ABSTRACT
Human immunodeficiency viruses (HIV) produce several enzymes, among them integrases which provide the integration of the viral genetic material into the deoxyribonucleic acid (DNA) of the infected cell, being thus the essential part in the pre-integration complex. Viral integrase was considered an attractive and promising target for therapy: HIV viruses are not able to replicate without integration into a host chromosome. Tetramer HIV-integrase models lead to reasonable mechanisms for trans-binding of viral DNA and concerted integration of both viral ends to host DNA. The first HIV-integrase inhibitor approved by the frequency-dependent attenuation is raltegravir, derived from the evolution of 5,6-dihydroxypyrimidine–4-carboxamides and N-methyl–4-hydroxypyrimidinone-carboxamides. Elvitegravir is also a first generation HIV integrase inhibitor, recommended in HIV infection treatment in combination with a pharmacokinetic booster, suitable in a single daily dose administration. Dolutegravir is an orally administered HIV-1 integrase strand transfer inhibitor suitable for an unboosted once-daily therapy used in combination with other retroviral agents in the HIV-1 infection treatment.
