title: Reverse transcriptase inhibitors as microbicides.
abstract: The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.
authors.affiliation: Pater Van Mierlostraat 18, B-2300 Turnhout, Belgium. paul.lewi@hotmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Lewi
authors.forename: Jan
authors.initials: J
authors.lastname: Heeres
authors.forename: Kevin
authors.initials: K
authors.lastname: Ariën
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Venkatraj
authors.forename: Jurgen
authors.initials: J
authors.lastname: Joossens
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D044966:Anti-Retroviral Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005782:Gels; D015658:HIV Infections / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D011323:Primates; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D044966:Anti-Retroviral Agents; D005782:Gels; D018894:Reverse Transcriptase Inhibitors