In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides.
The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission. Both drugs had a favorable therapeutic index. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV.
Van Herrewege
Yven
Y
Laboratory of Immunology, Institute of Tropical Medicine, Antwerp, Belgium. yvherrewege@itg.be
Michiels
Jo
J
Van Roey
Jens
J
Fransen
Katrien
K
Kestens
Luc
L
Balzarini
Jan
J
Lewi
Paul
P
Vanham
Guido
G
Janssen
Paul
P
D000813:Anilides / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002474:Cell-Free System; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005663:Furans / Q000494:pharmacology*; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1; D006801:Humans; D011743:Pyrimidines / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013854:Thioamides
D000813:Anilides; D019380:Anti-HIV Agents; D005663:Furans; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013854:Thioamides; C100668:UC-781; C481671:Dapivirine