The search for new ways to improve treatment of patients infected with HIV is constant. Considering the experience that has been gathered since the 1980s of ARV drug development arrival of INSTIs as a new potent class of ARV signals a new era in the treatment of HIV. Development of a successful INSTI treatment was accomplished when raltegravir was discovered by Merck Sharp & Dohme Limited. A conditional marketing authorization was licensed in December 2007 by the European Commission which was valid throughout the European Union. In 2009 this authorization was converted to a full marketing authorization and in the same year the FDA changed the approval from accelerated to traditional approval and listed the drug as a first line ARV treatment agent.  The second INSTI drug, elvitegravir, was identified by Japan Tobacco and clinical trials began in 2005. In 2011 the drug was still in phase three clinical trials, where it is being compared to raltegravir, in treatment experienced subjects and is also in phase two development in naïve subjects as a part of a multidrug treatment. S/GSK1349572 is an integrase inhibitor discovered by ViiV/Shinongi which was entering phase three in clinical trials in 2011. This new drug is promising and seems to be well tolerated and so far shows better results than both raltegravir and elvitegravir.
Since there have been problems with resistance to raltegravir and elvitegravir, scientists have started to work on new second generation integrase inhibitors, such as MK-2048 which in 2009 was developed by Merck. It's a prototype second generation INSTI that remains potent against viruses containing mutations against raltegravir and elvitegravir. The mechanism of action and SAR of MK-2048 is the same as of the other INSTIs, the structure of MK-2048 shown in figure 6 with essential pharmacophore highlighted.
Even though drugs discussed above are promising the development has a long way to go and many things are still unknown about the efficacy, safety and mechanism of action of these drugs.