This is due on the fact that ART targets virus entry or the viral enzymes, but not the integrated provirus.

Therefore, ART requires lifelong treatment, potentially leading to problems of cost (Chen et al., 2006 and Schackman et al., 2006), adherence (Mannheimer et al., 2002 and Paterson et al., 2000), drug resistance (Little et al., 2002 and Richman, 2006) and toxicity (Dybul et al., 2002). Particularly, long-term treatment frequently results in secondary complications, such as diabetes, hyperlipidemia, cardiovascular disease, osteoporosis, and chronic kidney disease (Calmy et al., 2009 and Deeks and Phillips, 2009). More importantly, patients successfully treated with ART for several years still do not fully recover their immune responses, and show increased levels of immune

activation BLZ945 along with its harmful effects (Ostrowski, 2010 and Plana et al., 1998). Consequently, low-level viral replication may persist along with an established pool of latently infected cells (Finzi et al., 1997, Finzi et al., 1999 and Palmer et al., 2008). When ART treatment is interrupted viral load can quickly rebound, even in patients who have suppressed plasma viremia to levels below detection limits for many years (Davey et al., 1999). Therefore, developing novel therapeutic strategies aiming to cure HIV infection must address the pool of cells that harbor the latent HIV reservoir (Chun and Fauci, 2012, Deeks et al., 2012 and Richman et al., 2009). In principle, two qualitatively different types of cure have been defined (Dieffenbach and Galunisertib Fauci,

2011, Lafeuillade, 2011 and Lewin et al., 2011). In a “functional cure” the patient’s immune defense fully controls HIV in the absence of ART. However, proviral DNA can still be found in the body. In contrast, a “sterilizing cure” eradicates HIV and no viral genes remain in the infected Rucaparib nmr host. Clearly, a functional cure may be easier to achieve, but a sterilizing cure is considered to be the holy grail of HIV therapy. The long-lived resting cells that contain HIV reservoirs reside primarily in tissues, in other words sanctuary sites that may not be easily accessible (Lafeuillade, 2012, Palmer et al., 2011 and Smith et al., 2012). The proviral DNA (i.e. the integrated replication-competent HIV genome) in these cells is transcriptionally silenced, mainly due to epigenetic modifications of the viral long terminal repeat (LTR) promoter region (Coiras et al., 2009, Geeraert et al., 2008 and Richman et al., 2009). Hence the viral antigens are not expressed, and in consequence, these HIV-infected host cells evade immune surveillance. Importantly, the existence of these viral reservoirs is believed to be the main hurdle to quantitatively clearing the virus from an infected organism.