract field. So, we searched for clinically relevant drug interactions of specific drugs commonly administered to patients with HIV, and we reviewed references cited in relevant articles. Finally, we followed a proposal to evaluate and use the clinical relevance complemented with a classification based on severity and probability of its occurrence.A total of 378 articles were achieved, among then we acquire the full text of 296. We presented the type and mechanism of drug interactions in HIV-infected patients. We evaluate and use the clinical relevance of drug interactions. Among pharmacokinetic interactions considered clinically relevant, approximately to 80% was related to changes in systemic clearance [due to induction or inhibition of systemic metabolic activity of cytochrome P450 3A4 (CYP3A4)]; and 15% with changes in bioavailability [(due to changes in gastrointestinal pH, presystemic metabolism or activity of the glicoprotein -P (Gp-P)].Among patients with HIV/AIDS, most of the pharmacokinetic interactions of clinical relevance are attributed to inhibition or induction of hepatic systemic metabolic activity, mainly of CYP3A4.