title: HIV type 1 integrase inhibitors: from basic research to clinical implications.
abstract: Similar to other retroviruses, productive infection with HIV-1 requires three key steps in the viral replication: (i) reverse transcription of viral genomic RNA into viral cDNA by the viral reverse transcriptase; (ii) integration of viral cDNA into host cell genome using the viral integrase; and (iii) cleavage of newly synthesized viral polypeptide by the viral protease into individual viral proteins during new virion assembly. Following their discovery, all three viral enzymes were considered as targets for antiretroviral drugs. However, while multiple reverse transcriptase and protease inhibitors have been used for more than 12 years to treat HIV-infected individuals, only recently has the viral integrase enzyme emerged as an alternative, clinically validated target to block HIV-1 replication. Here we review the biology of HIV-1 integration, the mechanisms of action and development of resistance to integrase inhibitors, and the latest data on the most recent clinical trials involving this promising, novel class of antiretroviral drugs.
authors.affiliation: Department of Cellular and Molecular Biology, Kent State University, Kent, Ohio, USA.
authors.forename: Oyebisi
authors.initials: O
authors.lastname: Jegede
authors.forename: John
authors.initials: J
authors.lastname: Babu
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.forename: Damian J
authors.initials: DJ
authors.lastname: McColl
authors.forename: Jan
authors.initials: J
authors.lastname: Weber
authors.forename: Miguel
authors.initials: M
authors.lastname: Quiñones-Mateu
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D016896:Treatment Outcome; D016662:Virus Integration / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase