**2. HAART as a new perspective of life for HIV+ subjects**

For HIV-1-infected patients, the 1990s were marked by the introduction of HAART, which represented a new perspective of life for these patients [1]. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity rates, which has led to a better and longer quality of life for HIV-1 patients [2]. The HAART regimens, composed of at least three different antiretroviral drugs, are effective in reducing viral load (HIV-1-RNA) to undetectable levels when adhered to recommend‐ ed prescription [3]. HAART regimens, with their different combination of drugs, inhibit viral replication by acting at different stages of infection [4]. This allows them to reach the viral cycle and/or viral enzymes and thus are classified in different therapeutic groups according to their mechanism of action: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, entry inhibitors (CC chemokine receptor-5 [CCR5] antagonists), and integrase strand transfer inhibitors (InSTIs) [5-10] (Table 1). NRTIs are nucleoside and nucleotide analogues which inhibit reverse transcription during HIV-1 infection. HIV-1 is a virus that has RNA as the genetic material, and is unable to integrate its DNA into host cell. For its integration into the chromosomal DNA of the human cell it must be reverse transcribed into DNA by a reverse transcriptase. The conversion of RNA to DNA therefore, is made by the viral protein reverse transcriptase (RT). NRTIs prevent reverse transcriptase's enzymatic activity and block completion of synthesis of the double-stranded viral DNA, this prevents HIV-1 multiplication. They are analogues of naturally occurring deoxynucleo‐ tides and competitively incorporates itself into the growing chain of viral DNA. NRTIs lack a 3′-hydroxyl (3 'OH) group on the deoxyribose moiety thus act as a chain terminator which prevents the next deoxynucleotide from forming another 5′–3′ phosphodiester bond needed to extend the DNA chain [5]. NNRTIs inhibit RT by binding to an allosteric site of the enzyme, and act as non-competitive inhibitors of RT. NNRTIs as a class of drug affect the handling of substrate (nucleotides) by RT by binding near the active site [6]. PIs on the other hand block the viral protease enzyme necessary to produce mature virions upon budding from the host membrane; ultimately these drugs prevent the cleavage of gag and gag/pol precursor proteins. In the presence of protease inhibitors, virus particles pro‐ duced are defective and mostly non-infectious [7]. Fusion inhibitors and entry inhibitors interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. The drugs selzentry and enfuvirtide are the two currently available agents in this class. Selzentry works by targeting CCR5, a co-receptor located on human helper T-cells. Enfuvirtide is a peptide drug that must be injected and acts by interacting with the Nterminal heptad repeat of gp41 of HIV-1 to form an inactive hetero six-helix bundle, which prevents infection of host cells [8, 9]. InSTIs, also known as integrase inhibitors, inhibit the viral enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors currently under clinical trial; the drug raltegravir became the first to receive United States (US) Food and Drug Administra‐ tion (FDA) approval in 2007. Raltegravir has two metal binding groups that compete for substrate with two Mg2+ ions at the metal binding site of integrase. Two other clinically approved integrase inhibitors are elvitegravir and dolutegravir [10]. Apart from the great benefits of the use of different HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects on metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis [11-14]. However, other factors, such as virological, genetic, and individual immunological features, may be involved in the metabolic and lipid alterations observed because not all of the patients exposed to the same HAART regi‐ mens are affected [15-17].
