PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.
BACKGROUND
Microbicides used to prevent the transmission of human immunodeficiency virus (HIV) are advancing to clinical trials on the basis of activity observed in vitro and in animal models. However, no data demonstrate activity of microbicides after application in humans. This study was designed to determine the antiviral activity in cervicovaginal lavage (CVL) samples collected after intravaginal application of 0.5% PRO 2000 gel (Indevus).


METHODS
A randomized, double-blind study was conducted to assess the anti-HIV and anti-herpes simplex virus (HSV) activity of PRO 2000 in CVL samples obtained at screening (48 hours before) and 1 hour after application of study or placebo gel. HeLa cells or human macrophages were inoculated with CVL samples spiked with replication-defective HIV containing a luciferase indicator gene and pseudotyped with an R5 envelope. Human cervical epithelial cells were inoculated with CVL samples and challenged with HSV-2(G), and the virus titer was then determined.


RESULTS
CVL samples obtained after application of PRO 2000 gel significantly inhibited HIV and HSV infection by at least 1000-fold, compared with CVL samples obtained at screening (P < .001). There were no differences in cytokine levels between the drug and placebo groups.


CONCLUSIONS
PRO 2000 gel (0.5%) is sufficiently bioavailable and retains substantial antiviral activity after intravaginal application. This strategy provides a mechanism for testing the efficacy of a microbicide before embarking on large-scale clinical trials.
Keller
Marla J
MJ
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Zerhouni-Layachi
Bouchra
B
Cheshenko
Natalia
N
John
Minnie
M
Hogarty
Kathleen
K
Kasowitz
Andrea
A
Goldberg
Cindy L
CL
Wallenstein
Sylvan
S
Profy
Albert T
AT
Klotman
Mary E
ME
Herold
Betsy C
BC
D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D002460:Cell Line; D002584:Cervix Uteri / Q000821:virology; D004311:Double-Blind Method; D005260:Female; D005782:Gels / Q000008:administration & dosage*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects; D006367:HeLa Cells; D006561:Herpes Simplex / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000821:virology; D008875:Middle Aged; D009282:Naphthalenesulfonates / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D007507:Therapeutic Irrigation; D016896:Treatment Outcome; D014621:Vagina / Q000821:virology
D000998:Antiviral Agents; D005782:Gels; D009282:Naphthalenesulfonates; C120231:PRO 2000; D011108:Polymers