IntroductionThe identification, prevention, and clinical solution of drug interactions (DIs) are a critical aspect to achieve desired pharmacotherapy goals in patients infected with human immunodeficiency virus and/or affected by acquired immunodeficiency syndrome (HIV/AIDS) receiving antiretroviral (ARV) therapy, mainly because DIs may lead that ARV therapy will be unsafe and/or ineffective and thus, DIs may be clinical relevant.Additionally, in this group of patients the DIs are more frequent among other aspects by: The use of Highly Active Antiretroviral Therapy (HAART) or combined Antiretroviral Therapy (cART) includes three or more ARV drugs; (DHHS, 2011) therefore it is associated with a greater likelihood of DIs. The pharmacokinetic properties of ARV drugs, for instance several of them are metabolized through complimentary cytochrome P450 isoenzymes, thus their therapeutic use could be accompanied by frequent DIs.(Miller et al., 2007)  ARV drugs are concurrently used with other class of medications for other common conditions, mainly infections and cardiovascular disease; and many of these medications used to treat these conditions are metabolized through complimentary cytochrome P450 isoenzymes, so several pharmacokinetic DIs may occur.Accordingly, some studies illustrate that the 96% of patients receiving HAART or cART has at least a clinical condition or use a concomitant drug that could cause that ARV therapy may be unsafe (adverse drug reactions) or ineffectiveness (therapeutic failure).(Grimes et al., 30 2002) Therefore, identifying, preventing, and solving clinically relevant DIs is recognized both as a topic of great importance in achieving therapeutic goals for drug therapy (Kashuba, 2005) as a constant challenge to health care providers to HIV-infected patients receiving HAAR or cART.In addition, the clinical significance of a DI depends on the disposition and toxicity profile of the drug being administered.Thus, in HIV-infected patients assessing the clinical relevance of a DI is complex due to the large interpatient variability in pharmacokinetics exhibited by most ARV drugs, and then the evaluation and prediction of clinical effect of a DI is critical in the pharmacotherapy of patients with HIV/AIDS. www.intechopen.comUnderstanding HIV/AIDS Management and Care -Pandemic Approaches in the 21st Century 302 Since most of ARV drug DIs are clinically relevant, it is considered appropriate both to outline the concept, types, mechanisms, and effects of ARV DIs on drug therapy, and to present a comprehensive summary of those drugs that are affected and the clinical relevance of ARV DIs.In this way, the aim of this chapter is provide evidence and systematize information about DIs in HIV-infected receiving ART therapy, which allow define, evaluate, and predict the clinical relevance of the DIs, highlight those associated to pharmacokinetic mechanism.In this way, a proposal to identify, evaluate, and predict DIs considered as clinically relevant is presented, in which clinical relevance of a DI is defined according to the probability of their occurrence and to the severity of clinical effect in patient health (adverse event or therapeutic failure).(Amariles et al., 2007a) Previous review about DIs with ARV, (Amariles et al., 2007b;Giraldo et al., 2010) achieved as a result of searched in Pubmed/Medline database, have showed that, in the case of clinically relevant pharmacokinetic interactions, nearly 80% are related to changes in systemic clearance, mainly associated to the systemic inhibition or induction of the metabolic activity of the cytochrome P-450 (CYP-450), mostly CYP3A4 isoform, whereas approximately 15% are related to changes in bioavailability (changes in gastrointestinal pH, presystemic clearance [mediated by CYP3A4 hepatic or intestinal]) or in P-glycoprotein activity).(Amariles et al., 2007b;Giraldo et al., 2010) For this chapter, the earlier published information (Amariles et al., 2007a(Amariles et al., , 2007b;;Giraldo et al., 2010;Amariles, 2002.)have been complement with information achieved from both a structured and systematic review of publications on Pubmed/Medline and references cited in relevant articles, and in other electronic databases (SIETES, MEDSCAPE, and TRIPDATABASE), and supplemented by other primary and secondary information sources to identify DIs in HIV-infected patients.Thus, searched MeSH terms were drug interactions, antiretroviral agents (or drugs), drug food interactions, drug nutrient interactions, drug laboratory test interference, drug in special situations (age, diseases), drug herbal plant interactions, computerized drug interactions, decision clinical computer based, and clinical relevance, clinically relevant or significantly relevant.Finally, according with clinical relevance of the DIs, pairs of the identified DIs have been classified in four levels, according to rate probability and severity, (Amariles et al., 2007a(Amariles et al., , 2007 b; b;Giraldo et al., 2010) and then, the different drug pairs have been structured in a software designed to facilitate the identification, evaluation, and prediction of clinical relevant DIs.Current, 1,082 drug pairs of potential DIs have been identified, near to 80% of them due to pharmacokinetic mechanism (changes in plasma concentration), mainly associated to systemic enzyme inhibition.The scaling of these 1,082 drug pairs of recognized DIs, according to different dosage forms and strengths of identified drugs, generates a total of 6,087 pairs of DIs, in which, according their clinical relevance, 4,158 (68.3%) are clinical relevant (Levels 1 and 2) in HIV-infected patients receiving ARV therapy.Thus, the designed software meets the requirements defined for this type of program (Gaikwad et al., 2007;Rodríguez et al., 2009) and most important it facilitates the assessment, prediction, and decision on clinical relevance of 4,158 ARV DIs, which are considered of clinical interest in patients with HIV/AIDS (levels 1 and 2). Drug interactions in HIV-infected patients receiving antiretroviral therapy2.1 Concept, type, and mechanism of drug interactions Concept of DI.In patients with HIV/AIDS a DI could be assumed as non-therapeutic and quantitative modification in the magnitude or duration of the drug effect (decrease the www.intechopen.com